An Annotated Bibliography of Scientific Articles on AIDS for Policymakers Prepared for Office of the Assistant Secretary for Health Health Planning and Evaluation U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE ERVIC Sh 5 \ I \” = Se) po, ZW 4 [ brs 7 DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Office of the Assistant Secretary for Health Washington DC 20201 Dear Colleague: The challenge of acquired immunodeficiency syndrome (AIDS) is the number one health priority of this Department. To date, over 40,000 people in this country have been diagnosed with AIDS and over half of those diagnosed have died. We estimate that 1.5 million Americans are infected with the human immunodeficiency virus (HIV) and that many of these individuals will eventually develop AIDS or a related illness. As AIDS affects increasing numbers of the population, it will continue to be a growing concern to policymakers who are responsible for protecting the public health. Because AIDS is a new disease, development of scientific literature regarding the syndrome is rapid and diverse. For this reason, the Public Health Service initiated a project with Abt Associates, Inc. to provide a compendium of the many policy-relevant scientific studies on AIDS, as well as a listing of AIDS related resources available through Federal and State Government agencies, and public, private and voluntary organizations nationwide. I am pleased to present you with the result of this effort, An Annotated Bibliography of Scientific Articles on AIDS for Policymakers. I hope that this bibliography will provide you with a readily accessible and dependable resource for identifying the research literature available on AIDS. As we continue to challenge the course of AIDS, I am confident that by sharing our knowledge and making the best use of our resources, we will together conquer this disease. Sincerely, — A AE Ji bm Robert E. Windom, M.D. Assistant Secretary for Health Enclosure e ~ Ow X For sale by the Superintendent of Documents, U.S. Government Printing Office 8 Washington, D.C. 20402 SHI0077 X PYgL cu Submitted by: Abt Associates Inc. Principal Authors: Holly Korda Deborah Guiher Raymond Glazier Andrea Hassol Project Associates: Carol Aucoin Joshua Burditt, M.D. Debra Glazier Gary Levine, M.D. Cary Sennett, M.D. Deborah Welch Abt Associates Inc. 55 Wheeler Street, Cambridge, Massachusetts 02138-1168 Telephone «+ 617-492-7100 TWX: 710-3201382 , An Annotated Bibliography of - Scientific Articles on AIDS for Policymakers | July 1987 Prepared for: Office of the Assistant Secretary for Health Health Planning and Evaluation Sandra Bart, Project Officer This project was conducted under PHS Task Order Contract #282-85-0064 to "Provide Analysis and Problem-Focused Synthesis of Health Research Issues." An Equal Opportunity Employer TABLE OF CONTENTS PAGE Acknowledgements cevevssnvsssnsssevssenrvsvs cess saree TREES 1 INIrOdUCEION weve ssnessannevavusnssnssnnnes Sree RT NCTE vu ull Overview of the Document ......... vers Ran tase Rss rr anne veo How to Use This DOCUmMeNt « vovrsvsssrsessnnns sesunenssnsnwssIX Qutline of Policy Relevant Headings sv cvvevsvsrresnrvevvvsnnes Xl Bibliography cessive venss TL Ta IIT EEERERG RS RUS o 5 5 IXY Contents Of SECLIONS . ceveversersstnersvastssnerssssssnsrrsens xlix ADSLTACES vv verrssssvnsnsssisssnsssstssssssnosossveeas 1A1-Col-1 Policy Guidelines........ RRR wren ow won swum my veel] List of Abbreviations «.ssessscnss EAVES SE EIIRS GEOR ob G-1 GIOSSAIrY wussvvssnsrsovessnns 5 WHER DREN YS OE RE NO G-2 Resource Guide «vee eeeeeeeens HARES HORSES R-1 ACKNOWLEDGMENTS This resource document for policy makers has benefited from the contributions of a number of individuals and organizations whose assistance was crucial to the effectiveness and timeliness of this project and its publication. This project owes a special debt of thanks to Ms. Sandra Bart, Project Officer at the Office of the Assistant Secretary for Health (DASH). Ms. Bart has played a most significant role throughout, providing direction and valuable input to the project's focus and operations and facilitating achievement of project objectives. The resource document was initially conceived by Mr. James Friedman, Deputy Director, Office of Health Planning and Evaluation (OASH), Public Health Service, Department of Health and Human Services, who recognized the importance of having available to policy makers, in understandable and accessible form, the large body of research literature and programs that has accumulated in response to the challenge posed by the AIDS epidemic. The National Library of Medicine (NLM), Bethesda, Maryland, provided invaluable support and assistance throughout the project. Ms. Karen Patrias conducted extensive literature searches of various data bases, including MEDLARS, BIOSIS, EMBASE, PAIS, PSYCHINFO, SOCIAL SCISEARCH, Sociological Abstracts, NTIS, CATLINE, and LC Marc. Ms. Patrias, together with Ms. Eve Marie Lacroix, coordinated our use of their special article collection on AIDS topics, which includes a majority of AIDS journal articles published worldwide from 1983 through mid-1985. Review of early drafts was provided by individuals at the Centers for Disease Control, the National Institutes of Health, and NLM; we appreciate their comments and support. Review of a later version of this document was provided by individuals outside the Public Health Service with recognized expertise in AIDS policy and scientific research. Dr. Paul Volberding, Chief of Medical Oncology and AIDS Activity at San Francisco General Hospital and well-known authority on AIDS treatment, provided scientific review and input. Dr. Ronald Bayer, Associate for Policy Studies at the Hastings Center in New York, provided his assistance and expertise in policy-related areas. Dr. Roy Widdus, of the National Academy of Sciences, provided review of the glossary included in this volume, which is derived in part from the Institute of Medicine's recent publication, Confronting AIDS. Special recognition and appreciation also go to Ms. Christine Janson for her excellent technical editing and Ms. Mellen Candage at Grammarians, Inc., who facilitated the editorial production. This document was made possible by an awareness of the vital and urgent nature of the crisis AIDS has precipitated in the health community and among the general public and of the impact of this epidemic in human terms. Project staff especially wish to thank Ms. Deborah Welch for her tireless efforts in supervising word processing and production and Dr. Gary Levine and Dr. Cary Sennett of Abt Associates Inc. for their medical review and advice. ii INTRODUCTION This document was prepared as a resource for policy makers, to provide a cross section of the many policy-relevant studies conducted by the scientific research com- munity on acquired immune deficiency syndrome (AIDS)* in the United States and abroad. It also provides a listing of many of the resources available through federal and state government agencies and public, voluntary, and private organizations nationwide. The articles for which abstracts have been included cover a broad range of biomedical, epidemiological, educational, and economic topics from the published literature, appearing in scientific journals from January 1983 through December 1986. AIDS continues to be a growing priority for policy makers as the disease affects increasing numbers of the population; this resource document is intended to provide an information base to improve informed policy decision making. Great strides have been achieved in a variety of scientific disciplines since the AIDS problem was recognized in the spring of 1981 through reports to the Centers for Disease Control (CDC). The publication of three papers, from California and New York, in the New England Journal of Medicine in December 1981 established the disorder as a clinical entity. Close liaison was established that same year among Public Health Service agencies with major responsibilities for AIDS-related activities. The CDC initiated national surveillance and investigation in June 1981. These efforts have expanded to include support for health information education and risk reduction programs at the state and local levels. The Food and Drug Administration emphasized preventive measures related to blood collection and, more recently, has focused on the investigation of treatments and testing methods. The National Institutes of Health, through its intramural and extramural programs, mounted major basic research efforts on the funda- mental causes and clinical aspects of AIDS. A wide range of information and education - programs have been sponsored by the Alcohol, Drug Abuse and Mental Health Adminis- tration and are ongoing, and a series of AIDS-related demonstration projects and *The Human Retrovirus Subcommittee of the International Committee on the Taxonomy of Viruses has proposed the name human immunodeficiency virus (HIV) for the AIDS virus (Science 1986; 232:697). iid education and training centers are being supported by the AIDS program at the Health Resources and Services Administration. The combined efforts of French and American researchers led to the discovery of the etiologic agent of AIDS in the fall of 1983. A human retrovirus, in the human T- cell leukemia virus (HTLV) group, was identified as the cause of AIDS and named human T-cell lymphotropic virus type III (HTLV-II) in the United States and lymphadenopathy- associated virus (LAV) in France. By the fall of 1986 a common name was adopted for international use: human immunodeficiency virus (HIV). The process of scientific investigation and discovery, international in scope, has been marked by the committed efforts of individual investigators from interdisciplinary fields and by the support of their efforts by public, private, and voluntary funding sources. The dissemination of information generated by these efforts through the scien- tific and medical journals, as well as through conferences and symposia, has also played a significant role in the search for clues to unlock the enigma of AIDS. Formal research studies, clinical case reports, and letters of correspondence have all contributed signifi- cantly to the timely processing of hypotheses and evidence on such diverse topics as virus identification, clinical presentation, prevalence and incidence of disease, efficacy of therapies, education and risk reduction strategies, and animal models in the continuing search for a vaccine and cure for AIDS. Scientific journals play a crucial role in dissem- inating information within the research community. Informed policy making also rests on an understanding of the findings of scientific research. This document attempts to make this information accessible to nonscientific audiences and is intended to serve as a resource document and guide to these activities. iv OVERVIEW TO THE DOCUMENT Content This resource guide and bibliography was prepared with the assistance of several agencies, organizations, and individuals who have been actively involved with AIDS- related research and policymaking. Prepared by Abt Associates Inc. under contract with the Office of the Assistant Secretary for Health (OASH), the AIDS policy-coordinating agency for the U.S. Public Health Service (PHS), this document was developed to provide functional, relevant, comprehensive, detailed, and timely information about AIDS, written in lay terms and grouped under policy-relevant headings. Annotated references for the bibliography include a cross section of formal biomedical, epidemiological, and economic research studies related to AIDS which were published in the United States and abroad from 1983 through 1986. The document is organized around an outline prepared in summer 1986 by the PHS Executive Task Force on AIDS, a group which provides guidance and input to inter- agency programs and activities related to AIDS and human immunodeficiency virus (HIV) infection. Topics specified in this outline are considered by this group to represent areas of particular relevance to AIDS policy making. Outline headings and subheadings have been used to key each of the annotated references to primary, secondary, and tertiary subject areas and are listed at the end of each abstract. A cross-reference list is included at the beginning of this document to facilitate the identification of abstracts across topic areas. Criteria for Selection The research publications for which abstracts are included in this volume were selected from a much larger universe (over 10,000 articles have been published on AIDS and related topics). The National Library of Medicine (NLM) assisted with the identifica- tion of publications both by making available its special collection of published materials covering the period January 1983 through mid-1985 and by conducting extensive compu- ter searches of biomedical and social science data bases. These thousands of references were then screened by Abt Associates' project director and reviewed by project associ- ates to identify studies of particular relevance to policy-making audiences. Efforts were made to obtain and to abstract research articles representative of each bibliographic heading, although the available body of literature on each topic varies in quantity and content. It is inevitable that some materials are not included in this document due to the sheer volume of published articles, the somewhat subjective process of selecting specific and representative articles, and the rapid advances occurring in the scientific community and the policy-making arena. The broad scope of AIDS-related literature encompasses books, monographs, editorials, overview and summary works, conference abstracts, and letters of corres- pondence, in addition to published research studies appearing in scientific journals. Other published materials focus on the legal and ethical aspects of AIDS and HIV infection. While all of these sources might be considered for inclusion in a resource document developed for policy makers, this particular volume is limited to refereed journal articles that report scientific research findings. Readers who wish to use information available from other sources may refer to the resource listings in this document, for example, the NLM's quarterly listing of bibliographic references from MEDLARS, or the Centers for Disease Control's (CDC) routine surveillance reports, which many policy makers have found useful. An additional criterion for inclusion of study abstracts relates to sample size. Our selection process focused on including studies involving large numbers of subjects, as these studies generally report more robust findings, from many of the most significant, large-scale research efforts. However, many studies of particular policy importance which report important findings from study samples of much smaller size have been included. Studies reporting single-case findings have not been included due to the frequency of their appearance in the published literature and to avoid spurious conclu- sions that may be derived from early findings in one or more unusual cases. Findings such as these have played an important role in providing clues to emerging trends and breakthroughs in the search for knowledge about AIDS and should be considered in a thorough evaluation of policy options; but these studies, even considered selectively, are outside the scope and purpose of this document. We recognize that scientific discovery and investigation involve the contribu- tions and collaboration of and synthesis of work produced by many individuals and organizations -- generating ideas, scientific breakthroughs, and creating the knowledge base for science and policy -- and apologize for the omission of any articles of importance. It is important to note that some topics are more extensively covered than others, reflecting the status of research and published literature in these areas. Resea- rch on treatment for AIDS, for example, continues to develop and gain definition as vi scientific advances uncover new information in these areas on a daily basis. Many proto- cols and studies of therapeutic approaches are well under way, but await the test of time or greater numbers of subjects before formal results or conclusions can be reported. To obtain current, up-to-date information in areas such as these, the reader is asked to consult the resource directory in this volume, where the appropriate referrals and contacts are identified. Information is presented under three headings within each abstract: findings, methods, and sample size. Each of these categories contains relevant study data and is likely to vary somewhat across abstracts, depending on the disciplinary focus and format of reporting used by the authors and the journal in which the study appeared. We have attempted to maintain the format presented in each article in the abstracting process. We would like to direct the readers’ attention to entries in each category, since study findings reflect not only the methods used, but also the subjects selected for investi- gation. With some exceptions, routine surveillance articles, which increase in number as agencies and organizations worldwide increase efforts to monitor the spread of AIDS, have not been included. Surveillance is a significant activity, providing the basis for the epidemiological investigation of AIDS and HIV infection. Again, the reader is directed to the resource section of this document. The substantial contributions of the CDC to domestic and international surveillance are of particular note and may be identified through CDC's Morbidity and Mortality Weekly Report and specific reports prepared by the agency. A glossary of terms basic to an understanding of the basic science of AIDS and HIV infection, and relevant to the content of the abstracts, has been included as an additional resource. This glossary is based on the Institute of Medicine's glossary in their recent publication Confronting AIDS and has been expanded, with their permission, to reflect the content of abstracts in this volume. Resource Guide A listing of resource persons and programs in federal and state government has been included to provide policy makers with contacts from whom additional information may be obtained. This listing was compiled by OASH, based on information solicited for the project from its constituent agencies in the PHS. These organizations have been especially helpful in the preparation of this document and its companion, "Inventory of vii Scientific Research on AIDS and HTLV-III/LAV Infection," prepared for the CDC. The resource listing also includes several key organizations provided by the National AIDS Network, which maintains comprehensive listings of information, education and service organizations active in AIDS-related work across the country. While this resource listing is by no means comprehensive, it is intended to provide a starting point for the informa- tion-gathering process. Policy recommendations prepared by the PHS in areas of particular importance to AIDS and HIV infection, for example, infection control in occupational settings and blood product safety measures, are included in a special section of this document. These have been reprinted as they appeared in agency publications disseminated to the scientific community. Review The abstracts compiled in this document have been subjected to several phases of review, including review by two physician researchers at Abt Associates, as well as by Abt Associates' project director, and by principal staff; by PHS agency reviewers at CDC, NLM, OASH, and the National Institutes of Health, and by three external reviewers with expertise in editorial, scientific, and policy areas related to AIDS. Reviewers also assisted in the selection of abstracts relevant for inclusion. We appreciate their participation, support and commitment to the project. viii I. II. II. HOW TO USE THIS DOCUMENT Abstracts Each abstract provides the following summary information: all authors (princi- pal author first), the title of the article, the source journal information, and the authors' institutions of affiliation. A summary of findings, relevant aspects of the design and methodology, and demographic specifics of the sample, including dates and locations when available, are also provided. The "Policy Keys" listed at the end of each abstract are used to index abstracts to the outline of Policy- Relevant Headings at the beginning of the document. Abstracts are organized into sections of the document according to these keys, as explained below. Organization A. Sections Each section number corresponds to a section on the outline of Policy-Relevant Headings. Sections are referred to by roman numeral and letter (IIB) or by roman numeral, letter, and arabic numeral (IIIA4). Sections of the document are divided by blue pages showing the heading from the outline for that section. The seven dividers with tabs separate the major categories of the outline, [ through VII. Within each section, abstracts are ordered chronologic- ally, with the most recent articles first. B. Keys Each abstract has a list of one or more keys which correspond to the Policy- Relevant Headings in the outline. The abstracts are organized into sections according to primary key. For the remaining keys, the abstract is cross- referenced by "page number" (see below) in a list at the beginning of the document. Thus, for every section of the outline, all of the research studies in the document related to that topic are included either by an abstract or by a cross-reference to an abstract in another section. C. Pagination Page numbers represent the section in which the abstract appears, the first three letters of the principal author's last name, and the order of the abstract in that section. For example, 2A-Gaz-5 would be the fifth abstract in section IIA (Transmission: Sexual Activity) and have a principal author named Gazzard. How to Find an Abstract To assist in finding a desired abstract, two types of cross-reference lists have been included. The "Bibliography" and the "Contents of Sections" list appear at the beginning of the document following the Policy-Relevant Headings outline. The first is a full bibliographic reference for every abstract in the document, listed alphabetically by primary author and followed by the abstract's page number in the document. The second is an alphabetical list for each section of primary authors of abstracts in that section and of abstracts in other sections related to that topic, including the page number of each abstract. The left- ix hand column is the list of abstracts that can be found in that section; the right- hand column is the list of abstracts in other sections that include that topic in their keys, but not as the primary key. By using these two cross-reference lists, a particular abstract may be found either by author or by topic. PHS Executive Task Force on AIDS Policy Relevant Headings I. Prevalence and Spread of AIDS/HTLV-III/LAV A. Population Studies and Groups at Risk 2 4, Homosexual Males [.V. Drug Users Blood Product Recipients (Hemophiliacs, etc.) Pediatric Cases Minorities Heterosexuals Other a. Institutional (prisons, mental health, retardation, other) b. General Population Groups (blood donors, military recruits, random population, other) B. Geographic and Regional Trends i. 2. U.S. and Canada Caribbean/South America Australia Europe Africa Asia C. Cofactors } 2. Demographic Status (age, sex, ethnicity) Chemical or Drug Exposures (nitrites, other drugs, alcohol) Clinical Descriptors and Conditions (hepatitis B, Epstein-Barr virus, cytomegalovirus, HLA type) Other xi [I. Transmission Modes A. P 0 5 oO m m Sexual Activity [.V. Drug Abuse (shared needles) Blood Transfusion and Blood Products Perinatal Health Care Accidents Casual Contact Other [II. Characteristics of Disease A. B. C. D. E. F. Diagnostic Definitions and Clinical Manifestations of AIDS 1. Kaposi's Sarcoma 2. Opportunistic Infections 3. Diagnostic Indicators 4. Other Clinical Manifestations Precursors of AIDS and AIDS-Related Complex Incubation Period and Disease Stages Central Nervous System Disease Infection Immunological Aspects Other [V. Treatments for AIDS A. B. C. General Support Care Symptom Management Therapeutic Intervention I. Antiviral Therapy 2. Immunomodulators 3. Immune Reconstitution xii V. Risk Reduction A. Information/Education I. Public Awareness 2. Risk Behaviors and Protection B. Blood Product Safety 1. Screening Tests and Assays 2. Seroprevalence and Virus Isolation 3. Inactivation of Virus C. Infection Control in Occupational Settings VI. Related Policy Issues A. Intermediate and Long-Term Care B. Health Care Cost, Financing, and Payment C. Community Responses VII. Related Scientific Issues A. Animal Models for Retroviral Infections and Diseases B. New Virus Subtypes xiii BIBLIOGRAPHY Abb, J. "Evaluation of a New Confirmatory Assay for Antibodies against Lymphadenopathy-Associated Virus (LAV)/Human T-Lymphotropic Virus Type III (HTLV-II." Vox Sanguinis, 1986, Vol. 51: 233-235...... 5B1-Abb-3 Abrams, Donald I., Dobri D. Kiprov, James J. Goedert et al. "Antibodies to Human T- Lymphotropic Virus Type III and Development of the Acquired Immunodeficiency Syndrome in Homosexual Men Presenting with Immune Thrombocytopenia." Annals of Internal Medicine, January 1986, Vol. 104, No. 1: 47-50......3A4-Abr-2 Abrams, Donald [., Brian J. Lewis, Jay H. Beckstead et al. "Persistent Diffuse Lymphadenopathy in Homosexual Men: Endpoint or Prodrome?" Annals of Internal Medicine, June 1984, Vol. 100, No. 6: 801-808...... 3B-Abr-12 Aiuti, F., M.C. Sirianni, M. Carbonari et al. "IgM and IgG Antibodies to Human T Cell Lymphotropic Retrovirus (HTLV-II) in Lymphadenopathy Syndrome and Subjects at Risk for AIDS in Italy." British Medical Journal, 20 July 1985, Vol. 291, No. 6489: 165-166......1B4-Aiu-3 Allain, J.P. "SIDA, Syndromes Apparentes et Hemophilie: Situation en France et Etudes en Cours." Revue Francaise de Transfusion et Immuno-hematologie, 1984, Vol. 27, No. 4: 459-461...... 1A3-All-15 Allain, J.P., A.M. Courouce, J.Y. Muller et al. "Immunologic and Virologic Status of Multitransfused Patients: Role of Type and Origin of Blood Products." Blood, October 1985, Vol. 66, No. 4: 896-901...... 2C-All-9 Alter, Harvey J., Jorg W. Eichberg, Henry Masur et al. "Transmission of HTLV-III Infection from Human Plasma to Chimpanzees: An Animal Model for AIDS." Science, 2 November 1984, Vol. 226, No. 4674: 549-552...... 7A-Alt-7 Ammann, Arthur J., Lawrence Kaminsky, Morton Cowan et al. "Antibodies to AIDS- Associated Retrovirus Distinguish Between Pediatric Primary and Acquired Immunodeficiency Diseases." Journal of the American Medical Association, 7 June 1985, Vol. 243, No. 21: 3116-3118......] A4-Amm-4 Anderson, Kenneth C., Barbara C. Gorgone, Richard G. Marlink et al. "Transfusion- Acquired Human Immunodeficiency Virus Infection Among Immunocompromised Persons." Annals of Internal Medicine, October 1986, Vol. 105, No. 4: 519- 527 cavers 2C-And-1 Archibald, D.W., L. Zon, J.E. Groopman et al. "Antibodies to Human T-Lymphotropic Virus Type III (HTLV-II) in Saliva of Acquired Immunodeficiency Syndrome (AIDS) Patients and in Persons at Risk for AIDS." Blood, March 1986, Vol. 67, No. 3: 831-834......3F-Arc-1 Auerbach, David M., William W. Darrow, Harold W. Jaffe et al. "Cluster of Cases of the Acquired Immune Deficiency Syndrome: Patients Linked by Sexual Contact." The American Journal of Medicine, March 1984, Vol. 76: 487-492...... 2A-Aue-6 XV Ball, S.E., J.M. Hows, A.M. Worsley et al. "Seroconversion of Human T-Cell Lymphotropic Virus Type III (HTLV-II) in Patients with Haemophilia: a Longitudinal Study." British Medical Journal, 8 June 1985, Vol. 290: 1705- 1706...... 1lA3-Bal-9 Barin, F., F. Denis, J.S. Allan et al. "Serological Evidence for Virus Related to Simian T- Lymphotropic Retrovirus III in Residents of West Africa." The Lancet, 21/28 December 1985, Vol. 2, No. 8469/70: 1387-1389...... 7B-Bar-2 Barrett, Jean E., George Dawson, John Heller et al. "Performance Evaluation of the Abbott HTLV-III EIA, a Test for Antibody to HTLV-II in Donor Blood." American Journal of Clinical Pathology, August 1986, Vol. 86, No. 2: 180- 1854s00ee S5Bl-Bar-2 Bayley, A.C., R. Cheingsong-Popov, A.G. Dalgleish et al. "HTLV-III Serology Distinguishes Atypical and Endemic Kaposi's Sarcoma in Africa." The Lancet, 16 February 1985, Vol. 1, No. 8425: 359-361...... 3Al-Bay-5 Bayley, Ann C. "Aggressive Kaposi's Sarcoma in Zambia, 1983." The Lancet, 16 June 1984, Vol. 1, No. 8390: 1318-1320......3A1-Bay-6 Berthier, A., R. Fauchet, N. Genetet et al. "Transmissibility of Human Immunodefi- ciency Virus in Haemophilic and Non-Haemophilic Children Living in a Private School in France." The Lancet, 13 September 1986, Vol. 2, No. 8507: 598- 1 — 2F-Ber-1 Biberfeld, Gunnel, Blenda Bottiger, Anders Karlsson et al. "HTLV-II Infection in Homosexuals and Hemophiliacs in Sweden." Cancer Research, September 1985, Vol. 45 (Suppl.): 4609s-461 1s...... 2C-Bib-10 Biberfeld, Peter, Anna Porwit-Ksiazek, Blenda Bottiger et al. "Immunohistopathology of Lymph Nodes in HTLV-III Infected Homosexuals with Persistent Adenopathy or AIDS." Cancer Research, September 1985, Vol. 45 (Suppl.): 4665s-4670s...... 3C- Bib-10 Bigby, Timothy D., Dorothy Margolskee, Jeffrey L. Curtis et al. "The Usefulness of Induced Sputum in the Diagnosis of Pneumocystis carinii Pneumonia in Patients with the Acquired Immunodeficiency Syndrome." American Review of Respiratory Disease, 1986, Vol. 133: 515-518...... 3A3-Big-1 Biggar, Robert J., Mads Melbye, Luc Kestens et al. "Seroepidemiology of HTLV-III Antibodies in a Remote Population of Eastern Zaire." British Medical Journal, 16 March 1985, Vol. 290: 808-810...... 1B5-Big-6 Birx, Deborah L., Robert R. Redfield, Giovanna Tosato. "Defective Regulation of Epstein-Barr Virus Infection in Patients with Acquired Immunodeficiency Syndrome (AIDS) or AIDS-Related Disorders." The New England Journal of Medicine, 3 April 1986, Vol. 314, No. 14: 874-879...... 1C3-Bir-6 Bishburg, Eliahou, Gnana Sunderam, Lee B. Reichman et al. "Central Nervous System Tuberculosis with the Acquired Immunodeficiency Syndrome and Its Related Complex." Annals of Internal Medicine, August 1986, Vol. 105, No. 2: 210- 213... 3D-Bis-1 XV Blanche, S., F. Le Deist, A. Fischer et al. "Longitudinal Study of 18 Children with Perinatal LAV/HTLV-III Infection: Attempt at Prognostic Evaluation." The Journal of Pediatrics, December 1986, Vol. 109, No. 6: 965-970...... 3A2-Bla-1 Bloom, A.L. "Acquired Immunodeficiency Syndrome and Other Possible Immunological Disorders in European Haemophiliacs." The Lancet, 30 June 1984, Vol. I, No. 8392: 1452-1455...... 1A3-Blo-14 Blumenfeld, Walter, Elizabeth Wagar, W. Keith Hadley. "Use of the Transbronchial Biopsy for Diagnosis of Opportunistic Pulmonary Infections in Acquired Immunodeficiency Syndrome (AIDS)." American Journal of Clinical Pathology, January 1984, Vol. 81, No. 1: 1-5...... 3A3-Blu-7 Bonavida, Benjamin, Jonathan Katz, Michael Gottlieb. "Mechanism of Defective NK Cell Activity in Patients with Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related Complex." The Journal of Immunology, 15 August 1986, Vol. 137, No. 4: 1157-1163...... 4C2-Bon-1 Bouvet, E., J.B. Brunet, J. Chaperon et al. "Sarcome de Kaposi et Infections Opportunistes Chez des Sujets Jeunes sans Antecedent Susceptible d'Entrainer une Immunodepression." La Presse Medicale, 5 November 1983, Vol. 12, No. 39: 2431-2434......1B4-Bou-17 Boyko, William J., Martin T. Schechter, Kevin J.P. Craib et al. "The Vancouver Lymphadenopathy-AIDS Study: 5. Antecedent Behavioural, Clinical and Laboratory Findings in Patients with AIDS and HIV-Seropositive Controls." Canadian Medical Association Journal, 15 October 1986, Vol. 135: 88I- 887 cusses 1C3-Boy-2 Boyko, William J., Martin T. Schechter, Eric Jeffries et al. "The Vancouver Lymphadenopathy-AIDS Study: 3. Relation of HTLV-III Seropositivity, Immune Status and Lymphadenopathy." Canadian Medical Association Journal, 1 July 1985, Vol. 133: 28-32......3B-Boy->5 Boyko, William J., Martin T. Schechter, Peter Constance et al. "Limited Usefulness of Lymphocytopenia in Screening for AIDS in Hospital Patients." Canadian Medical Association Journal, 15 August 1985, Vol. 133: 293...... 3A3-Boy-2 Broaddus, Courtney, Michael D. Dake, Michael S. Stulbarg et al. "Bronchoalveolar Lavage and Transbronchial Biopsy for the Diagnosis of Pulmonary Infections in the Acquired Immunodeficiency Syndrome." Annals of Internal Medicine, June 1985, Vol. 102, No. 6: 747-752...... 3A3-Bro-3 Broder, Samuel, Jerry M. Collins, Phillip D. Markham et al. "Effects of Suramin on HTLV-III/LAV Infection Presenting as Kaposi's Sarcoma or AIDS-Related Complex: Clinical Pharmacology and Suppression of Virus Replication in Vivo." The Lancet, 21 September 1985, Vol. 2, No. 8456: 627-630...... 4C1-Bro-4 Bromwich, P.D., A.P. Walker, Sue H. Gregson et al. "Screening for Antibodies to HTLV- [II Amongst the Semen Donors of an AID Programme." British Journal of Obstetrics and Gynaecology, March 1986, Vol. 93: 279-281...... 2G-Bro-1 XV1l1 Brown, Lawrence S., Jr., Ruppert Evans, Debra Murphy et al. "Drug Use Patterns: Implications for the Acquired Immunodeficiency Syndrome." Journal of the National Medical Association, 1986, Vol. 78, No. 12: 1145-1151......1C2-Bro-2 Brun-Vezinet, R., C. Rouzioux, L. Montagnier et al. "Prevalence of Antibodies to Lymphadenopathy-Associated Retrovirus in African Patients with AIDS." Science, 26 October 1984, Vol. 226: 453-456......1B5-Bru-8 Brunet, J.B. "Acquired Immune Deficiency Syndrome in France." European Journal of Clinical Microbiology, February 1984, Vol. 3, No. 1: 66......1B4-Bru-8 Brunet, J.B. "The International Occurrence of the Acquired [Immunodeficiency Syndrome." Annals of Internal Medicine, November 1985, Vol. 103, No. 5: 670- 67Ueeuies 1B1-Bru-6 Budzko, Delia B., David L. Madden, William T. London et al. "Immunologic Alterations in Monkeys with Simian Acquired Immunodeficiency Syndrome (SAIDS)." Proceedings of the Society for Experimental Biology and Medicine, 1985, Vol. 179: 227-231......7A-Bud-5 Burger, Harold, Barbara Weiser, William S. Robinson et al. "Transmission of Lymphadenopathy-Associated Virus/Human T Lymphotropic Virus Type III in Sexual Partners: Seropositivity Does Not Predict Infectivity in All Cases." The American Journal of Medicine, July 1986, Vol. 81: 5-10......2A-Bur-2 Carlson, James R., Martin L. Bryant, Steven H. Hinrichs et al. "AIDS Serology Testing in Low- and High-Risk Groups." Journal of the American Medical Association, 21 June 1985, Vol. 253, No. 23: 3405-3408......5B1-Car-10 Carne, C.A., S. Sutherland, R.B. Ferns et al. "Rising Prevalence of Human T Lymphotropic Virus Type III (HTLV-II) in Homosexual Men in London." The Lancet, | June 1985, Vol. 1, No. 8440: 1261-1262..... JC3-Car-11 Cavaille-Coll, M., A. Messiah, D. Klatzmann et al. 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Journal of Community Health, Winter 1986, Vol. 11, No. 42 233-2830 0eure 5A2-Sie-4 Silvestre, Anthony, David W. Lyter, Charles R. Rinaldo et al. "Marketing Strategies for Recruiting Gay Men into AIDS Research and Education Projects." Journal of Community Health, Winter 1986, Vol. 11, No. 4: 222-232...... 5A 1-Sil-1 Sirianni, M.C., P. Rossi, M. Moroni et al. "Demonstration of Antibodies to Human T- Lymphotropic Retrovirus Type III in Lymphadenopathy Syndrome Patients and in Individuals at Risk for Acquired Immune Deficiency Syndrome (AIDS) in Italy." American Journal of Epidemiology, 1986, Vol. 123, No. 2: 308-315...... 1B4-Sir-2 x1iii Snider, William D., David M. Simpson, Surl Nielsen et al. "Neurological Complications of Acquired Immune Deficiency Syndrome: Analysis of 50 Patients." Annals of Neurology, October 1983, Vol. 14, No. 4: 403-418...... 3D-Sni-11 Spire, B., L. Montagnier, F. Barre-Sinoussi et al. "Inactivation of Lymphadenopathy Associated Virus by Chemical Disinfectants." The Lancet, 20 October 1984, Vol. 2, No. 8408: 899-901...... 5C-S5pi-3 Stahl-Bayliss, Celine M., Concetta M. Kalman, Oscar L. Laskin. "Pentamidine-Induced Hypoglycemia in Patients with the Acquired Immune Deficiency Syndrome." Clinical Pharmacological Therapy, March 1986, Vol. 39, No. 3: 271-275...... 4B- Sta-3 Stall, Ron, Leon McKusick, James Wiley et al. "Alcohol and Drug Use During Sexual Activity and Compliance with Safe Sex Guidelines for AIDS: The AIDS Behavioral Research Project." Health Education Quarterly, Winter 1986, Vol. 13; No. 42 359-37 Levees 1C2-Sta-1 Stevens, Cladd E., Patricia E. Taylor, Edith A. Zang et al. "Human T-Cell Lymphotropic Virus Type III Infection in a Cohort of Homosexual Men in New York City." Journal of the American Medical Association, 25 April 1986, Vol. 255, No. 16: 2167-2172.cuu0. 3C-Ste->5 Steinbrook, Robert, Bernard Lo, Jeffrey Moulton et al. "Preferences of Homosexual Men with AIDS for Life-Sustaining Treatment." The New England Journal of Medicine, 13 February 1986, Vol. 314, No. 7: 457-460...... 6A-Ste-1 Stewart, G.J., A.L. Cunningham, G.L. Driscoll et al. "Transmission of Human T-Cell Lymphotropic Virus Type III (HTLV-III) by Artificial Insemination by Donor." The Lancet, 14 September 1985, Vol. 2, No. 8455: 581-584...... 2G-Ste-2 Sumaya, Ciro Valent, Richard Neal Boswell, Yasmin Ench et al. "Enhanced Serological and Virological Findings of Epstein-Barr Virus in Patients with AIDS and AIDS- Related Complex." The Journal of Infectious Diseases, November 1986, Vol. 154, No. 5: 864-870...... 1C3-Sum-1 Sydney AIDS Study Group. "The Sydney AIDS Project.” The Medical Journal of Australia, 27 October 1984, Vol. 141: 569-573...... 1B3-Syd-1 Tavitian, Avedis, Jean-Pierre Raufman, Linda E. Rosenthal. "Oral Candidiasis as a Marker for Esophageal Candidiasis in the Acquired Immunodeficiency Syndrome." Annals of Internal Medicine, January 1986, Vol. 104, No. l: 54- 3 3A4-Tav-3 Taylor, Jeremy, Rahmat Afrasiabi, John L. Fahey et al. "Prognostically Significant Classification of Immune Changes in AIDS with Kaposi's Sarcoma." Blood, March 1986, Vol. 67, No. 3: 666-671......3C-Tay-8 Taylor, Jeremy M.G., Kendra Schwartz, Roger Detels. "The Time from Infection with Human Immunodeficiency Virus (HIV) to the Onset of AIDS." The Journal of Infectious Diseases, October 1986, Vol. 154, No. 4: 694-697...... 3C-Tay-1 liv Tedder, R.S., D.C. Shanson, D.J. Jeffries et al. "Low Prevalence in the UK of HTLV-I and HTLV-II Infection in Subjects with AIDS, with Extended Lymphadenopathy, and at Risk of AIDS." The Lancet, 21 July 1984, Vol. 2, No. 8395: 125-128..... . 1C3-Ted-12 Tenner-Racz, Klara, P. Racz, Margarita Bofill et al. "HTLV-III/LAV Viral Antigens in Lymph Nodes of Homosexual Men with Persistent Generalized Lymphadeno- pathy and AIDS." American Journal of Pathology, April 1986, Vol. 123, No. I: 9-1 3uerens 3B-Ten-1 Thomas, Pauline A., Harold W. Jaffe, Thomas J. Spira et al. "Unexplained Immuno- deficiency in Children: A Surveillance Report." Journal of the American Medical Association, 3 August 1984, Vol. 252, No. 5: 639-644...... LA4-Tho-7 Tsai, Che-Chung, Thomas F.C.S. Warner, Hideo Uno et al. "Subcutaneous Fibromatosis Associated with an Acquired Immune Deficiency Syndrome in Pig-Tailed Macaques." American Journal of Pathology, July 1985, Vol. 120, No. 1: 30- 37 sem 7A-Tsa-3 Tsang, Peter H., Khanitha Tangnavarad, Stephen Solomon et al. "Modulation of T- and B- Lymphocyte Functions by I[soprinosine in Homosexual Subjects with Prodromata and in Patients with Acquired Immune Deficiency Syndrome (AIDS)." Journal of Clinical Immunology, 1984, Vol. 4, No. 6: 469-478...... 4Cl1-Tsa-9 Ultmann, Monica H., Anita L. Belman, Holly A. Ruff et al. "Developmental Abnormali- ties in Infants and Children with Acquired Immune Deficiency Syndrome (AIDS) and AIDS-Related Complex." Developmental Medicine and Child Neurology, 1985, Vol. 27: 563-571...... LA4-Ult-6 Valone, Frank H., Donald G. Payan, Donald I. Abrams et al. "Indomethacin Enhances the Proliferation of Mitogen-Stimulated T Lymphocytes of Homosexual Males with Persistent Generalized Lymphadenopathy." Journal of Clinical Immunology, 1984, Vol. 4, No. 5: 383-387...... 4C2-Val-13 Van de Perre, Philippe, Philippe LePage, Philippe Kestelyn et al. "Acquired Immunodefi- ciency Syndrome in Rwanda." The Lancet, 14 July 1984, Vol. 2, No. 8394: 62- 64...... 1B5-Van-10 Van de Perre, Philippe, Michel Carael, Marjorie Robert-Guroff et al. "Female Prosti- tutes: A Risk Group for Infection with Human T-Cell Lymphotropic Virus Type [II." The Lancet, 7 September 1985, Vol. 2, No. 8454: 524-526...... lA6-Van-5 Vandenbroucke-Grauls, C.M., J. Verhoef. "Acquired Immune Deficiency Syndrome in the Netherlands." European Journal of Clinical Microbiology, February 1984, Vol. 3, No. 1% 62.000es IB4-Van-15 Vaziri, N.D., A. Barbari, K. Licorish et al. "Spectrum of Renal Abnormalities in Acquired Immune-Deficiency Syndrome." Journal of the National Medical Asso- ciation, 1985, Vol. 77, No. 5: 369-375...... 3A4-Vaz-8 Verani, Paola, Guglielmo Mariani, Pier M. Mannucci et al. "Prevalence of HTLV-III/LAV Antibodies in [Italian Asymptomatic Hemophiliacs Given Commercial Concentrates of Factors VIII and IX." Journal of Medical Virology, 1986, Vol. 19: 143-149,.000 2C-Ver-7 x1v Volberding, Paul A., Donald I. Abrams, Marcus Conant et al. "Vinblastine Therapy for Kaposi's Sarcoma in the Acquired Immunodeficiency Syndrome." Annals of Internal Medicine, September 1985, Vol. 103, No. 3: 335-338......4B-Vol-4 Volberding, Paul, Marcus A. Conant, Raphael B. Stricker et al. "Chemotherapy in Advanced Kaposi's Sarcoma: Implications for Current Cases in Homosexual Men." The American Journal of Medicine, April 1983, Vol. 74, No. 4: 652- 636..00v+ 3A1-Vol-9 Volberding, Paul, Ruben Valero, John Rothman et al. "Alpha Interferon Therapy of Kaposi's Sarcoma in AIDS." Annals of New York Academy of Sciences, 1984, Vol. 437: 439-44e...... 4C2-Vol-14 Vrang, Lotta, Bo Oberg. "PP, Analogs as Inhibitors of Human T-Lymphotropic Virus Type [II Reverse Transcriptase." Antimicrobial Agents and Chemotherapy, May 1986, Vol. 29, No. 3: 367-872:uce0« 4Cl-Vra-1 Weber, J.N., L.A. Rogers, K. Scott et al. "Three-Year Prospective Study of HTLV- I[II/LAV Infection in Homosexual Men." The Lancet, 24 May 1986, Vol. 1, No. 8491: 1179-1182...... 3C-Web-3 Weiss, Stanley H., James J. Goedert, M.G. Sarngadharan et al. "Screening Test for HTLV-II (AIDS Agent) Antibodies: Specificity, Sensitivity, and Applications." Journal of the American Medical Association, Il January 1985, Vol. 253, No. 2: 221-225...... S5B-Wei-12 Weiss, Stanley H., W. Carl Saxinger, David Rechtman et al. "HTLV-II Infection Among Health Care Workers: Association with Needle-Stick Injuries." Journal of the American Medical Association, 18 October 1985, Vol. 254, No. 15: 2089- 2093.0000 2E-Wei-4 Wendler, I., J. Schneider, B. Gras et al. "Seroepidemiology of Human Immunodeficiency Virus in Africa." British Medical Journal, 27 September 1986, Vol. 293: 782- 735.0000 1B5-Wen-3 Wharton, J. Marcus, Diana Lewis Coleman, Constance B. Wofsy et al. "Trimethoprim- Sulfamethoxazole or Pentamidine for Pneumocystis carinii Pneumonia in the Acquired Immunodeficiency Syndrome: A Prospective Randomized Trial." Annals of Internal Medicine, July 1986, Vol. 105, No. 1: 37-44...... 4B-Wha-2 Wheat, L. Joseph, Thomas G. Slama, Michael L. Zeckel. "Histoplasmosis in the Acquired Immune Deficiency Syndrome." The American Journal of Medicine, February 1935, Vol. 73: 203-210..005: 3A4-Whe-6 Whelan, Margaret Anne, Irvin I. Kricheff, Michael Handler et al. "Acquired Immunodeficiency Syndrome: Cerebral Computed Tomographic Manifesta- tions." Radiology, 1983, Vol. 149: 477-484...... 3D-Whe-12 Whiteside, Mark E., Jamie S. Barkin, Richard G. May et al. "Enteric Coccidiosis Among Patients with the Acquired Immunodeficiency Syndrome." The American Journal of Tropical Medicine and Hygiene, 1984, Vol. 33, No. 6: 1065- 10720000 3A2-Whi-4 x1lvi Williams, Linda Stewart. "AIDS Risk Reduction: A Community Health Education Intervention for Minority High Risk Group Members." Health Education Quarterly, Winter 1986, Vol. 13, No. 4: 407-421......5A1-Wil-2 Winter, Stephen M., Edward M. Bernard, Jonathan W.M. Gold et al. "Humoral Response to Disseminated Infection bv Mycobacterium avium-Mycobacterium intracellu- lare in Acquired Immunodeficiency Syndrome and Hairy Cell Leukemia." The Journal of Infectious Diseases, March 1985, Vol. 151, No. 3: 523-527...... 3E- Win-5 Wollschlager, Christine M., Faroque A. Khan, Rajinder K. Chitkara et al. "Pulmonary Manifestations of the Acquired Immunodeficiency Syndrome (AIDS)." Chest, February 1984, Vol. 85, No. 2: 197-202...... 3A3-Wol-6 Wong, Brian, Jonathan W.M. Gold, Arthur E. Brown et al. "Central-Nervous-System Toxoplasmosis in Homosexual Men and Parenteral Drug Abusers." Annals of Internal Medicine, January 1984, Vol. 100, No. l: 36-42...... 3D-Won-10 Wood, Chester C., Alan E. Williams, James G. McNamara et al. "Antibody against Human Immunodeficiency Virus in Commercial Intravenous Gammaglobulin Preparations." Annals of Internal Medicine, October 1986, Vol. 105, No. 4: 536- 538.0000.2C-Wo00-2 Wormser, Gary P., Lauren B. Krupp, John P. Hanrahan et al. "Acquired Immunodeficien- cy Syndrome in Male Prisoners: New Insights into an Emerging Syndrome." Annals of Internal Medicine, March 1983, Vol. 98, No. 3: 297-303...... 1A7-Wor-7 Ziegler, John L., Jay A. Beckstead, Paul A. Volberding et al. "Non-Hodgkin's Lymphoma in 90 Homosexual Men: Relation to Generalized Lymphadenopathy in the Acquired Immunodeficiency Syndrome." The New England Journal of Medicine, 30 August 1984, Vol. 311, No. 9: 565-570...... 3A4-Zie-10 Ziegler, John B., Richard O. Johnson, David A. Cooper et al. "Postnatal Transmission of AIDS-Associated Retrovirus From Mother to Infant." The Lancet, 20 April 1985, Vol. 1, No. 8434: 896-893...... 2G-Zie-3 x1lvii IAT: Abstracts in Section Collier Fauci Gerstoft Guinan Jaffe Melbye 1A1-Col-1 1A1-Fau-6 1A1-Ger-7 1A1-Gui=5 1A1-Jaf-2, 1A1-Jaf-3 1A1-Me | -4 x1ix Other Related Abstracts Abrams Auerbach Biberfeld Boyko Brunet Carlson Carne Cavaille-Col | Centers for Disease Control Coates Cooper Coutinho Daul Detels Emmons Fishbein Frazer Gazzard Gilmore Glauser Goedert Gold Greenspan Groopman Hardy Institute of Cancer Research Jaffe Jeffries Kalish Kalyanaraman Kekow Khadem Lozada Lozada-Nur Manger Martin Mayer McKusick Melbye Mittelman Mortimer Moss Patow Rank i Rogers Ross Schechter Siegel 3B-Abr-12 2A-Aue-6 2C-Bib-10 3B-Boy-5 1B1-Bru-6 5B1-Car-10 1C3-Car-11 3B-Cav-17 5A2-Cen-6 3C-Coa-4 3B8-Coo-7 3C-Cou-9 1C3-Dau-7 1C3-Det-,14 2A-Det-7 S5A2-Emm-1 3B-Fis-4 1B3-Fra-2 2A-Gaz-5 3B-Gil-18 1B4-Gla-11 1B1-Goe-5, 1B1-Goe-9,1C1-Goe-2, 2A-Goe-4 3B-Gol-9 3A4-Gre-9 3B-Gro-8 1B1-Har-8 1B4-1ns-16 1C1-Jaf-3,3C-Jaf-12 3C-Jef-11 3B-Kal-15 1B1-Kal-10 3E-Kek-8 3A4-Kha-14 3A4-Loz-16 3B-Loz-13 3B-Man-16 5A2-Mar-3 1C1-May-1,5B2-May-2 5A2-McK-7 3C-Mel-7 3A1-Mit-2 1B4-Mor-4 1B1-Mos-7 3A1-Pat-7 1C3-Ran-9 1C1-Rog-4 5B82-Ros-6 3B8-Sch-6 5A2-Sie-4 Abstracts in Section 1A1: cont. IA2: Crovari Des Jarlais Friedland Lazzarin IA3: Allain Ball Bloom Centers for Disease Control Daly Daniel deShazo Evatt Green Jason Johnson Jones Kitchen Kreiss Lederman Ragni 1A2-Cro-3 1A2-Des-1 1A2-Fri-2 1A2-Laz-4 1A3-A1 1-15 1A3-Bal-9 1A3-Blo-14 1A3-Cen-1 1A3-Dal-12 1A3-Dan-5 1A3-deS-17 1A3-Eva-11 1A3-Gre-16 1A3-Jas-2,1A3-Jas-8 1A3-Joh-13 1A3-Jon-7 1A3-Kit-6 1A3-Kre-3 1A3-Led-10 1A3-Rag-4 Other Related Abstracts Silvestre Sirianni Stall Sydney AIDS Study Group Taylor Volberding Weber Brown Brunet Centers for Disease Control Collier Fauci Friedman Goedert Guinan Hardy Institute of Cancer Research Koppe | Maayan Mortimer Robertson Sirianni Williams Allain Berthier Biberfeld Carlson Daul Erfle Evatt Eyster Fauci Fuchs Giudizi Gjerset Goedert Hardy Hil fenhaus Institute of Cancer Research Jason Kitchen Kloster Kreiss Lawrence Me lbye Mortimer Rouzioux SA1-Sil-1 1B4-Sir-2 1C2-Sta-1 183-Syd-1 3C-Tay-8 3A1-Vol-9 3C-Web-3 1C2-Bro-2 1B1-Bru-6 1A7-Cen-4 1A1-Co!-1 1A1-Fau-6 SA2-Fri-2 1B1-Goe-5 1A1-Gui-5 1B1-Har-8 1B4-1ns-16 3D-Kop-7 1A5-Maa-2 1B4-Mor-4 2B-Rob-1 1B4-Sir-2 SA1-Wil-2 2C-Al1-9 2F-Ber-1 2C-Bib-10 5B1-Car-10 1C3-Dau-7 2C-Erf-18 1B1-Eva-12 3B-Eys-19,3C-Eys-13 1A1-Fau-6 3A3-Fuc-4 2C-Giu-6 2C-Gje-11 1B1-Goe-5,2C-Goe-17 1B1-Har-8 5B3-Hil-2 1B4-Ins-16 2A-Jas-3,2C-Jas-26 2C-Kit-21 2C-Kio-15 1A6-Kre-6 2F-Law-4 2C-Me | -20 1B4-Mor-4 2C-Rou-16 1A3: cont. 1A4: IAS: 1A6: |A7: Abstracts in Section Ammann Lapointe Lauzon Mann Pahwa Rosner Rubinstein Thomas Ultmann Centers for Disease Control Maayan Pitchenik Centers for Disease Control Clumeck Harris Kreiss Redfield Van de Perre Centers for Disease Control Desmyter Hanrahan Kuritsky Wormser 1A4-Amm-4 1A4-Lap-8 1A4-Lau-2 1A4-Man-1 1A4-Pah-3 1A4-Ros-5 1A4-Rub-9 1A4-Tho-7 1A4-UIt-6 1A5-Cen-1 1A5-Maa-2 1A5-Pit-3,1A5-Pit-4 1A6-Cen-4 1A6-Clu-2 1A6-Har-8 1A6-Kre-1,1A6-Kre-6 1A6-Red-3,1A6-Red-7 1A6-Van-5 1A7-Cen-2,1A7-Cen-3,1A-Cen-4 1A7-Des-1 1A7-Han-6 1A7-Kur-5 1A7-Wor-7 11 Other Related Abstracts Sirianni Verani Blanche Centers for Disease Control Cowan Hardy Haverkos Joshi Mann Scott Sharer Centers for Disease Control Fauci Glauser Guinan Hardy Institute of Cancer Research Williams Barin Brunet Burger Centers for Disease Control Chamber land Collier Crovari deShazo Fauci Glauser Guinan Hardy Institute of Cancer Research Piot Pitchenik Van de Perre Carlson Centers for Disease Control Clumeck Contreras Crovari Dienstag Fang Henderson Jaffe Kalyanaraman 1B4-Sir-2 2C-Ver-7 3A2-Bla-1 2D-Cen-1 2D-Cow-4 1B1-Har-8 4B-Hav-9 3C-Jos-19 1B5-Man-2 2D-Sco-3,2D-Sco-5 3D-Sha-3 1B1-Cen-1,3A4-Cen-1 1A1-Fau-6 1B4-Gla-11 1A1-Gui-5 1B1-Har-8 1B4-1Ins-16 S5A1-Wil-2 78-Bar-2 1B1-Bru-6 2A-Bur-2 2A-Cen-1 2C-Cha-22 1A1-Col -1 1A2-Cro-3 1A3-deS-17 1A1-Fau-6 1B4-Gla-11 1A1-Gui-5 1B1-Har-8 1B4-1ns-16 1B5-Pio-9 1A5-Pit-4 1B5-Van-10 5B1-Car-10 1A6-Cen-4 1A6-Clu-2 582-Con-7 1A2-Cro-3 2C-Die-12 5B1-Fan-4 2E-Hen-2 2C-Jaf-23 1B1-Kal-10 1A7: cont. 1B1: 1B2: 1B3: 1B4: Abstracts in Section Brunet Centers for Disease Control Elmslie Evatt Goedert Hardy Jaffe Kalyanaraman Kristal Morgan Moss Selik Climent Pape Rodriguez Frazer Sydney AIDS Study Group Aiuti Bouvet Brunet Centers for Disease Control Clauvel Clumeck Gerstoft Glauser Heh Imann Hunsmann Institute of Cancer Research L'age-Stehr McEvoy Mortimer Repo Sirianni 1B1-Bru-6 1B1-Cen-1 1B1-EIm-2 1B1-Eva-12 1B1-Goe-5,1B1-Goe-9 1B1-Har-8 1B1-Jaf-13 1B1-Kal-10 1B1-Kri-4 1B1-Mor-3 1B1-Mos-7 1B1-Sel-11 1B2-Cli-2 1B2-Pap-3 1B2-Rod-1 1B3-Fra-2 183-Syd-1 1B4-Aiu-3 1B4-Bou-17 1B4-Bru-8 1B4-Cen-1 1B4-Cla-9 1B4-Clu-10 1B4-Ger-5 1B4-Gla-11 1B4-Heh-6 1B4-Hun-7 1B4-1Ins-16 1B4-Lag-12 1B4-McE-13 1B4-Mor-4 1B4-Rep-14 1B4-Sir-2 Other Related Abstracts Kuhn Mortimer Pindyck Rhame Sacks Sayers Weiss Boyko Centers for Disease Control Chamber | and Coleman Evatt Fauci Goedert Groopman Guinan Jaffe Jason Jeffries Lauzon Peterman Schechter Volberding Brunet de-The Pitchenik Cooper Ross Stewart Allain Biberfeld Brunet Carne Cavaille-Col | Coutinho Crovari Daniel Desmyter Erfle Gazzard Gerstoft Giudizi Goldman Green Jones Kekow Kitchen 5B1-Kuh-6 5B81-Mor-9 582-Pin-9 2E-Rha-8 2C-Sac-19 5B2-Say-5 2E-Wei-4 3A3-Boy-2 1A3-Cen-1,1A5-Cen-1,1A7-Cen-4, 2D-Cen-1 2C-Cha-22 3C-Col-6 1A3-Eva-11 1A1-Fau-6 2A-Goe-4 3B-Gro-8 1A1-Gui=-5 1A1-Jaf-2 2A-Jas-3 3C-Jef-11 1A4-Lau-2 2C-Pet-8 3B-Sch-6 3A1-Vol-9 1B1-Bru-6 1B5-deT-5 1A5-Pit-4 3B-Coo-7,3C-Coo-17 5B2-Ros-6 2G-Ste-2 1A3-A11-15,2C-A11-9 2C-Bib-10 1B1-Bru-6 1C3-Car-11 3B-Cav-17 3C-Cou-9 1A2-Cro-3 1A3-Dan-5 1A7-Des-1 2C-Erf-18 2A-Gaz-5 1A1-Ger-7 2C-Giu-6 2C-Gol-3 1A3-Gre-16 1A3-Jon-7 3E-Kek-8 1A3-Kit-6 Abstracts in Section IB4: Vandenbroucke- cont. Grauls IBS: Biggar Brun-Vezinet Clumeck de-The Mann Piot Quinn Saxinger Van de Perre Wendler IB6: Hattori IC1: Goedert Jaffe Mayer Rogers IC2: Brown Haverkos Stall C3: Birx Boyko Carne Centers for Disease Control Daul Detels Greenberg Halbert Perrillo Quinnan Rank i Rinaldo Schechter 1B4-Van-15 185-Big-6 1B5-Bru-8 1B5-Clu-11 1B5-deT-5 1B5-Man-2, I1B5-Man-4 1B5-Pio-9 1B5-Qui-1 1B5-Sax-7 1B5-Van-10 1B5-Wen-3 1B6-Hat-1 1C1-Goe-2 1C1-Jaf-3 1C1-May-1 1C1-Rog-4 1C2-Bro-2 1C2-Hav-3 1C2-Sta-1 1C3-Bir-6 1C3-Boy-2 1C3-Car-11 1C3-Cen-15 1C3-Dau-7 1C3-Det-14 1C3-Gre-5 1C3-Hal-8 1C3-Per-4 1C3-Qui-13 1C3-Ran-9 1C3-Rin-3 1C3-Sch-10 1111 Other Related Abstracts Kuhn Lazzarin Lindhardt Manger Me lbye Mortimer Rank i Robertson Rouzioux Schupbach Tedder Verani Weber Barin Bayley Brunet Clumeck Downing Kank i Kreiss Mann Otu Van de Perre Biggar Cooper Goedert Groopman Jeffries Mel bye Volberding Lozada Me lbye Schechter Anderson Collier de-The Gascon Guinan Hattori Jeffries Lozada Mathur-Wagh Melbye Pitchenik Redfield Rodman Rogers 5B1-Kuh-6 1A2-Laz-4 582-Lin-3 3B-Man-16 1A1-Mel-4,2C-Me|-20,3C-Me|-7 5B81-Mor-9 1C3-Ran-9 2B-Rob-1 2C-Rou-16 5B1-Sch-11 1C3-Ted-12 2C-Ver-17 3C-Web-3 7B-Bar-2 3A1-Bay-5,3A1-Bay-6 1B1-Bru-6 1A6-Clu-2,1B4-Clu-10 3A1-Dow-8 7B-Kan-1 1A6-Kre-1 1A4-Man-1,2E-Man-1,2F-Man-2, 3C-Man-2 3A1-0tu-1 1A6-Van-5 1B5-Big-6 3C-Coo-7 1B1-Goe-9,2A-Goe-4 3B-Gro-8 3C-Jef-11 1A1-Mel-4 3A1-Vol-9 3A4-Loz-16 1A1-Mel-4 1C3-Sch-10 2C-And-1 1A1-Col -1 1B5~-deT-5 2C-Gas-24 1A1-Gui-5 1B6-Hat-1 3C-Jef-11 3A4-Loz-16 3B-Mat-14 1A1-Mel-14 1A5-Pit-3,1A5-Pit-4 1A6-Red-3 3E-Rod-1 1C1-Rog-4 1C3: Abstracts in Section Sumaya cont. Tedder 1C4: 1A. IIB. Auerbach Burger Centers for Disease Control Detels Gazzard Goedert Jason Robertson 1C3-Sum-1 1C3-Ted-12 2A-Aue-6 2A-Bur-2 2A-Cen-1 2A-Det-7 2A-Gaz-5 2A-Goe-4 2A-Jas-3 2B-Rob-1 liv Other Related Abstracts Saxinger Sirianni Vandenbroucke- Grauls Weber Brunet Burger Gerstoft Glauser Guinan Institute of Cancer Research McEvoy Vandenbroucke- Grauls Anderson Boyko Centers for Disease Control Chamber land Clumeck Cooper Crovari Detels Gerstoft Goedert Groopman Harris Jaffe Jeffries Kaplan Kreiss Mann McEvoy McKusick Piot Pitchenik Redfield Rodman Rogers Schechter Stevens Stewart Van de Perre Vandenbroucke- Grauls Weiss Brown Crovari Des Jarlais Friedland 1B5-Sax-7 1B4-Sir-2 1B4-Van-15 3C-Web-3 1B4-Bru-8 2A-Bur-2 1B4-Ger-5 1B4-Gla-11 1A1-Gui=5 1B4-Ins-16 1B4-McE-13 1B4-Van-15 2C-And-1 1C3-Boy-2 1A6-Cen-4,2D0-Cen-1,5A2-Cen-6 2C-Cha-22 1A6-Clu-2,1B4-Clu-10 3C-Coo-17 1A2-Cro-3 1C3-Det-14 1B4-Ger-5 1B1-Goe-9,1C1-Goe-2 3B8-Gro-8 1A6-Har-8 1A1-Jaf-2,1C1-Jaf-3 3C-Jef-11 2D-Kap-2 1A6-Kre-6 2F-Man-2 1B4-McE-13 5A2-McK-7 1B5-Pio-9 1AS-Pit-4 1A6-Red-3,1A6-Red-7 3E-Rod-1 1C1-Rog-4 1C3-Sch-10,3B-Sch-6 3C-Ste-5 2G-Ste-2 1A6-Van-5 1B4-Van-15 2E-Wei-4 1C2-Bro-2 1A2-Cro-3 1A2-Des-1 1A2-Fri=-2 118. cont. Hic. 11D. IE. VIF, 1G. Abstracts in Section Allain Anderson Biberfeld Centers for Disease Control Chamber | and Curran Dienstag Erfle Feorino Gascon Giudizi Gjerset Goedert Goldman Jaffe Jason Kitchen Kloster Melbye Peterman Rouzioux Sacks Verani Wood Centers for Disease Control Cowan Kaplan Scott Centers for Disease Control Henderson Hirsch Mann McCray Rhame Weiss Berthier Friedland Lawrence Mann Bromwich Stewart Ziegler 2C-Al1-9 2C-And-1 2C-Bib-10 2C-Cen-5 2C-Cha-22 2C~Cur-25 2C-Die-12 2C-Erf-18 2C-Feo-14 2C-Gas-24 2C-Giu-6 2C-Gje-11 2C-Goe-17 2C-Gol-3 2C-Jaf-13,2C-Jaf-23 2C-Jas-26 2C-Kit-21 2C-Klo-15 2C-Me 1-20 2C-Pet-4,2C-Pet-8 2C-Rou-16 2C-Sac-19 2C-Ver-7 2C-Woo-2 2D-Cen-1 2D-Cow-4 2D-Kap-2 2D-Sco-3,2D-Sco-5 2E-Cen-5,2E-Cen-7 2E-Hen-2 2E-Hir-6 2E-Man-1 2E-McC-3 2E-Rha-8 2E-Wei-4 2F-Ber-1 2F-Fri-3 2F-Law-4 2F-Man-2 2G-Bro-1 2G-Ste-2 2G-Zie-3 1v Other Related Abstracts Hanrahan Wormser Alter Bal | Bloom Centers for Disease Control Daly Daniel deShazo Desmyter Evatt Green Hil fenhaus Jason Johnson Jones Kaplan Kitchen Kreiss Lederman Mann McDougal Ragni Friedland Lapointe Mann Pahwa Rubinstein Stewart Centers for Disease Control Goldman Lawrence Jason Lapointe Pahwa Redfield Archibald Centers for Disease Control 1A7-Han-6 1A7-Wor-7 TA-AIt-7 1A3-Bal-9 1A3-Blo-14 2D-Cen-1 1A3-Dal-12 1A3-Dan-5 1A3-deS-17 1A7-Des-1 1A3-Eva-11 1A3-Gre-16 583-Hi | -2 1A3-Jas-2,1A3-Jas-8 1A3-Joh-13 1A3-Jon-7 2D-Kap-2 1A3-Kit-6 1A3-Kre-3 1A3-Led-10 1A4-Man-1 582-McD-8 1A3-Rag-4 2F-Fri-3 1A4-Lap-8 1A4-Man-1 1A4-Pah-3 1A4-Rub-9 2G-Ste-2 2C-Cen-5 2C-Gol-3 2F-Law-4 2A-Jas-3 1A4-Lap-8 1A4-Pah-3 1A6-Red-7 3F-Arc-1 1B1-Cen-1,2D-Cen-1 1B. cont. Vic. 40 VIE. IF. 1G. Abstracts in Section Allain Anderson Biberfeld Centers for Disease Control Chamber | and Curran Dienstag Erfle Feorino Gascon Giudizi Gjerset Goedert Goldman Jaffe Jason Kitchen Kloster Me lbye Peterman Rouzioux Sacks Verani Wood Centers for Disease Control Cowan Kaplan Scot’ Centers for Disease Control Henderson Hirsch Mann McCray Rhame Weiss Berthier Friedland Lawrence Mann Bromwich Stewart Ziegler 2C-Al1-9 2C-And-1 2C-Bib-10 2C-Cen-5 2C-Cha-22 2C-Cur-25 2C-Die-12 2C-Erf-13 2C-Feo-14 2C-Gas-24 2C-Giu-6 2C-Gje-11 2C-Goe-17 2C-Gol-3 2C-Jat-13,2C~-Jat~23 2C-Jas-26 2C-Kit-21 2C-Klo-15 2C-Mel-20 2C-Pet-4,2C-Pet-8 2C-Rou-16 2C-Sac-19 2C-Ver-7 2C-Woo-2 2D-Cen-1 2D-Cow-4 2D-Kap-2 2D-Sco-3,2D-Sco-5 2E-Cen-5,2E-Cen-7 2E-Hen-2 2E-Hir-6 2E-Man-1 2E-McC-3 2E-Rha-8 2E-Wei-4 2F-Ber-1 2F-Fri-3 2F-Law-4 2F-Man-2 2G-Bro-1 2G-Ste-2 2G-2ie-3 1vi Other Related Abstracts Hanrahan Wormser Alter Bal | Bloom Centers for Disease Control Daly Daniel deShazo Desmyter Evatt Green Hil fenhaus Jason Johnson Jones Kaplan Kitchen Kreiss Lederman Mann McDougal Ragni Friedland Lapointe Mann Pahwa Rubinstein Stewart Centers for Disease Control Goldman Lawrence Jason Lapointe Pahwa Redfield Archibald Centers for Disease Control 1A7-Han-6 1A7-Wor-7 TA-Al+=7 1A3-Bal-9 1A3-Blo-14 2D-Cen-1 1A3-Dal-12 1A3-Dan-5 1A3-deS-17 1A7-Des-1 1A3-Eva-11 1A3-Gre-16 5B3~Hi | -2 1A3~-Jas-2,1A3-Jas-8 1A3-Joh-13 1A3-Jon-7 2D-Kap-2 1A3-Kit-6 1A3-Kre-3 1A3-Led-10 1A4-Man-1 582-McD-8 1A3-Rag-4 2F=Fri-3 1A4-Lap-8 1A4-Man-1 1A4-Pah-3 1A4-Rub-9 2G-Ste~2 2C-Cen-5 2C-Gol-3 2F-Law-4 2A-Jas-3 1A4-Lap-8 1A4-Pah-3 1A6-Red-7 3F-Arc-1 1B1-Cen-1,2D-Cen-1 1G. cont. ETAL: I11A2: Abstracts Bayley Downing Mittelman Moskowitz Ognibene Otu Patow Volberding Blanche Kovacs Lerner Macher Whiteside in Section 3A1-Bay-5,3A1-Bay-6 3A1-Dow-8 3A1-Mit=-2 3A1-Mos-3 3A1-0Ogn-4 3A1-0tu-1 3A1-Pat-7 3A1-Vol-9 3A2-Bla-1 3A2-Kov-2 3A2-Ler-3 3A2-Mac-5 3A2-Whi-4 lvii Other Related Abstracts Clumeck Desmyter Fultz Mann Salahuddin Auerbach Climent Cooper Frederick Gelmann Glauser Groopman Haverkos Institute of Cancer Research Lane Lozada Lozada-Nur Mintzer Mittelman Moon Moss Navia Preble Van de Perre Volberding Blumenfeld Broaddus Centers for Disease Control Cl iment Coleman Glauser Haverkos Institute of Cancer Research Lane Lapointe Lauzon Leoung Maayan Moss Navia Nielsen Pape Rosner Thomas Wharton Wol lschlager 1B4-Clu-10 1A7-Des-1 TA-Ful-1 1A4-Man-1,2E-Man-1 5B2-Sal-10 2A-Aue-6 1B2-Cli-2 4B-Coo-6 4C2-Fre-4 4C2-Gel-6 1B4-Gla-11 4C1-Gro~-7 1C2-Hav-3 1B4-1ns-16 3C-Lan-14 3A4-Loz-16 3B-Loz-13 4B-Min-5 4C2-Mit-15 3A3-Moo-5 3C-Mos-16 3D-Nav-2 4C2-Pre-3 1B5-Van-10 4B-Vol-4, 4C2-Vol-14 3A3-Blu-7 3A3-Bro-3 4B-Cen-8,4B-Cen-10 1B2-Cti-2 3A3-Col-10 1B4-Gla-11 4B-Hav-9 1B4-1ns-16 3C-Lan-14 1A4-Lap-8 1A4-Lau-2 4B-Leo-! 1A5-Maa-2 3C-Mos-16 3D-Nav-2,3D-Nav-4 3D-Nie-8 1B2-Pap-3 1A4-Ros-5 1A4-Tho-7 4B-Wha-2 3A3-Wol-6 I11A3: [1 1A4: 1118: ivic: Abstracts in Section Bigby Blumenfeld Boyko Broaddus Coleman Fuchs Kern Moon Wol Ischlager Abrams Centers for Disease Control Freeman Gardenswartz Greenspan Khadem Lozada Marcusen Niedt Pitchenik Rao Rosenberg Tavitian Vaziri Wheat Ziegler Abrams Boyko Cavaille-Col | Cooper Eyster Fishbein Gilmore Gold Groopman Kalish Klein Laurence Lozada-Nur Manger Mathur-Wagh Murray Sandor Schechter Tenner-Racz Biberfeld Coates Coleman Cooper Coutinho 3A3-Big-1 3A3-Blu-7 3A3-Boy-2 3A3-Bro-3 3A3-Col-10 3A3-Fuc-4 3A3-Ker-8,3A3-Ker-9 3A3-Moo-5 3A3-Wol-6 3A4-Abr-2 3A4-Cen-1 3A4-Fre-13 3A4-Gar-15 3A4-Gre-9 3A4-Kha-14 3A4-Loz-16 3A4-Mar-5 3A4-Nie-4 3A4-Pit-7 3A4-Rao-12 3A4-Ros-11 3A4-Tav-3 3A4-Vaz-8 3A4-Whe-6 3A4-Zie-10 3B8-Abr-12 3B-Boy-5 3B-Cav-17 3B-Coo-7 3B-Eys-19 3B-Fis-4 3B-Gil-18 3B-Gol-9 38-Gro-8 3B-Kal-15 3B-Kle-11 3B-Lau-10 3B-Loz-13 3B-Man-16 3B-Mat-14 3B-Mur-3 3B8-San-2 3B-Sch-6 3B-Ten-1 3C-Bib-10 3C-Coa-4 3C-Col-6 3C-Coo-17 3C-Cou-9 lviii Other Related Abstracts Joshi Koppel Macher Marcusen Ognibene Pitchenik Tavitian Tenner-Racz Whiteside Mann Pitchenik Sandor Ultmann Winter Aiuti Biberfeld Boyko Chan Clauvel Dau Detels Frazer Greenspan Jaffe Kern Lazzarin Marche Marcusen Melbye Perrillo Abrams Anderson Auerbach Ball Boyko 3C-Jos-19 3D-Kop-7 3A2-Mac-5 3A4-Mar-5 3A1-0Ogn-4 3A4-Pit-7 3A4-Tav-3 3B-Ten-1 3A2-Whi-4 1B5-Man-2 1A5-Pit-3 3B-San-2 1A4-Ult-6 3E-Win-5 1B4-Aiu-3 3C-Bib-10 1C3-Boy-2 3E-Cha-6 1B4-Cla-9 1C3-Dau-7 2A-Det-7 1B3-Fra-2 3A4-Gre-9 3C-Jaf-12 3A3-Ker-8 1A2-Laz-4 3C-Mar-18 3A4-Mar-5 3C-Mel-7 1C3-Per-4 3B-Abr-12 2C-And-1 2A-Aue-6 1A3-Bal-9 1C3-Boy-2,3B-Boy-5 LIC cont. 11D: VIE: Abstracts in Section Eyster Hersh Jaffe Jeffries Joshi Lane Mann Marche Mel bye Moss Stevens Taylor Weber Bishburg Ho Koppel Moskowitz Navia Nielsen Resnick Sharer Snider Whelan Wong Chan Ciobanu Dorsett 3C-Eys-13 3C-Her-15 3C-Jaf-12 3C-Jef-11 3C-Jos-19 3C-Lan-14 3C-Man-2 3C-Mar-18 3C-Mel-7 3C-Mos-16 3C-Ste-5 3C-Tay-1,3C-Tay-8 3C-Web-3 3D-Bis-1 3D-Ho-5 3D-Kop-7 3D-Mos-9 3D-Nav-2,3D-Nav-4 3D-Nie-8 3D-Res-6 3D-Sha-3 3D-Sni-11 3D-Whe-12 3D-Won-10 3g-Cha-6 3E-Cio-10 3E-Dor-3 Other Related Abstracts Budzko Centers for Disease Control Climent Cooper Cowan Curran Dorsett Feorino Fishbein Freeman Fultz Gerstoft Goedert Gold Groopman Hanrahan Jaffe Khadem Klein Kristal Lerner Lewis Mathur-Wagh Maul Melbye Moss Murray Niedt Pape Patow Peterman Ragni Rank i Sirianni Thomas Ziegler Perry Abrams Allain Ammann lix 7A-Bud-5 1B4-Cen-1 1B2-Cli-2 3B8-Coo-7,4B-Coo-6 2D-Cow-4 2C-Cur-25 3E-Dor-3 2C-Feo-14 3B-Fis-4 3A4-Fre-13 TA-Ful-1 1B4-Ger-5 1B1-Goe-5,1C1-Goe~-2 3B-Gol-9 3B-Gro-8 1A7-Han-6 1A1-Jaf-2,1A1-Jaf-3,2C-Jaf-13 3A4-Kha-14 3B-Kle-11 1B1-Kri-4 3A2-Ler-3 3E-Lew-4 3B-Mat-14 7A-Mau-6 1A1-Mel -4 1B1-Mos-7 38-Mur-3 3A4-Nie-4 1B2-Pap-3 3A1-Pat-7 2C-Pet-8 1A3-Rag-4 1C3-Ran-9 1B4-Sir-2 1A4-Tho-7 2G-Zie-3,3A4-Zie-10 4A-Per-2 3A4-Abr-2 1A3-Al 1-15 1A4-Amm-4 IIE: cont, IF: IVA: IVB: Abstracts in Section Fahey Jothy Kekow Lewis Rodman Schrof f Siegel Winter Archibald Fujikawa Groopman Lecatsas Dilley Perry Centers for Disease Control Cooper Gordin Haverkos 3E-Fah-9 3E-Jot~-7 3E-Kek-8 3E-Lew-4 3E-Rod-1 3E-Sch-11 3E-Sie-2 3E-Win-5 3F-Arc-1 3F-Fuj-2 3F-Gro-4 3F-Lec-3 4A-Di | -1 4A-Per-2 4B-Cen-8,4B-Cen-10 4B-Coo-6 4B-Gor-7 4B-Hav-9 1x Other Related Abstracts Biberfeld Birx Boyko Brown Cavaille-Col | Chali foux Clumeck Daly Daniel Daul deShazo Detels Fishbein Fuchs Gascon Gerstoft Gilmore Giudizi Goedert Hanrahan Hauser Hedenskog Hersh Kalish Kern Khadem Lane Lazzarin Mathur-Wagh Maul Mittelman Murray Perrillo Rank i Rinaldo Schechter Taylor Volberding Centers for Disease Control Fultz Ho Salahuddin Abrams Bishburg Kovacs Navia Ognibene 2C-Bib-10,3C-Bib-10 1C3-Bir-6 3A3-Boy-2 1C2-Bro-2 3B-Cav-17 7A-Cha-11 1B5-Clu-11 1A3-Dal-12 1A3-Dan-5 1C3-Dau-7 1A3-deS-17 1C3-Det-14,2A-Det-7 3B-Fis-4 3A3-Fuc-4 2C-Gas-24 1A1-Ger-7,1B4-Ger-5 3B-Gil-18 2C-Giu-6 2A-Goe-4 1A7-Han-6 4C2-Hau-10 5B1-Hed-5 3C~Her~15% 3B-Kal-15 3A3-Ker-8,3A3-Ker-9 3A4-Kha-14 3C-Lan-14 1A2-Laz-4 3B-Mat-14 7A-Mau-6 3A1-Mit-2,4C2-Mit-15 3B-Mur-3 1C3-Per-4 1C3-Ran-9 1C3-Rin-3 1C3-Sch-10 3C-Tay-8 3A1-Vol-9 2D-Cen-1 TA-Ful-1 3D-Ho-5 5B2-Sal-10 3A4-Abr-2 3D-Bis-1 3A2-Kov-2 3D-Nav-4 3A1-0Ogn-4 VB: cont. IVC): IVC2: VAL: VA2: Abstracts in Section Jaffe Leoung Mintzer Stahl-Bayliss Volberding Wharton Broder Cooney Gold Grieco Groopman Koretz McCormick Tsang Vrang Bonavida Clumeck Fauci Frederick Ge Imann Hauser Ho Lane Lotze Mittelman Pomp i dou Preble Rook Valone Volberding DiClimente Morton Silvestre Williams Centers for Disease Control Emmons Feldman Friedman Martin McKusick Siegel 4B-Jaf-11 4B-Leo-1 4B-Min-5 4B-Sta-3 4B-Vol-4 4B-Wha-2 4C1-Bro-4 4C1-Coo-3 4C1-Gol-8 4C1-Gri-6 4C1-Gro-7 4C1-Kor-2 4C1-McC-5 4C1-Tsa-9 4C1-Vra-1 4C2-Bon-1 4C2-Clu-9 4C2-Fau-5 4C2-Fre-4 4C2-Gel-6 4C2-Hau-10 4C2-Ho-7 4C2-Lan-11 4C2-Lot-12 4C2-Mit-15 4C2-Pom-2 4C2-Pre-3 4C2-Roo-8 4C2-Val-13 4C2-Vol-14 5A1-DiC-4 5A1-Mor-3 5A1-Sil-1 SA1-Wil-2 5A2-Cen-6 SA2-Emm-1 5A2-Fel-5 5A2-Fri-2 5A2-Mar-3 5A2-McK-7 5A2-Sie-4 1xi Other Related Abstracts Siegel Volberding Wheat Whelan Whiteside Wol Ischlager Wong Ziegler Fauci Ge lmann Volberding Groopman Centers for Disease Control Feldman Siegel Bloom Centers for Disease Control Contreras Des Jarlais Jaffe Kreiss Mayer Pindyck Silvestre Stall 3E-Sie-2 3A1-Vol-9 3A4-Whe-6 3D-Whe-12 3A2-Whi-4 3A3-Wol-6 3D-Won-10 3A4-Zie-10 4C2-Fau-5 4C2-Gel-6 4C2-Vol-14 4C1-Gro-7 2A-Cen-1 5A2-Fel-5 5A2-Sie-4 1A3-Blo-14 1A7-Cen-4,2A-Cen-1 5B82-Con-7 1A2-Des-1 1A1-Jaf-2 1A6-Kre-1 1C1-May-1 582-Pin-9 5A1-Sil-1 1C2-Sta-1 VB1: VB2: VB3: VC: VIA: VIB: VIC: VIIA: Abstracts in Section Abb 5B81-Abb-3 Barrett 5B1-Bar-2 Carlson 5B1-Car-10 Fang 581-Fan-4 Hedenskog 5B81-Hed-5 Kuhn 5B81-Kuh-6 Mortimer 5B1-Mor-9 Parry 581-Par-7 Peetoom 5B1-Pee-8 Rees ink 5B1-Ree-1 Schupbach 5B1-Sch-11 Weiss 5B1-Wei-12 Contreras 5B2-Con-7 Gallo 5B2-Gal-11 Groopman 5B2-Gro-1 Lindhardt 582-Lin-3 Mayer 582-May-2 McDougall 5B2-McD-8 Nusbacher 5B2-Nus-4 Pindyck 5B2-Pin-9 Ross 5B82-Ros-6 Salahuddin 5B2-Sal-10 Sayers 5B2-Say-5 Hil fenhaus 5B3-Hil-2,5B3-Hi | -4 Jungkind 583-Jun-1 Quinnan 5B83-Qui-3 Martin 5C-Mar-2 Resnick 5C-Res-1 Spire 5C-Spi-3 Steinbrook 6A-Ste-1 Hardy 6B-Har-3 Scitovsky 6B-Sci-1 Seage 6B-Sea-2 Alter TA-Alt-7 Budzko 7A-Bud-5 Chali foux 7A-Cha-11 Fultz TA=Ful-=1 Gravel | TA-Gra-9 Henrickson TA-Hen-13 Kank i TA-Kan-2,7A-Kan-4 Letvin TA-Let-12 Marx TA-Mar-8 Mau | 7A-Mau-6 1xii Other Related Abstracts Groopman Jungkind Kuritsky Lindhardt Peterman Centers for Disease Control Desmyter Ho Kuritsky Laurence Peterman Schupbach Dienstag Hunsmann Jason Kitchen Siegel Wood Fujikawa Hirsch Lozada Feldman Barin Kank i 5B2-Gro-1 583-Jun-1 1A7-Kur-5 582-Lin-3 2C-Pet-4 1A7-Cen-3,1B4-Cen-1 1A7-Des-1 3D-Ho-5 1A7-Kur-5 3B-Lau-10 2C-Pet-8 5B81-Sch-11 2C-Die-12 1B4-Hun-7 1A3-Jas-8 2C-Kit-21 3E-Sie-2 2C-Woo-2 3F-Fuj-2 2E-Hir-6 3A4-Loz-16 5A2-Fel -5 7B8-Bar-2 7B-Kan-1 VIIA: cont. VIB: Abstracts in Section Osborn Tsai Barin Kank i 7A-0sb-10 7TA-Tsa-3 7B-Bar-2 7B-Kan-1 Ixdiii Marx 7A-Mar-8 [. Prevalence and Spread of AIDS/HTLV-III/LAV A. Population Studies and Groups at Risk I. Homosexual Males » Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Collier, Ann C., MD; Barnes, Robert C., MD; Handsfield, H. Hunter, MD. Prevalence of Antibody to LAV/HTLV-III Among Homosexual Men in Seattle. American Journal of Public Health, May 1986, Vol. 76, No. 5: 564-565. Department of Medicine, University of Washington; Seattle-King County Department of Public Health; Seattle Gay Clinic, Seattle, Washington. This study evaluated homosexual men attending a gay clinic or a sexually transmitted disease (STD) clinic in Seattle in early 1985 to determine the prevalence of antibodies to lymphadenopathy-associated virus/human T- cell lymphotropic virus type III (LAV/HTLV-III). Prevalence ranged from 32% at the community clinic to 42% at the STD clinic. Among 20 homosexual subjects with a history of intravenous (I.V.) drug abuse, 11 (55%) were seropositive, compared with 47 (32%) of the 148 non-drug- using men. Positive tests were apparently not related to age or to number of lifetime sexual partners. This was an epidemiologic study of antibody levels in homosexual men in Seattle and the relationship of LAV/HTLV-III antibodies to demographics and risk factors for AIDS. Subjects were recruited from men having routine evaluations at two clinics. A group of 76 heterosexual subjects were also recruited from the STD clinic. An initial interview covered basic demographics and information about sexual activity (including number of lifetime sexual partners) and L.V. drug use. Antibodies to LAV/HTLV-III were determined by enzyme-linked immunosorbent assay with two commercially available methods; positives were confirmed by retesting with the second method. (All positives were reactive by both methods.) A total of 168 homosexually active men being treated in a gay community clinic (59) or a Seattle STD clinic (109) were studied in early 1985. The STD clinic homosexuals had a mean age of 29.8 years, 83% of them were white, and their median number of lifetime sexual partners fell in the 100 to 199 range; 14 (13%) were L.V. drug users. The gay community clinic homosexuals had a mean age of 32.4 years, 87% of them were white, and their median number of lifetime sexual partners fell in the 100 to 199 range; six (11%) were [.V. drug users. The STD clinic heterosexuals had a mean age of 28.7 years, 81% of them were white, and their median number of lifetime sexual partners fell in the 10 to 49 range; 16 of 72 (17%) were L.V. drug users. 1) Populations: Homosexuals, I.V. Drug Abusers, Heterosexuals (IA 1,2,6), 2) Cofactors: Other STDs (IC3) 1A1-Col-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jaffe, Harold W., MD; Hardy, Ann M., DrPH; Morgan, W. Meade, PhD; Darrow, William W., PhD. The Acquired Immunodeficiency Syndrome in Gay Men. Annals of Internal Medicine, November 1985, Vol. 103, No. 5: 662-664. AIDS Branch, Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. This article summarizes recent research findings for AIDS and the homosexual male population. In a sample of a gay cohort enrolled in a San Francisco clinic, 2.7% of the men had AIDS and 26% had related conditions in 1984. Antibody to human T-cell lymphotropic virus type III (HTLV-II) was found in 67% of the men, including 58% of the asympto- matic men. Up to 20% of gay men with generalized lymphadenopathy developed AIDS. Behavioral factors associated with an increased risk of AIDS include many sexual partners, receptive anal intercourse, and "fisting." Trends in cases of AIDS in gay men and other adults can be examined by estimating statistically the time in which the number of cases can be expected to double. This is done by projecting the current number of cases, first adjusting the numbers for reporting delays. The projected doubling time of cases of AIDS in gay men is found to be slightly shorter than that for other adult cases. In fact, the doubling time of cases for gay men in New York City is significantly longer than in San Francisco or elsewhere. This may mean that most New York City men at highest risk have by now already been infected with HTLV-III, or this trend could reflect changed sexual practices for this group. In 1984, the national incidence of AIDS in men over the age of 15 who never married was 13 per 100,000 population. The incidence rate in Manhattan was 258 per 100,000, and in San Francisco it was 329 per 100,000. The years of potential life lost due to AIDS was estimated in 1984 to rank just below that for cancer for men aged 25 to 44 who never married. In Manhattan and San Francisco, AIDS was ranked as the leading cause of years of potential life lost. This article summarizes recent research findings for AIDS and the homosexual male population. Results are presented for several study samples from studies conducted by the Centers for Disease Control. Surveillance and cohort study data are used. 1) Populations: Homosexuals (IAl), 2) Geographic Trends: U.S. (IBl), 3) Transmission: Sexual Activity (IIA), 4) Disease Stages (Future Incidence) (IIIC), 5) Information/Education: Risk Behaviors and Protection (VA2) 1A1-Jaf-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jaffe, Harold W., MD; Darrow, William W., PhD; Echenberg, Dean F., MD, PhD; O'Malley, Paul M., BA; Getchell, Jane P., DrPH; Kalyanaraman, V.S., PhD; Byers, Robert H., PhD; Drennan, David P., MD; Braff, Erwin H., MD; Curran, James W., MD; Francis, Donald P., MD, DSc. The Acquired Immunodeficiency Syndrome in a Cohort of Homosexual Men: A Six-Year Follow-Up Study. Annals of Internal Medicine, August 1985, Vol. 103, No. 2: 210-214. AIDS Branch, Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; Department of Public Health, City and County of San Francisco, California. A cohort of 6,875 homosexual men, initially seen at the San Francisco City Clinic between 1978 and 1980, was studied to determine the incidence and prevalence of AIDS and related conditions and infection with human T-cell lymphotropic virus type III/lymphadenopathy- associated virus (HTLV-III/LAV). By December 1984, 2.4% of the men had AIDS; mortality attributable to AIDS in 1984 was 600 deaths per 100,000. For each man with AIDS in a representative sample of 474 cohort members seen in 1984, 7.5 men had generalized lymphadenopathy, 1.1 had other pre-AIDS findings, and 0.8 had immunologic abnormalities. Prevalence of antibodies to HTLV- III/LAV increased from 4.5% in 1978 to 67.4% in 1984. Of 31 persons whose blood tests were positive but who did not have AIDS between 1978 and 1980, 2 developed AIDS, and 8 others developed related conditions during an average 61 months of follow-up. Over a 6-year period, two- thirds of the cohort members were infected with HTLV-III, and almost one-third developed conditions related to AIDS. This was a cohort study of homosexual and bisexual men in San Francisco. Subjects were originally enrolled in studies of hepatitis B; basic demographic data and blood specimens were obtained in 1978-80, and the blood sera were frozen. Participants in the 1984 follow-up study were interviewed and examined for signs of AIDS or related conditions; blood specimens were also obtained. For follow-up participants both blood specimens were tested for antibodies to HTLV-III/LAV by enzyme- linked immunosorbent assay, and dubious specimens were retested. Cases of AIDS among cohort members were reported through the city's health department. A cohort of 6,875 homosexual and bisexual men, initially seen at the San Francisco City Clinic between 1978 and 1980 and treated for sexually transmitted diseases, was studied. A subset of 474 men from a representative sample of 785 men in this cohort participated in the follow-up study. 1) Populations: Homosexuals (IAl), 2) Incubation Period and Disease Stages (IIIC) 1A1-Jaf-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Melbye, Mads; Biggar, Robert J.; Ebbesen, Peter; Sarngadharan, M.G.; Weiss, Stanley H.; Gallo, Robert C.; Blattner, William A. Seroepidemiology of HTLV-III Antibody in Danish Homosexual Men: Prevalence, Transmission, and Disease Outcome. British Medical Journal, 8 September 1984, Vol. 289: 573-575. Institute of Cancer Research, Radiumstationen, Aarhus, Denmark (Melbye, Ebbesen); Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland (Biggar, Weiss, Blattner); Department of Cell Biology, Litton Bionetics Inc., Kensington, Maryland (Sarngadharan); Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Gallo). To examine the introduction of human T-cell lymphotropic virus type III (HTLV-II) into an area where the risk of developing AIDS was initially low, Danish homosexual men were studied for extent of exposure, means of transmission, and relationship between seroconversion and subsequent illness. Antibody to HTLV-III was present in 22 (8.8%) of 250 men, as well as in the blood of two known AIDS patients. A positive antibody test was most strongly associated with sexual exposure to homosexual men during visits to the U.S. Increased frequency of receptive anal intercourse was also significantly associated with HTLV-III infection. Age, years of homosexual experience, number of homosexual partners, and use of nitrite inhalants, however, were not statistically significant independent risk factors. Of these 22 men, 2 (9%) developed AIDS and 2 others (9%) developed AIDS-related complex (ARC) within the study's 2- year time frame. During the period from December 1981 to February 1983, roughly 1% of the sample men per month converted from HTLV-III- negative to HTLV-IIl-positive status. The hypothesis that HTLV-III is causally related to the development of AIDS is supported by the observed spread of HTLV-II from high- to low-risk areas and the subsequent appearance of AIDS and ARC in the HTLV-III-positive group. This study is based on blood samples and a self-administered questionnaire about lifestyle collected in 1981 as part of a prospective study of AIDS; 40 subjects were examined and reinterviewed in April 1982 and February 1983. Antibody to HTLV-II in blood samples was measured by enzyme-linked immunosorbent assay, with a ratio of sample to background of 5 or more as the criterion for seropositivity. Borderline cases with ratios between 3 and 5 were excluded from comparison. Statistical comparisons were made between HTLV-III-positive and HTLV- [[I-negative groups on lifestyle elements and clinical outcome. A total of 259 Danish men (170 from Copenhagen and 89 from Aarhus, another smaller port city) were enrolled in the study through the auspices of a national organization of homosexuals. Blood serum samples were available for 250 men whose mean age was 32.9 years, who reported an average of 12.1 years of homosexual experience, and who had an average of 22.2 (median, 10) sex partners a year. A subset of 40 men were examined and reinterviewed in April 1982 and February 1983. The matched (for age and sex) control group consisted of Danish blood 1A1-Mel-4 donors. Two of the first three AIDS patients in Denmark were also interviewed. Policy Keys: 1) Populations: Homosexuals (IAl), 2) Geographic Trends: Europe (Denmark) (IB4), 3) Disease Progression (IIIC), #4) Cofactors: Demographic, Drug-Related, Other Infections (IC1,2,3) Author(s): Title: Source: [nstitution: Findings: Guinan, Mary E., MD, PhD; Thomas, Pauline A., MD; Pinsky, Paul F., MPH; Goodrich, James T., MD; Selik, Richard M., MD; Jaffe, Harold W., MD; Haverkos, Harry W., MD; Noble, Gary, MD; Curran, James W., MD, MPH. Heterosexual and Homosexual Patients with the Acquired Immunodefi- ciency Syndrome: A Comparison of Surveillance, Interview, and Laboratory Data. Annals of Internal Medicine, February 1984, Vol. 100, No. 2: 213-218. AIDS Activity, Center for Infectious Diseases, Division of Venereal Disease Control, Center for Prevention Services, Centers for Disease Control, Atlanta, Georgia; New York City Department of Health, New York, New York. Surveillance data show that, of the 377 patients with AIDS whose cases were reported as of | June 1982, 80% were homosexual or bisexual men, 17% were heterosexual men and women, and 3% were of unknown sexual orientation. Of the 64 heterosexual patients, 61% were intravenous (I.V.) drug users, 25% were Haitian, and 14% had no identified risk factor. White patients composed a significantly greater proportion of the homosexual-bisexual group than any other risk group. Most [.V. drug users (72%) and patients with no identified risk factor (56%) were black (non-Haitian) or Hispanic. Kaposi's sarcoma affected a significantly higher proportion of homosexual patients (34%) than of other risk groups. Pneumocystis carinii pneumonia was significantly more frequent in I.V. drug users 77%) than in homosexuals (44%). Other opportunistic infections were found significantly more often in Haitians than in other risk groups. Patients with both Kaposi's sarcoma and P. carinii pneumonia were almost exclusively homosexual and bisexual men (98%). Interview data showed that homosexual patients had a greater number of years of schooling, whereas heterosexual patients were more likely to have been married and less likely to earn $20,000 or more per year or to have a sexually transmitted disease. Homosexual men only had a history of ever having inhaled cocaine, nitrites, and ethyl chloride; a history of marijuana use was common among all risk groups. Heterosexual patients reported fewer lifetime and year-prior-to-illness sexual partners than did homosexuals. Few heterosexual patients were exposed to feces during sex or had rectal trauma. Laboratory data showed that antibody to cytomegalovirus (CMV) in patients with P. carinii pneumonia was significantly higher for homosexual men than for [.V. drug users. Only one homosexual patient with P. carinii pneumonia was negative for Epstein-Barr virus antibody. A significantly greater portion of homosexuals (52%) than heterosexuals (8%) had positive tests for the organism causing syphilis. There were no significant differences in rates of hepatitis A and hepatitis B between heterosexuals and homosexuals or among different diagnoses. 1A1-Gui-5 Method: Sample Size: Policy Keys: Risk factors for acquisition of AIDS are different for heterosexual and homosexual patients; studies should always include analyses by risk group and diagnosis. In this mixed-modality study, similarities and differences between homosexual and heterosexual AIDS patients were assessed in terms of demographic and behavioral characteristics, as well as blood test evidence for infection. Blood tests were done for antibodies to cytomegalovirus, Epstein-Barr virus, and herpes simplex viruses type 1 and type 2 and for syphilis, hepatitis A, and hepatitis B, as well as for serum immunoglobulin levels. Surveillance data from 377 AIDS patients reported to the Centers for Disease Control (CDC) as of | June 1982. Thirty-one of the 64 heterosexual patients (who constituted 17% of the total) were interviewed--24 men and 7 women, 22 of whom were [.V. drug users, 4 of whom were Haitian, and 5 of whom had no identified risk factor. Laboratory tests were performed on specimens from 100 homosexual men, 50 from the CDC's national case control study of homosexual men and 50 who were dead or too ill to be interviewed, and 35 heterosexual patients (27 of those interviewed and 8 who were deceased). 1) Populations: Homosexuals, I.V. Drug Users, Minorities, Heterosexuals, (IA1,2,5,6), 2) Geographic Trends: U.S. (IBl), 3) Cofactors: Risk Group and Diagnosis (IC4), 4) Cofactors: Other Infections (IC3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Fauci, Anthony S., MD; Macher, Abe M., MD; Longo, Dan L., MD; Lane, H. Clifford, MD; Rook, Alain H., MD; Masur, Henry, MD; and Gelmann, Edward P., MD. Acquired Immunodeficiency Syndrome: Epidemiologic, Clinical, Immuno- logic, and Therapeutic Considerations. Annals of Internal Medicine, January 1984, Vol. 100, No. 1: 92-106. National Institutes of Health, Bethesda, Maryland. This article summarizes findings and thinking about AIDS to date. AIDS is a new disease of unknown cause, but it is almost surely due to a transmissable agent, most likely a virus. The disease is clearly spread by sexual contact, particularly homosexual activity. The other major recognized form of spread of AIDS is blood-borne transmission; it seems unlikely that the disease is spread via casual, nonsexual, nonblood routes. Although at present AIDS is still highly concentrated in the U.S., it is now found in several countries throughout the world. The common denominator of the disease is a profound suppression of cell-mediated immunity, specifically a reduction in the number and quality of helper T cells. Hyperactivity of B lymphocytes is also a characteristic of AIDS. Clinical manifestations of AIDS are severe and life-threatening opportunistic infections and unusual malignancies, particularly Kaposi's sarcoma. The AIDS mortality rate approaches 100%, making it one of the most extraordinary transmissable diseases in history. This article is an edited summary of a conference of the Combined Clinical Staffs at the Clinical Center, Bethesda, Maryland, on 23 June 1983, sponsored by the National Institutes of Health. A total of 2,008 U.S. AIDS cases had been reported to the Centers for Disease Control by August 1983. These patients are 58% white non- Hispanic, 27% black non-Hispanic, and 14% Hispanic. The age distribution shows that virtually all AIDS patients are 20 to 49 years old. The 1,878 male cases included 1,427 homosexuals or bisexuals, 273 intravenous (I.V.) drug users, 91 Haitians, 15 hemophiliacs, and 72 with no apparent risk factor. The 130 female cases included 66 I.V. drug users, 14 Haitians, and 50 with no apparent risk factor. 1) Populations: Homosexuals, I.V. Drug Users, Minorities, Hemophiliacs, Heterosexuals (IA 1,2,3,5,6,), 2) Geographic Trends: U.S. (IB1) 1A1-Fau-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Gerstoft, Jan; Peterson, Carsten S.; Kroon, Susanne; Ullman, Susanne; Bentsen, Kirsten; Dickmeiss, Ebbe; Nielsen, Jens Ole; Mogens, Hans; Andersen, Kerzel; Lorenzen, Ib. T Lymphocyte Subsets in Homosexual Men from Copenhagen. European Journal of Clinical Investigation, 1984, Vol. 14: 301-305. Rubella Department, Statens Seruminstitut, Copenhagen; Department of Medicine, Divisions of Rheumatology and Hepatology, Department of Clinical Immunology and Department of Dermatology, Hvidovre Hospital, University of Copenhagen; Department of Infectious Diseases and Department of Dermatology, Rigshospital, University of Copenhagen; Institute of Medical Microbiology, University of Aarhus, Denmark. This study assessed the immunological status of homosexual men in Denmark, a country with one of the highest incidences of AIDS in Europe. Immunological abnormalities observed in a screening of 66 asymptomatic homosexual men from Copenhagen included low helper/suppressor T-cell ratios, due to increases in the suppressor type of T cells. Homosexuals with many partners and those who had been sexual partners of AIDS patients had lower ratios than those without these fea- tures. Cytomegalovirus (CMV) was isolated from 15% of patients, but in only 3% of controls, and this was associated with patients' lower T-cell ratios. In this case-control study, immunological studies were conducted on blood samples from all subjects. Subjects completed a questionnaire concerning sexual behavior, previous diseases, travels, and drug abuse. Tests for CMV antibody were conducted on urine and sputum samples. Sixty-six homosexual men visiting two venereal disease (VD) clinics in Copenhagen between October 1982 and May 1983 were studied, each having had two or more episodes of VD. Patients with current infections (including VD) or suspected AIDS were excluded from the study. Controls were 31 apparently healthy, age-matched male doctors and medical students. 1) Populations: Homosexuals (IAl), 2) Immunological Aspects (IIE), 3) Geographic Trends: Europe (Denmark) (IB4) 1Al1-Ger-7 [. Prevalence and Spread of AIDS/HTLV-III/LAV A. Population Studies and Groups at Risk 2. L.V. Drug Users Author(s): Title: Source: [nstitution: Findings: Method: Des Jarlais, Don C., PhD; Friedman, Samuel R., PhD; Hopkins, William, MA. Risk Reduction for the Acquired Immunodeficiency Syndrome Among Intravenous Drug Users. Annals of Internal Medicine, November 1985, Vol. 103, No. 5: 755-759. New York State Division of Substance Abuse Services and Narcotic and Drug Research, Inc., New York City, New York. Intravenous (I.V.) drug users are the second largest risk group for AIDS and may be a bridge to two other groups: children and heterosexual partners of drug users. In the absence of effective treatment or vaccines, control of AIDS among drug users must rely on efforts to reduce needle sharing (the mode of transmission). The traditional image of L.V. drug users, however, does not promise great progress in reduction of this risk. This article reviews characteristics of AIDS as a disease that impede efforts at risk reduction among drug users and reports on current risk reduction efforts among drug users in New York City. Of a total of 260 [.V. drug users screened for immunologic findings, 160 were positive for antibody to human T-cell lymphotropic virus type III/lymphadenopathy- associated virus (HTLV-III/LAV). In 1984, self-reported prevalence of AIDS-related symptoms for the previous 5 years was examined in 82 I.V. drug users who were seronegative for HTLV-II[/LAV and 136 antibody- positive I.V. drug users. Symptoms were common even among drug users who had not been exposed to HTLV-III[/LAV, and they rose to significantly higher levels only in the one-third of antibody-positive drug users who had immunologic abnormalities. In another study, conducted during the fall of 1983, extensive interviews were carried out with 18 I.V. drug users who were not in treatment. They had all heard of AIDS and believed it was spread through sharing needles. They also reported an increased demand for "new" needles among I.V. drug users. To study the demand for new needles, interviews were conducted with persons selling needles on the street, during the spring of 1985. Eighteen of 22 (82%) needle sellers reported that new-needle sales had increased over the past year. They reported an average profit of $2 on each new needle. When asked the reasons for the increased demand for new needles, 6 of the 18 reported general increased demand and 4 specifically mentioned AIDS. Ten of 21 reported that they also sold used needles. Seven of these 10 reported that they had resealed used needles and sold them as new. Findings are reported from several surveys conducted to examine the self-reported prevalence of AIDS-related symptoms, immunologic status and risk reduction for AIDS among [.V. drug users. Blood testing was performed and surveys were conducted for several groups of [.V. drug users for separate studies. Immunologic studies and reports of self- reported prevalence and immunologic status were obtained from [.V. drug users in treatment programs. 1A2-Des-1 Sample Size: Policy Keys: Interviews with drug addicts and with persons selling needles to drug addicts were conducted by the Street Research Unit of the Bureau of Research of the New York State Division of Substance Abuse Services. Interviews with drug users were conducted at an ethnographic research storefront in a New York City neighborhood with a high level of [.V. drug abuse, where drug users are often recruited and are usually paid a small fee for their time to provide data from the perspective of the current drug user (which may differ from that of drug users in treatment). Inter- views with needle sellers were conducted by identifying such persons "hawking" needles on the streets of New York City. Study subjects included 260 I.V. drug users and 218 [.V. drug users, both groups from treatment centers in New York City, and 18 I.V. drug users and 22 needle sellers from the streets of New York City. 1) Populations: [.V. Drug Users (IA2), 2) Education/Information: Risk Behaviors and Protection (VA2), 3) Transmission: [.V. Drug Abuse (IIB) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Friedland, Gerald H., MD; Harris, Carol, MD; Butkus-Small, Catherine, MDs; Shine, Daniel, MD; Moll, Bernice, PhD; Darrow, William, PhD; Klein, Robert S., MD. Intravenous Drug Abusers and the Acquired Immunodeficiency Syndrome (AIDS): Demographic, Drug Use, and Needle-Sharing Patterns. Archives of Internal Medicine, August 1985, Vol. 145, No. 8: 1413-1417. Division of Infectious Diseases, Department of Medicine (Friedland, Harris, Butkus-Small, Klein), Department of Social Medicine (Shine), Division of Immunopathology, Department of Pathology (Molle), Montefiore Medical Center, North Central Bronx Hospital, and Albert Einstein College of Medicine, Bronx, New York; AIDS Activity, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Darrow). In this study, demographic characteristics, drug use patterns, and sexual habits of intravenous (I.V.) drug abusers were examined to further define this population at risk for AIDS. The subjects in each of two groups (subjects with AIDS or AIDS-related complex (ARC) and without AIDS or ARC) were similar demographically, in drug use practice, in sexual orientation, and in sexual experience. Of the AIDS and ARC patients, 34 of 40 (88%), including all 7 homosexual men, shared needles, as did all 14 subjects without AIDS or ARC. Of all the patients, 74%, including all homosexual men, attended shooting galleries. Needle sharing supports the hypothesis of AIDS transmission by blood; this is the logical link between [.V. drug abusers and male homosexuals in the two largest groups with AIDS. All subjects were interviewed about demographic characteristics and sexual and drug use practices. All subjects were given a physical examination and underwent an immunologic laboratory screening evaluation, including lymphocyte count, immunoglobulin levels, testing for skin hypersensitivity, and quantitation of T-cell subsets by fluorescence with OKT3, OKT#4, and OKT8 monoclonal antibodies. The subjects studied consisted of 40 I.V. drug abuser patients with AIDS (16) or ARC (24) who were identified during hospitalization at three New York hospitals (Montefiore Medical Center, North Central Bronx Hospital, or Bronx Municipal Hospital Center) from July 1981 to March 1983. A comparison control group of 14 I.V. drug abusers with no evidence of AIDS or ARC who were hospitalized for illnesses unrelated to AIDS or who enrolled in the Montefiore Medical Center Drug Abuse Treatment Program were also studied. 1) Populations: [.V. Drug Abusers (IA2), 2) Transmission [.V. Drug Abuse- (IIB) 1A2-Fri-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Crovari, P. Cuneo; Terragna, A.; Robert, L.; Orlando, G.; Rizzo, F.; Piuma-Fusco, M.; Icardl, G.C. Papa, Dg DiPonzio, A. Auteri, G4 Mazzoleni, C.; Crovari, P. Increasing Prevalence of HTLV-III Infection in Intravenous Drug Users in Liguria, Italy. Bollettino Dell Istituto Sieroterapico Milanese, 1985, Vol. 64, No. 4: 339- 342. Institute of Hygiene of the University of Genoa (P.C. Crovari, Piuma- Fusco, Icardi, DiPonzio, Auteri, Mazzoleni); First Clinic of Infectious Disease of University of Genoa (Terragna); Regional Hospital of Genoa, Infectious Disease Division (Robert, Rizzo); Hospital of Sanremo, Infectious Disease Division, Sanremo, Italy (Orlando, Papa). This study describes the change in the prevalence of antibody to human T-cell lymphotropic virus type III (HTLV-II) in Italian intravenous ([.V.) drug users over the period 1980 to 1985 and presents data on the prevalence of HTLV-II antibody among hospital staff and other groups that are likely to have contact with drug users or their blood and in two control groups of the general population in 1982 and 1984, respectively. No LV. drug abuser was HTLV-II positive in 1981; from 1982 to 1984 there was a strong increase in the prevalence of HTLV-II antibodies: 2% in 1981, 22% in 1983, and 39% in 1984. The prevalence remained about 40% in early 1985. None of the controls have tested positive for HTLV- [Il antibodies, although one family contact (wife of an HTLV-Ill-positive drug abuser) did test positive. This was a case-control study with prospective testing for HTLV-III antibodies. Blood serum samples from 683 [.V. drug abusers were obtained over the period May 1981 to March 1985. For prospectively studied 1.V. drug abusers, blood serum specimens were collected for each year, starting with 1981. All serum samples were stored frozen. Antibodies to HTLV-II were determined by enzyme-linked immunosor- bent assay, with doubtful reactive specimens retested by Western blot. A total of 683 intravenous drug users in Liguria, Italy, were studied between May 1981 and March 1985; also, 68 L.V. drug abusers (53 from Genoa and 15 of the Sanremo area) were studied prospectively, and 147 other subjects tested included 91 hospital staff, 32 workers in a therapeutic community for drug users and 24 family contacts of HTLV- [[I-positive drug users. Two control groups were selected from the general population (256 in 1982 and 538 in 1984). 1) Populations: 1.V. Drug Abusers (IA2), 2) Geographic Trends: Europe (Italy) (IB4), 3) Populations: Health Care Workers, Heterosexuals (IA7,6), 4) Transmission: [.V. Drug Abuse, Sexual Activity (IIB,A) 1A2-Cro-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lazzarin, A.; Galli, M.; Introna, M.; Negri, C.; Mantovani, A.; Mella, L.; Ferrante, P.; Parravicini, C.; Trombini, M.; Aiuti, F.; Moroni, M.; Zanussi, C. Outbreak of Persistent, Unexplained, Generalized Lymphadenopathy with Immunological Abnormalities in Drug Addicts in Milan. Infection, 1984, Vol. 12, No. 6: 372-376. Clinica delle Malattie Infettive, Universita di Milano, Milan (Lazzarin, Galli, Negri, Moroni); Istituto di Ricerche Farmacologiche Mario Negri, Milan (Introna, Mantovani); Centro per Assistenza alle Tossicodi- pendenze, Ospedale "L. Sacco", Milan (Mella, Trombini); Istituto di Virologia, Universita di Milano, Milan (Ferrante); Cattedra di Anatomia e Istologia Patologica V, Universita di Milano, Milan (Parravicini) Cattedra di Immunologia Clinica, Universita di Roma, Rome (Aiuti); Clinica Medica II, Universita di Milano, Milan, Italy (Zanussi). Persistent unexplained lymphadenopathy with intermittent fever, weight loss, night sweats, and malaise was monitored from March to October 1983 in 16 of 133 Italian intravenous drug addicts. The subjects showed immunological alterations, including lymphopenia, decreased helper/sup- pressor T-cell ratio, decreased natural killer cell activity, loss of or lowered reactivity to skin sensitivity testing, and increased levels of immunoglobulin G. Antibodies to human T-cell lymphotropic virus type III (HTLV-II) were found in 14 of the 16 patients with lymphadenopathy and in 3 of Il symptom-free drug addicts. By and large, the symptom- free drug addicts had a condition resembling that previously described for a group of nonsymptomatic homosexual men. At this time only a few cases of AIDS have been observed in Italy. The Center for Drug Addicts Assistance in Milan, Italy, had been following 133 intravenous drug addicts on methadone maintenance for at least 2 years. Drug addicts with persistent, unexplained lymphadeno- pathy were studied, while symptom-free drug addicts and healthy subjects were used as controls. Various aspects of their immune systems were tested by standard methods. Sixteen male drug addicts with lymphadenopathy syndrome lasting for 3 months or more served as subjects. Eleven symptom-free drug addicts from the same center and 12 healthy subjects who were age- and sex- matched served as controls. All of the drug addicts lived in a restricted suburban area and indulged in frequent heterosexual and homosexual intercourse and intravenous drug practices. 1) Populations: [.V. Drug Users (IA2), 2) Precursors of AIDS (IIIB), 3) Geographic Trends: Europe (Italy) (IB4), 4) Immunological Aspects (IIE) 1A2-Laz-4 I. Prevalence and Spread of AIDS/HTLV-III/LAV A. Population Studies and Groups at Risk 3. Hemophiliacs el Author(s): Titles Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Surveillance of Hemophilia-Associated Acquired Immunodeficiency Syndrome. Morbidity and Mortality Weekly Report, 31 October 1986, Vol. 35, No. 43: 669-671. Centers for Disease Control, Atlanta, Georgia. As of 15 September 1986, 238 cases of hemophilia-associated AIDS had been reported to the Centers for Disease Control through state health departments, hemophilia treatment centers (HTCs), and physicians. The total number of cases represents a cumulative incidence of 1.6 cases of AIDS per 100 hemophiliacs in the U.S. However, in 1985, 92% of persons with hemophilia A and 52% of those with hemophilia B in a U.S. hemophilia cohort had antibodies to human T-cell lymphotropic virus type IlI/lymphadenopathy-associated virus (HTLV-III/LAV). To determine the completeness of reporting of hemophiliac AIDS cases, a survey of HTCs, local National Hemophilia Foundation (NHF) chapters, and physicians known to have patients with hemophilia was conducted. From these sources, eight previously unreported cases of AIDS among hemophiliacs, including two from California (diagnosed in December 1984 and July 1985), two from Oregon (March 1986 and July 1985), and one each from Colorado (March 1985), Missouri (May 1985), New York (April 1985), and Virginia (January 1986), were discovered. In four instances the physicians assumed that the cases had been reported to the appropriate state health department, two cases involved physicians who did not realize their legal requirement to report AIDS cases to the state, one case involved a postmortem diagnosis of which the physician was unaware, and one case involved an acquired inhibitor to factor VIII which the physician did not realize constituted a case of AIDS. The Division of Host Factors (DHF), Center for Infectious Diseases, CDC, and the NHF surveyed all U.S. HTCs, local NHF chapters, and physicians known to have patients with hemophilia. On 14 May 1986, each HTC and physician was sent a list of persons with hemophilia- associated AIDS according to DHF records as of 1 May 1986. Cases were not identified by name but by date of birth, date of diagnosis, and nature of the AIDS diagnosis. The HTCs and physicians were asked to add to the list any other cases, confirmed or suspected. HTCs and physicians who had not responded by 1 August 1986 were telephoned by DHF personnel. Written responses were received from 61 (25%) of the HTCs and physicians contacted, while information was obtained by telephone from 213 of the addressees who had not responded. 1) Populations: Hemophiliacs (IA3), 2) Geographic Trends: U.S. (IB1) 1A3-Cen-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Jason, Janine, MD; Holman, Robert C., MD; Dixon, Gloria, RN; Lawrence, Dale N., MD; Bozeman, Lorna H., MS; Chorba, Terence L., MD; Tregillus, Leslie, MD; Evatt, Bruce L., MD; The Hemophilia/AIDS Collaborative Study Group. Effects of Exposure to Factor Concentrates Containing Donations From Identified AIDS Patients: A Matched Cohort Study. Journal of the American Medical Association, 3 October 1986, Vol. 256, No. 13: 1758-1762. Division of Host Factors, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. Since August 1983, four companies producing or distributing factor VIII or factor IX contentrate products have voluntarily withdrawn from distribution eight lots of concentrate for which one of the donors was later found to have developed AIDS. Because of the anxieties among hemophiliacs which have been raised by voluntary withdrawals, individuals exposed to these lots were tested for antibody and immune function. The prevalence of antibody to human immunodeficiency virus (HIV) was no higher among exposed recipients than among matched nonexposed recipients: 74.5% of exposed factor VIII recipients were seropositive, compared with 86.3% of the nonexposed recipients; 30.0% of exposed factor IX recipients were seropositive, compared with 40.0% of the nonexposed recipients. These results are not reassuring, as they support previous data showing a high prevalence of HIV antibody in people with hemophilia A in the U.S. On the other hand, they show that people exposed to lots of clotting factor that were later withdrawn were not more likely to develop antibody to HIV. In actuality, the withdrawn lots may not have differed from other lots in their content of HIV--both the "exposed" and "nonexposed" groups may in fact have been exposed to HIV to the extent that any effect of the specific withdrawn lots would not be detectable. The authors conclude that market withdrawals were not sufficient to limit the spread of AIDS among hemophiliacs, but that currently available methods of donor screening and inactivation of virus in blood products will prevent continued exposure within this population. This study compares hemophiliacs who were exposed to withdrawn concentrates with hemophiliacs who had not been exposed to the withdrawn lots. Matching was used for a subset of study subjects. All hemophiliacs in the distribution area of five withdrawn lots of factor VIII and three withdrawn lots of factor IX were contacted. These lots included blood components from one individual who developed AIDS 6 to 10 months after donation. The patients were first evaluated 12 to 19 months after factor distributions. For each subject, serum specimens were tested for antibody to HIV, and immunologic status was assessed. These cohorts will be followed up prospectively for up to 5 years. This report describes initial evaluation findings. The exposed group consisted of 119 hemophiliacs who had received blood products from exactly one withdrawn lot of factor VIII or factor IX 1A3-Jas-2 Policy Keys: clotting concentrate. The nonexposed group consisted of 95 hemophiliacs matched for age, type of factor received, sex, race, type of hemophilia, amount of factor received per year, and treatment center who had not received blood products from any of the withdrawn lots. Subjects in the exposed group were provided from 32 hemophilia treatment centers; nonexposed participants were provided from 43 centers. 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (1c) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Kreiss, Joan K., MD, MPH; Kitchen, Lynn W., MD; Prince, Harry E., PhD; Kasper, Carol K., MD; Goldstein, Allan L., PhD; Naylor, Paul H., PhD; Preble, Olivia, PhD; Stewart, John A., MD; Essex, Max, DVM, PhD. Human T Cell Leukemia Virus Type Ill Antibody, Lymphadenopathy, and Acquired Immune Deficiency Syndrome in Hemophiliac Subjects: Results of a Prospective Study. The American Journal of Medicine, March 1986, Vol. 80, No. 3: 345-350. Robert Wood Johnson Clinical Scholars Program, Wadsworth Veterans Administration Hospital, Cellular Immunology Laboratory, American Red Cross Blood Services, Hemophilia Center, Orthopaedic Hospital, and Department of Medicine, University of Southern California, Los Angeles, California; Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts; Department of Biochemistry, George Washington University School of Medicine, Washington, DC; Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, Maryland; Centers for Disease Control, Atlanta, Georgia. A cohort of 63 hemophiliac subjects was followed for clinical and immunologic abnormalities related to AIDS. When evaluated in early 1984, antibody to human T-cell lymphotropic virus type III (HTLV-II) was found in 59% of blood-clotting factor VIII or IX concentrate recipients, but in none of the cryoprecipitate or fresh-frozen plasma recipients. Seropositive subjects had been exposed to twice as much concentrate during the previous year as had seronegative subjects. The seropositive group had lower helper/suppressor T-cell ratios. By early 1984, 13 subjects had lymphadenopathy, and | had AIDS. Antibody to HTLV-III was detected in 13 of the l4 subjects with overt clinical disease. The prevalence of lymphadenopathy or AIDS among HTLV-III-seropositive subjects was 54%. The authors conclude that HTLV-II antibody occurs with high frequency in hemophiliac subjects and is related to the amount of factor VIII and [X infused. This was a prospective study of hemophiliacs, with clinical and immunologic observation on follow-up. Antibodies to HTLV-II were detected by direct membrane immunofluorescence. White blood cell counts, differentials, and T-cell subset determinations were performed. Tests were also performed to determine thymosin alpha-1 levels and beta-2-microglobulin levels, cytomegalovirus antibodies, and Epstein- Barr viral capsid antibodies. A cohort of 63 hemophiliacs were enrolled between November 1982 and March 1983 at a Los Angeles, California, hemophilia center. Of this group, 46 had hemophilia A, 12 had hemophilia B, and 5 had von Willebrand's disease. Thirty-seven had severe disease, 12 moderate, and 14 mild. Their ages ranged from 19 to 67 years (mean, 36). No homosexuals were included, and only one admitted to infrequent intravenous drug abuse, denying sharing needles or syringes. Fifty-one 1A3-Kre-3 Policy Keys: patients received factor VIII or IX clotting factor concentrate, and 12 received cryoprecipitate and/or fresh-frozen plasma. Factor recipients used an average of 122,000 factor units per year; plasma recipients used an average of 37 bags annually. The control group consisted of 100 age-matched Los Angeles blood donors. 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (IIC) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Ragni, Margaret V.; Tegtmeier, Gary E.; Levy, Jay A.; Kaminsky, Lawrence S.; Lewis, Jessica H.; Spero, Joel A.; Bontempo, Franklin A.; Handwerk-Leber, Cindy; Bayer, William L.; Zimmerman, Daniel H.; Britz, Judith A. AIDS Retrovirus Antibodies in Hemophiliacs Treated with Factor VIII or Factor IX Concentrates, Cryoprecipitate, or Fresh Frozen Plasma: Prevalence, Seroconversion Rate, and Clinical Correlations. Blood, March 1986, Vol. 67, No. 3: 592-595. Department of Medicine, University of Pittsburgh and Central Blood Bank of Pittsburgh, Pittsburgh, Pennsylvania; Community Blood Center of Greater Kansas, Kansas City, Missouri; Cancer Research Institute, Department of Medicine, University of California School of Medicine, San Francisco; and Electronucleonics, Inc., Columbia, Maryland. This study was conducted to estimate the prevalence of human T-cell lymphotropic virus type III (HTLV-II) among hemophiliacs and the rate of conversion to HTLV-II positive blood tests. Antibodies to the AIDS retrovirus (HTLV-II) were detected with increasing prevalence in a population of western Pennsylvania hemophiliacs between 1981 and 1984. Of the sample, 7.7% had positive blood tests for antibodies to HTLV-II in 1981, 20% in 1982, 45.5% in 1983, and 62.5% in 1984. The seropositive patients included three-fourths of those receiving clotting factor VIII concentrate, one-third of those receiving factor IX concentrate, one-fifth of those receiving cryoprecipitate, and none of those receiving fresh frozen plasma. The rate of HTLV-IIl seroconversion, determined for #43 seropositive hemophiliacs from this group who were sampled over time, was 0% in 1977, 4.7% in 1978, 4.9% in 1979, 2.6% in 1980, 10.5% in 1981, 52.9% in 1982, 87.5% in 1983, and 100% in 1984. Of 27 who were seropositive for more than 3 years, 4 developed AIDS, and 7 developed AIDS-related complex (ARC). Of 16 hemophiliacs who were seropositive for less than 3 years, none has developed AIDS and 3 have developed ARC. The mean time from seroconversion to onset of ARC was 0.8 years, plus or minus 0.2 years. This longitudinal seroepidemiological study involved long-term testing for antibodies to HTLV-III in a hemophiliac population. Only the first available blood sample, beginning in 1984 and going back to 1981, was studied. A subset of 43 seropositive persons for whom annual or biannual blood samples between 1977 and 1984 were available were used to study the rate of seroconversion. Antibodies to HTLV-II were measured by enzyme-linked immunosorbent assay performed on blood sera frozen for several months to 6 years; samples with an optical density of greater than 0.100 in two separate assays were considered positive. A total of 190 hemophiliacs from western Pennsylvania receiving blood product therapy were studied. Of this group, 155 had hemophilia A; 82 of them were treated with factor VIII concentrate, 59 were treated with cyroprecipitate, and 14 were treated with factor IX concentrate. The 35 1A3-Rag-4 Policy Keys: persons with hemophilia B included 16 treated with factor [X concentrate and 19 treated with fresh-frozen plasma. Demographic characteristics of the group are not presented, but the subset of 43 persons examined for date of seroconversion did not differ from the group of 190 in age, race, or blood product use. 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (IIC), 3) Incubation Period and Disease Stages (IIIC) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Daniel, V.; Opelz, G.; Schafer, A.; Schimpf, Kl.; Wendler, [.; Hunsmann, G. Correlation of Immune Defects in Hemophilia with HTLV-II Antibody Titers. Vox Sanguinis, 1986, Vol. 51: 35-39. Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg (Daniel, Opelz, Schafer); Rehabilitation Hospital and Hemophilia Center, Rehabilitation Foundation, Heidelberg (Schimpf); German Primate Center, Gottingen, Federal Republic of Germany (Wendler, Hunsmann). Hemophilia patients were tested to see whether abnormal immunological status and human T-cell lymphotropic virus type III (HTLV-II) antibody levels may be correlated. Of 170 hemophiliacs tested, 83 (49%) were seronegative for HTLV-III antibodies, 50 (29%) were seropositive, and 37 (22%) were strongly seropositive. In contrast, 2 of 226 renal dialysis patients and none of 45 healthy controls were HTLV-II antibody positive. A subset of 48 hemophilia patients was screened repeatedly during a 2-year period. Twenty-one were initially seropositive, and another 16 converted during the study. Markedly decreased (<0.5) or moderately decreased (<1.0) helper/suppressor T-cell ratios were found in 86% of patients with high levels of HTLV-III antibody, in 65% of patients with low levels, and in 35% of patients who were antibody negative. A similar correlation between level of HTLV-III antibodies and decreased in vitro response of lymphocytes to pokeweed mitogens was also found: only 20% of seronegative hemophiliacs showed a deficient response, compared with 46% and 50% of low- and high-antibody-level patients, respectively. Similar correlations with HTLV-II antibody level were found for elevated serum neopterin and serum immunoglobulin G. However, there was no correlation of HLA-DR5 with the development of HTLV-II antibody. Only 3% of seronegative patients were abnormal in all four immunologic tests, compared with 25% of those with low antibody levels and 36% of those with high antibody levels. During a 2-year period, hemophilia patients, renal dialysis patients, and healthy controls were studied. Immunological tests were performed and correlated with results from HTLV-III antibody assays. T-cell subsets were determined with OKT4 and OKT8 monoclonal antibodies. Mitogen responsiveness tests were performed by standard methods. Serum neopterin was also measured, and immunoglobulin G antibodies to HTLV- [II were determined by enzyme-linked immunosorbent assay. Positive and questionable results were confirmed by immunoprecipitation. The study included 170 hemophilia patients, 226 renal dialysis patients, and 45 healthy controls from the Federal Republic of Germany. Of the hemophilia patients, 136 had hemophilia A, 23 had hemophilia B, 7 had Willebrand's disease, | had factor V deficiency, 2 had factor VII ceficiency, and | had factor VIII deficiency. All patients were cared for at the Heidelberg Hemophilia Center. During the course of the study, two patients were diagnosed with AIDS. An additional patient who died 1A3-Dan-5 of Pneumocystis carinii pneumonia during the study was suspected of having AIDS. Policy Keys: 1) Populations: Hemophiliacs (IA3), 2) Geographic Trends: Europe (West Germany) (IB4), 3) Immunological Aspects (IIE), 4) Transmission: Blood Products (IIC) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kitchen, L.; Leal, M.; Wichmann, [.; Lissen, E.; Ollero, M.; Allan, J.S.; McLane, M.F.; and Essex, M. Antibodies to Human T-Cell Leukemia Virus Type III In Hemophiliacs from Spain. Blood, December 1985, Vol. 66, No. 6: 1473-1475. Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts; Departments of Internal Medicine and Immunology, Hospital General Ciudad Sanitaria Virgen del Rocio, Sevilla, Spain. Blood serum samples from 50 Sevilla, Spain, hemophiliacs and 20 healthy Spanish volunteer blood bank donors were tested for antibody to human T-cell lymphotropic virus type III (HTLV-II). At serum collection, 42 hemophiliacs were asymptomatic, | had clinical AIDS, and 7 had lymphadenopathy. Of 50 hemophiliac blood samples tested, 34 (68%) reacted with the HTLV-IlI-infected cells by indirect membrane immunofluorescence, but not with uninfected H9 cells. All 34 also tested positive by radioimmunoprecipitation. Serum samples from the 20 healthy blood bank donors were all negative by both assays. Of the 48 hemophilia A patients tested, 28 (68%) were positive for antibodies; of the nine hemophilia B patients tested, six (66%) were positive. The one hemophilia B patient who had never been transfused was negative for antibody by both methods. All but one of the eight patients with AIDS or lymphadendopathy tested positive, and all were hemophilia A patients. The seropositivity rate among Spanish hemophiliacs is similar to that of American hemophiliacs, possibly due to the use in Spain of U.S. commercial clotting-factor concentrates. The authors conclude that exposure to HTLV-III is widespread among asymptomatic hemophiliacs in Spain. This study compared the HTLV-II antibody response in hemophiliacs with that in volunteer blood bank donors. Serum samples were initially examined at 1:4 dilution by indirect membrane immunofluorescence on an HTLV-Ill-infected cell line (H9/HTLV-III) and an uninfected cell line (H9). Samples were then tested by radioimmunoprecipitation. A total of 50 hemophiliacs (average age, 18.8 years) from the Hospital General Ciudad Sanitaria Virgen del Rocio in Sevilla, Spain, and 20 healthy Spanish volunteer blood bank donors were studied. Of the 50 hemophiliacs, 49 had received commercial clotting factors from the U.S., and one had never been transfused; 41 were hemophilia A, and 9 were hemophilia B; | had clinical AIDS, and 7 had lymphadenopathy. 1) Populations: Hemophiliacs (IA3), 2) Geographic Trends: Europe (Spain) (IB4), 3) Transmission: Blood Products (IIC) 1A3-Kit-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Jones, Peter; Hamilton, P.J.; Bird, Graham; Fearns, Maureen; Oxley, Alan; Tedder, Richard; Cheingsong-Popov, Rachanee; Codd, Arthur. AIDS and Haemophilia: Morbidity and Mortality in a Well Defined Population. British Medical Journal, 14 September 1985, Vol. 291, No. 6497: 695-699. Newcastle Haemophilia Reference Centre and Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne (Jones, Hamilton, Fearns, Oxley); Department of Immunology, Newcastle General Hospital, Newcastle upon Tyne (Bird); Virology Section, Department of Microbiology, Middlesex Hospital and University College Medical School, London (Tedder); Institute of Cancer Research, Chester Beatty Laboratories, London (Cheingsong-Popov); Public Health Laboratory Service, Newcastle General Hospital, Newcastle upon Tyne, England (Codd). Patients in the United Kingdom who had hereditary blood disorders and had received multiple blood transfusions were examined for evidence of AIDS. Of 99 patients with severe hemophilia type A who were tested, 76 (77%) were found to be positive for antibodies to human T-cell lymphotropic virus type III (HTLV-II). All but one of these seropositive patients had received commercial blood-clotting factor VIII concentrate at some time in the past. Of 18 patients with hemophilia type B who were tested, all were seronegative. These patients had been exposed only to National Health Service (NHS) factor IX concentrate from volunteer donors. Three of 36 (8%) heterosexual partners of patients were also positive for antibodies to HTLV-III. One, who had recently received blood transfusions as well, had AIDS. Three patients with severe hemophilia A died from AIDS. A further 30 hemophiliacs had AIDS-related complex or lymphadenopathy that could be related to HTLV-II infection. No evidence of casual spread of AIDS was found, since all 68 health care staff were negative for HTLV-II, including three surgeons who regularly worked with patients who tested positive for HTLV-IIL. This was a follow-up study that used case reports of hemophiliac patients and testing for HTLV-II], initially by competitive radioimmunoassay and, since 1985, by enzyme-linked immunosorbent assay (ELISA). Follow-up included repeated clinical examination and musculoskeletal assessment, monitoring of blood counts (hemoglobin, white cell, and platelet), liver function tests, urine analysis, x-rays, and referral to specialists as indicated. A total of 143 patients with multiple blood product transfusions and hereditary blood disorders were studied at Newcastle upon Tyne, England. Of this group, 95 had received multidonor clotting factor VIII concentrate from both the NHS volunteer-donor panel and commercial sources. The remainder had received only factor VIII concentrate from one source or the other or had received factor IX concentrate from NHS volunteer-donor panel. Of the 143, a subset of 120 were tested for 1A3-Jon-7 antibody to HTLV-II, along with 36 sexual partners of those with hemophilia A and 68 centre staff members. Policy Keys: 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (IIC), 3) Geographic Trends: Europe (U.K.) (IB4) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jason, Janine, MD; McDougal, J. Steven, MD; Holman, Robert C., MS; Stein, Sidney F., MD; Lawrence, Dale N., MD; Nicholson, Janet K.A., PhD; Dixon, Gloria, RN; Doxey, Melton; Evatt, Bruce L., MD. Human T-Lymphotropic Retrovirus Type IlI/Lymphadenopathy-Associ- ated Virus Antibody: Association with Hemophiliacs' Immune Status and Blood Component Usage. Journal of the American Medical Association, 21 June 1985, Vol. 253, No. 23: 3409-3415. Division of Host Factors, Center for Infectious Diseases, Centers for Disease Control, Atlanta (Jason, McDougal, Lawrence, Nicholson, Evatt, Holman, Dixon, Doxey); Department of Medicine, Emory University School of Medicine, Atlanta, Georgia (Stein). Various groups of hemophiliacs were tested for presence of antibodies to human T-cell lymphotropic virus type IlI/lymphadenopathy-associated virus (HTLV-III/LAV). The groups were evaluated, and the prevalence of antibodies to the virus in blood was compared among groups receiving different types of blood products. Of the hemophiliacs tested, those who received blood-clotting factor VIII concentrate had the highest rate (74%) of blood test positivity to HTLV-III/LAV; factor IX concentrate recipients had a significantly higher rate (39%) than both recipients of frozen packed red blood cells (4%) and persons not transfused (4%). In recipients of factor VIII concentrate, HTLV-III/LAV seropositivity was significantly associated with more severe hemophilia, greater factor dosages, elevated immunoglobulin and immune complex levels, lower numbers of helper T cells, and lower helper/suppressor T-cell ratios. In factor IX recipients, seropositivity was associated with more severe hemophilia. The authors conclude that because the extent to which recipients of pooled blood products are vulnerable to new infection appears to be striking, both factor VIII and factor IX concentrates may transmit HTLV-III/LAV. Factor IX recipients in particular may benefit from AIDS prevention techniques involving use of heat-treated blood products. Blood specimens were tested for the presence of antibody to HTLV- [II/LAV by Western blot analyses. In U.S. subjects, lymphocyte subpopulations were quantitated by indirect immunofluorescence. Immunoglobulins G, A, and M were quantitated. The test results were compared by clinic location, type of blood product and treatment received, and severity of hemophilia. A total of 386 healthy subjects were studied, including 234 recipients of clotting factor VIII, 36 recipients of clotting factor IX, 69 long-term recipients of frozen packed red blood cells, and 47 not receiving routine transfusion therapy. Hemophiliac and other subjects were drawn from clinics in New York City, Georgia, elsewhere in the U.S., and Vienna, Austria. All but one of the participants was male; 94% were white. 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (IIC), 3) Blood Product Safety: Inactivation of Virus (VB3) 1A3-Jas-8 Author(s): Title: Source: Institution: Findings: Method: Sample: Ball, S.E., MA, MRCP; Hows, J.M., MD, MRCPATH; Worsley, A.M., MB, MRCP; Luzzatto, L., MD, FRCP; Chu, A.C., MB, MRCP; Meacham, R.; Morris, J.; Cheingsong-Popov, R., MSC, PhD; Weiss, R.A., PhD; Tedder, R., MB, MRCPATH. Seroconversion of Human T Cell Lymphotropic Virus III (HTLV-II) in Patients with Haemophilia: a Longitudinal Study. British Medical Journal, 8 June 1985, Vol. 290: 1705-1706. Department of Haematology, (Ball, Hows, Worsley, Luzzatto) and Dermatology Unit (Chu, Meacham, Morris), Royal Postgraduate Medical School, London, England; Institute of Cancer Research, Chester Beatty Laboratories, London, England (Cheingsong-Popov, Weiss); Department of Virology, Middlesex Hospital Medical School, London, England (Tedder). This longitudinal study, part of a surveillance program on AIDS, tested British hemophiliac patients for clinical and immunologic features associated with AIDS. Testing on stored patient blood sera obtained between 1979 and 1984 revealed that 20 of 30 patients had detectable antibodies to human T-cell lymphotropic virus type III (HTLV-III) in 1984, with the earliest positive result detected in January 1981. Approxi- mately 15% of the patients seroconverted each year until 1984. Serocon- version could usually be dated to within 6 months of antibody detection, but no coincidental illness could be identified. No patients with detectable antibody later became seronegative. Of five patients found to have splenomegaly or lymphadenopathy, all were seropositive. Most seropositive patients had had large amounts of factor VIII concentrate treatment, predominantly commercial concentrate from the U.S. However, four patients who seroconverted during 1984 had had little treatment, although all concentrate was from the U.S. Five patients who were seronegative had used only products from the British National Health Service over the last 5 years; this is in keeping with the low positivity rate for antibodies to HTLV-III in British donors. The authors caution that the meaning of patients' positive antibody status is unclear. For example, of four patients who were seropositive for 4 years, three had normal helper T-cell counts and would probably not develop AIDS, whereas only one had recently detected lymphadenopathy and splenomegaly. Relative values for helper and suppressor T cells were determined by immunofluorescence with monoclonal antibodies OKT4 and OKT&8. Abso- lute values were calculated from a count of total lymphocytes on the same day. Stored sera obtained between 1979 and 1984 were tested for HTLV-III antibodies by radioimmunoassay. Thirty British hemophiliac patients with hemophilia A who had been treated for postoperative bleeding) who had received factor VIII concen- trate between 1979 and 1984 were studied. One of the men had been tattooed over the last 10 years. No other AIDS risk factors were involved. 1A3-Bal-9 Policy Keys: 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (IIC), 3) Incubation Period and Disease Stages (IIIC) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Lederman, Michael M., MD; Ratnoff, Oscar D., MD; Evatt, Bruce L., MD; McDougal, J. Steven, MD. Acquisition of Antibody to Lymphadenopathy-Associated Virus in Patients with Classic Hemophilia (Factor VIII Deficiency). Annals of Internal Medicine, June 1985, Vol. 102, No. 6: 753-757. Department of Medicine, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio; Centers for Disease Control, Atlanta, Georgia. This study was conducted to observe retrospectively the prevalence of lymphadenopathy-associated virus (LAV) antibodies in hemophiliacs. Antibody to LAV was assayed in 461 blood serum and plasma samples that had been collected from 149 patients with classic hemophilia and 64 controls and stored for as long as 18 years. No control or patient samples obtained before 1980 contained antibody to this retrovirus. The prevalence of antibody to LAV in the hemophiliac patient samples rose from 15% (2 of 13) in 1980 to 62% (18 of 29) in 1984. During this time, none of eight untreated hemophiliacs and none of 26 hemophiliacs treated solely with cryoprecipitates (frozen plasma precipitates) had antibody to LAV. In contrast, the prevalence of antibody to LAV among hemophiliacs treated with freeze-dried clotting factor rose from 25% (2 of 8) in 1980 to 78% (18 of 23) in 1984. Hemophiliacs testing positive for LAV antibody had fewer helper T cells and lower proliferative responses to mitogen than similarly treated hemophiliacs without LAV antibody. Samples obtained from hemophiliacs and control subjects over an 18-year period were blindly tested for LAV antibody by enzyme-linked immuno- sorbent assay, with Western blot confirmation of borderline results. Serological studies of T-cell subpopulations were also conducted, and natural killer cell activity was assayed. Samples were obtained from 149 factor VIII-deficient hemophiliacs and from 64 healthy laboratory workers at Case Western Reserve University (Cleveland, Ohio). A total of 461 coded blood serum and plasma samples were tested. 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (IIC) 1A3-Led-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Evatt, Bruce L., MD; Gomperts, Edward D., MD; McDougal, J. Steven, MD; Ramsey, Rosemary, B., MS. Coincidental Appearance of LAV/HTLV-III Antibodies in Hemophiliacs and the Onset of the AIDS Epidemic. The New England Journal of Medicine, 21 February 1985, Vol. 312, No. 8: 483-485. Division of Host Factors, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; Children's Hospital of Los Angeles, Los Angeles, California. Blood serum samples that had been collected in 1968 and 1969 and between 1978 and 1984 were tested for antibody to lymphadenopathy- associated virus (LAV; also known as human T-cell lymphotropic virus type III). Antibody to LAV was not detected in the serum of the 1968 and 1969 samples of patients with mild hemophilia A. Before 1980 LAV was present in only 1 of 21 patients with hemophilia A in California. Among most of the 21 patients, antibody was not detected until 1982, and the percent positive increased rapidly in 1983. By 1984, more than 85% of the group had antibody to LAV. Blood serum samples from Georgia patients with hemophilia A, who as a group had more severe hemophilia and had received more clotting-factor concentrates than average, indicated that 8 of 14 had antibody in 1981, while 8 of 8 had antibody in 1984. The trend in both California and Georgia was toward increased prevalence of antibody from 1981 to 1984. The extent of LAV antibody positivity among patients with hemophilia B was not as great as among those with hemophilia A. None of the patients have contracted AIDS. Of 22 patients receiving clotting factor VIII concentrates, 7 have had mild lymphadenopathy. Low helper/suppressor T-cell ratios, reflecting patients’ immune status, were found in 7 of 14 patients studied. All patients without antibody to LAV were free of lymphadenopathy and immune system abnormalities. Blood serum samples were tested for the presence of antibody to LAV by a Western blot technique. T-cell subpopulations were quantitated by indirect immunofluorescence with Leul, Leu2, Leu3, Leu4, and Leu) antibodies. Samples from 1968 and 1969 were from 15 persons with mild hemophilia A in New York, California, and Texas. Clinical histories of these patients were not available. California samples were collected between 1978 and 1984 from 21 patients with hemophilia A, 6 with hemophilia B, I with Willebrand's disease, and | with factor VII deficiency. All these patients had been enrolled in a hemophilia comprehensive-care program at Children's Hospital of Los Angeles, and clinical histories were available. In addition, blood serum samples from patients with hemophilia A in Georgia were tested, 14 collected in 1981 and 8 in 1984. These patients had severe hemophilia A and were treated with factor VIII concentrates. 1A3-Eva-11 Policy Keys: 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (IIC), 3) Geographic Trends: U.S. (IB1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Daly, Helena M.; Palmer, R.; Scott, G.L.; Lee, G. AIDS Surveillance in Haemophilia. British Journal of Haematology, 1985, Vol. 59: 383-390. Departments of Haematology, Bristol Royal Infirmary and Southmead Hospital, Bristol, England. After a hemophilia patient died of Pneumocystis carinii pneumonia, immunologic evaluations of 43 other clinic patients being treated for hemophilia and Von Willebrand's disease were conducted to detect any immunologic abnormalities resulting from receipt of clotting-factor concentrates. None of the patients admitted to being homosexual or to intravenous drug abuse. No patient was anemic or had symptomatic liver disease. Three of 43 patients showed weight loss or other clinical features of prodromal AIDS. Nine patients (21%) were seropositive for cytomegalovirus, a normal percentage for a general population. Of the patients tested, 76% showed increase in level of one or more immunoglobulins, 12% showing increase in all three classes and 19% in two classes. Eleven (25%) of the patients had lowered lymphocyte counts, ten patients consistently so on repeated testing. Six of these eleven had absolute T-cell depletion due to a reduction of helper T cells; the other five were presumed to have reduced numbers of B cells. Abnormal values were found for 31 (71%) of the 43 patients. Most of the observed immunologic abnormalities in this population are thought to be a response to repeated exposure to foreign proteins through clotting- factor concentrate used in treatment of hemophilia, and the authors think only profound abnormalities due to helper cell depletion, rare in asymptomatic patients, are significant. The following routine blood tests were performed: full blood count, differential white cell count, direct Coombs test, serum immunoglob- ulins, beta 2 microglobulin, bilirubin, alkaline phosphatase, aspartate transaminase, gamma glutamyl transferase, hepatitis B virus surface antigen and antibody, hepatitis B virus e antigen and antibody, and cytomegalovirus titers. T-cell subsets were determined by using mono- clonal antibodies and fluorescence microscopy. Tests on healthy volun- teer blood donors and laboratory staff were used to establish the normal range for these T-cell subsets. A total of 43 British hemophiliacs (35 males, 8 females) receiving clinic treatment were studied; ages ranged from 13 to 78 (mean, 35). Fifty healthy volunteer blood donors and 11 laboratory staff served as controls. 1) Populations: Hemophiliacs (IA3), 2) Immunological Aspects (IlIE), 3) Transmission: Blood Products (IIC) 1A3-Dal-12 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Johnson, Robert E.; Lawrence, Dale N.; Evatt, Bruce L.; Bregman, Dennis J.; Zyla, Lawrence D.; Curran, James W.; Aledort, Louis M.; Eyster, M. Elaine; Brownstein, Alan P.; Carman, Charles J. Acquired Immunodeficiency Syndrome Among Patients Attending Hemophilia Treatment Centers and Mortality Experience of Hemo- philiacs in the United States. American Journal of Epidemiology, 1985, Vol. 121, No. 6: 797-810. Centers for Disease Control, Atlanta, Georgia (Johnson, Lawrence, Evatt, Bregman, Zyla, Curran); National Hemophilia Foundation, New York City, New York (Aledort, Eyster, Brownstein, Carman). The purpose of this study was to determine the onset and incidence of AIDS among hemophiliacs and to determine trends in hemophilia mortality since the introduction of clotting-factor concentrates in the late 1960s. Hemophilia treatment centers were monitored for AIDS cases through June 1984; nine deaths (17.3% of deaths from all causes) were noted in the 1978-82 period. A dramatic reduction was found in hemophilia mortality rates in the 1970s, due to improved care and the availability of clotting-factor concentrates. The first AIDS case was reported in 1981; incidence of AIDS among the factor VIII-deficient and factor [X-deficient patients remained at 0.6 cases per 1,000 clinic attendees through 1983 but increased sharply to 5.4 cases per 1,000 in the first quarter of 1984. Thus, AIDS is a new and important cause of illness and mortality among hemophiliacs. The AIDS patients who attended hemophilia clinics were distributed all over the U.S., and they were older than those without AIDS. The AIDS cases were also associated with more frequent use of freeze-dried clotting-factor concentrate. A direct mail survey of 116 hemophilia treatment centers in the 48 contiguous states was conducted; responses were received from 98 (84%). Questionnaires asked for reports of deaths from any cause of patients seen in 1978 and reports of all AIDS-like illnesses of hemophil- lacs seen between | October 1981 and 30 September 1983. Death reports from the National Center for Health Statistics Vital Statistics Program and from the hemophilia treatment center survey provided mortality trends for 1968-79 and for 1978-82, respectively. A total of 6,717 hemophiliacs (46% of the known U.S. total) were reported as hemophiliac treatment center patients. Their median age was about 19 years. 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (IC). 1A3-Joh-13 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Bloom, A.L. Acquired Immunodeficiency Syndrome and Other Possible Immunological Disorders in European Haemophilacs. The Lancet, 30 June 1984, Vol. 1, No. 8392: 1452-1455. Department of Haematology, Welsh National School of Medicine, Cardiff, Wales, United Kingdom. European hemophilia centers replied to a questionnaire covering 13,147 patients with hemophilia or Willebrand's disease who were treated with blood products. Eight cases of AIDS were identified, as well as three patients with lymphoma. In addition, 179 cases of other possible immunological disorders were recorded, including 86 with lymphadeno- pathy, but 70 of these occurred at one center. None of the abnormalities could be related to use of any particular type of clotting-factor VIII concentrates. Forty centers admitted to a recent change of clinical practice, such as stopping or reducing the use of U.S. blood products, but about two-thirds had made no changes. A simple questionnaire was sent to the directors of 20! European hemophilia centers listed in the World Federation of Hemophilia Guide for Travelling Hemophiliacs. The questionnaires were dispatched in early December 1983, and responses were received by 20 January 1984. The information solicited concerned the number of patients at risk, the types of treatment used, recent changes in treatment policy, and the number and details of patients with AIDS and possible AIDS-related features. The report covers an estimated 65% of treated hemophiliacs in 18 European countries. Replies were received from 135 of the 201 European hemophilia centers surveyed. These covered 8,928 patients with hemophilia A, 1,889 with hemophilia B, and 2,330 with Willebrand's disease treated with blood products. 1) Populations: Hemophiliacs (IA3), 2) Transmission: Blood Products (IC), 3) Information/Education: Risk Behaviors and Protection (Hemophiliacs) (VA2) 1A3-Blo-14 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Allain, J.P. SIDA, Syndromes Apparentes et Hemophilie: Situation en France et Etudes en Cours. Revue Francaise de Transfusion et Immuno-hematologie, 1984, Vol. 27, No. 4: 459-461. Centre National de Transfusion Sanguine, Paris, France. This study reports the occurrence of AIDS and AIDS-related disorders in patients at 25 hemophilia centers in France. Among 2,388 hemophiliacs, representing approximately 60% of all hemophiliacs in France, no case of AIDS was found. Four patients had lymphadenopathy. Of 37 patients tested for immune status, l4 showed below-normal values, reporting helper /suppressor T-cell ratios below 1. In May 1983, a mail survey was sent to 25 hemophilia centers in France to obtain information about the occurrence of AIDS and AIDS-related disorders. Thirty-seven patients were tested for T-lymphocyte populations to assess their immune status. A total of 2,388 hemophiliacs in 25 hemophilia centers in France were reported on in this survey. 1) Populations: Hemophiliacs (IA3), 2) Geographic Trends: Europe (France) (IB4), 3) Immunological Aspects (IIE) 1A3-A11-15 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Green, D. AIDS and Immunologic Abnormalities in European and American Hemophiliacs. Scandinavian Journal of Haematology, 1984, Suppl. 40, Vol. 33: 367-369. Atherosclerosis Program, Department of Medicine, Northwestern University Medical School and Rehabilitation Institute of Chicago, Chicago, Illinois. This study reports results from a survey of European hemophilia centers to determine the frequency of AIDS and other immunity disorders in their patient popuiations. Data representing 4,310 patients in 15 countries were obtained. Therapeutic clotting-factor concentrates of local and commercial origin had been in use in these centers for an average of 12 years. Only five possible cases of AIDS were identified, and a few of these did not meet the strictly defined U.S. Centers for Disease Control (CDC) criteria for AIDS. All of these patients had lymphadenopathy, and most experienced fever and weight loss. None had Pneumocystis carinii infection, which is characteristic of a majority of AIDS cases in the U.S. The author concludes that while disturbances of immunoregulation are common in hemophiliacs, to date classical AIDS has appeared infrequently. All identifiable European hemophilia centers were systematically surveyed, using a questionnaire which included queries about the types of therapeutic concentrates used for the treatment of severe factor VIII- and factor IX-deficient hemophiliacs and the duration that such concentrates had been in use. Centers were asked to identify any hemophiliac with cellular immune dysfunction. Replies were received from 20 centers in 15 countries, representing 4,310 hemophiliac subjects. 1) Populations: Hemophiliacs (IA3), 2) Geographic Trends: Europe (IB4), 3) Transmission: Blood Products (IIC) 1A3-Gre-16 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: deShazo, Richard D., MD; Andes, W. Abe, MD; Nordberg, Judy, BA; Newton, Julie, BS; Daul, Carolyn, MD, PhD; Bozelka, Brian, PhD. An Immunologic Evaluation of Hemophiliac Patients and Their Wives: Relationships to the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, August 1983, Vol. 99, No. 2: 159-164. Sections of Clinical Immunology and Hematology-Oncology, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana. In an 8-month prospective study of apparently healthy hemophiliacs with factor VIII deficiency and factor [IX deficiency, both groups showed depressed helper/suppressor T-cell ratios, the result of decreased percentage and number of helper (T4) lymphocytes and increased percentage of suppressor (T8) lymphocytes. Abnormalities in T- lymphocyte counts were most severe In seven patients with factor VIII deficiency who developed lymphadenopathy. No correlation was found between helper/suppressor ratios or lymphocyte responses to mitogen and the amount of factor VIII concentrate used per year. No significant association was found between amount of clotting factor concentrate administered and immunologic status. Wives of factor VIlI-deficient patients showed decreased percentages of T4 cells, but had normal lymphocyte responses to mitogen. The authors think it unlikely that these immunologic abnormalities are intrinsic to hemophilia. They recommend careful medical surveillance of hemophiliac recipients of these blood products who demonstrate lymph node swelling. Immunologic evaluations were done on samples of centrifuged whole blood, using monoclonal antibodies; studies were done by direct immunofluorescence, each test analyzing 25,000 cells. Serologic studies were done by enzyme-linked immunosorbent assay with commercial reagents. Healthy patients at a New Orleans hemophilia clinic were studied over an 8-month period, 24 of them with classic hemophilia (factor VIII deficiency) and 5 with factor IX deficiency. Their ages ranged from 10 to 66 years. No patient was homosexual, abused IV drugs, or had recent illness. Seventeen healthy male laboratory workers served as controls. Five apparently healthy wives and active sexual partners of asympto- matic factor VIII-deficient patients with lowered helper/suppressor ratios were also studied; a group of age-matched women served as controls. 1) Populations: Hemophiliacs (IA3), 2) Immunological Aspects (IIE), 3) Transmission: Blood Products (IIC), 4) Populations: Heterosexuals (IA6) 1A3-deS-17 [. Prevalence and Spread of AIDS/HTLV-III/LAV A. Population Studies and Groups at Risk 4, Pediatric Cases Author(s): Title: Source: Institution: Findings: Mann, Jonathan M.; Davachi, Farzin; Quinn, Thomas C.; Bosenge, Ngaly; Piot, Peter; Asila, Pangu Kaza; Francis, Henry; Baudoux, Paola; Nzilambi, Nzila; Colebunders, Robert L.; Kabote, Ndoko; Malonga, Miatudilaj Curran, James W. Risk Factors for Human Immunodeficiency Virus Seropositivity Among Children 1-24 Months Old in Kinshasa, Zaire. The Lancet, 20 September 1986, Vol. 2, No. 8508: 654-656. Projet SIDA, Department of Public Health, Kinshasa, Zaire (Mann, Bosenge, Francis, Nzilambi); AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Mann, Curran); Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (Quinn, Francis); Department of Pediatrics, Mama Yemo Hospital, Kinshasa, Zaire (Davachi, Baudoux, Kabote); Institute of Tropical Medicine, Antwerp, Belgium (Piot, Colebunders); Department of Public Health, Kinshasa, Zaire (Asila, Malonga). The prevalence of antibody to human immunodeficiency virus (HIV) was determined in Kinshasa, Zaire, among infants in the hospital and attending a well-child clinic and their mothers. Of 258 hospital children, 32 (12%) were HIV antibody seropositive, compared with 12 of 191 (6%) clinic children. Twenty of 258 (8%) mothers of hospital children and 16 of 191 (8%) clinic mothers were seropositive. Maternal HIV seropositivity was the major risk factor for child seropositivity in this study, as in the U.S. and Europe, implying transmission from mother to child. For children of seronegative mothers, medical injections seemed to be the most important risk factor, followed by previous blood transfusion or hospital admission. Seropositive children of seropositive mothers received fewer injections than did those of seronegative mothers. However, childhood vaccination was not associated with HIV seropositivity. Injections are often administered in dispensaries which reuse needles and syringes yet may not adequately sterilize the equipment. Further, injections are frequently given by untrained personnel or traditional healers. Blood transfusions may also be an important mode of HIV transmission, as suggested by the 6.3% prevalence of seropositivity documented in a survey of blood donors at a Kinshasa hospital in 1984. All but 1 of the 16 seropositive hospital children with seronegative mothers were boys, compared with 6 of 16 children with seropositive mothers. Predominance in males has also been noted among transfusion-associated AIDS cases in the U.S. These paral- lel observations may suggest that male infants and children may be more susceptible to HIV infection after parenteral exposure. HIV disease is difficult to recognize in Kinshasa children for several reasons--the clinical manifestations are not specific to HIV infection because of a relatively high incidence of gastrointestinal disease, pulmonary disease, malnutrition, and anemia among seronegative children; limited ability to exclude primary immunodeficiencies or confirm opportunistic infections through laboratory tests; and the lack of a distinct high-risk profile associated with maternal or pediatric HIV 1A4-Man-1 Method: Sample Size: Policy Keys: infection. Earlier estimates of the incidence of pediatric AIDS may have been much too low. The infants and their mothers were tested for antibody to HIV by an enzyme-linked immunosorbent assay and by Western blot analysis. A pediatrician interviewed consenting parents, reviewed hospital charts, and did the venipunctures on mothers and children. A total of 258 hospital and 191 clinic children and their mothers were enrolled in the study. Candidates for study included children 2 years of age and younger admitted to the general pediatrics or measles wards of Mama Yemo Hospital in Kinshasa, Zaire, from 4 June to 23 August 1985, as well as the first 10 to 15 children daily attending the well-child clinic at the hospital from 19 August to 18 September 1985. 1) Populations: Pediatric Cases (IA%4), 2) Geographic Trends: Africa (Zaire) (IB5), 3) Transmission: Blood Transfusion (IIC), 4) Transmission: Medical Injections (IIG), 5) Transmission: Perinatal (IID) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lauzon, Dominique, MD; Delage, Gilles, MD; Brochu, Pierre, MD; Michaud, Jean, MD; Jasmin, Gaetan, MD; Joncas, Jean H., MD; Lapointe, Normand, MD. Pathogens in Children with Severe Combined Immune Deficiency Disease or AIDS. Canadian Medical Association Journal, 1 July 1986, Vol. 135: 33-38. Departments of Microbiology and Immunology, Pathology and Pediatrics, Hopital Sainte-Justine, Montreal; Universite de Montreal, Canada. This comparative study evaluated the frequency and severity of illnesses caused by various microbial pathogens in 15 children with severe combined immune deficiency disease (SCID) and eight children with AIDS. There were 35 viral, 23 bacterial, 19 mycotic (fungal), and 13 parasitic infections among these 23 children. Nineteen of the 23 patients died of infection. Fatal infections were due to Pneumocystis carinii in eight patients, viruses in eight, bacteria in five, and Aspergillus fumigata (a fungus) in one. The variety of infectious microorganisms and the severity of resulting illnesses in the patients with AIDS were similar to those in patients with SCID and to those reported to date for children SCID. Clinical data on the role of various infectious agents in the sickness and death of 23 children with severe immune deficiency diseases, 8 of whom had AIDS, are presented. Pathogens in children with AIDS and SCID are compared. The 23 study subjects included 15 children in Montreal, Quebec, with SCID and 8 with AIDS seen between 1966 and 1985, 20 of them since 1975. 1) Populations: Pediatric Cases (IA4), 2) Diagnostic Definitions of AIDS: Opportunistic Infections (IIIA2), 3) Geographic Trends: Canada (IB1) 1A4-Lau-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Pahwa, Savita, MD; Kaplan, Mark, MD; Fikrig, Senih, MD; Pahwa, Rajendra, MD; Sarngadharan, M.G., PhD; Popovic, Mikulas, PhD; Gallo, Robert C., MD. Spectrum of Human T-Cell Lymphotropic Virus Type III Infection in Children: Recognition of Symptomatic, Asymptomatic, and Seronegative Patients. Journal of the American Medical Association, 2 May 1986, Vol. 255, No. 17: 2299-2305. Departments of Pediatrics (Pahwa, S., Pahwa, R.), and Medicine (Kaplan), North Shore University Hospital, Cornell University Medical College, Manhasset, New York; the Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Gallo, Popovic); Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland (Sarngadharan); the Department of Pediatrics, Downstate Medical Center, Brooklyn, New York (Fikrig). This study examined the clinical and immunologic spectrum associated with human T-cell lymphotropic virus type IlI/lymphadenopathy- associated virus (HTLV-III/LAV) infection in children and studied their family units. Thirty-six children were identified with serologic or virologic evidence of HTLV-II infection and were clinically divided into three groups: AIDS, AIDS-related complex (ARC), and asymptomatic. A wide clinical spectrum was noted, ranging from asymptomatic (seven children) to symptomatic, including 14 children with AIDS. All symptomatic children who were HTLV-III antibody negative had v'rologic evidence of HTLV-III infection. All 20 mothers who were studied were HTLV-II antibody positive and had immunologic abnormalities, but only 9 were symptomatic. Of 6 fathers, 4 were seropositive and all 4 had immunologic abnormalities; one of these men was clinically healthy. Seven of 16 children from families in which either sibling or a parent was initially identified as the index patient showed evidence of HTLV-II infection but were apparently healthy. Study findings suggest that apparently healthy women may transmit HTLV-III/LAV to their offspring. Immunologic and serologic testing was performed to delineate the clinical and immunologic spectrum associated with HTLV-II infection. Family members were studied when possible. A total of 45 children and 25 adults were studied. (One other adult was identified but was not included in the study.) Subjects included pediatric referrals to medical centers in Nassau County (Long Island) and Brooklyn, New York, for illnesses subsequently established to be associated with HTLV-II/LAV infection, healthy siblings of symptomatic children, and healthy offspring of adults who had been diagnosed as having AIDS or ARC or being antibody positive. Parents of pediatric patients were studied whenever possible. 1) Populations: Pediatric Cases (IA4), 2) Transmission: Perinatal (IID), 3) Transmission: Casual Contact (IIF) 1A4-Pah-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Ammann, Arthur J., MD; Kaminsky, Lawrence, MD; Cowan, Morton, MD; Levy, Jay A., MD. Antibodies to AIDS-Associated Retrovirus Distinguish Between Pediatric Primary and Acquired Immunodeficiency Diseases. Journal of the American Medical Association, 7 June 1985, Vol. 253, No. 21: 3116-3118. Pediatric Immunology/Rheumatology Division and Cancer Research Institute, University of California School of Medicine, San Francisco Medical Center, San Francisco, California. Pediatric patients with abnormal immune function were investigated to see whether they had antibodies to AIDS-associated retrovirus (ARV; also known as lymphadenopathy-associated virus and human T-cell lympho- tropic virus type II). All but 7 of 68 patients conformed to the World Health Organization (WHO) classification for immunodeficiency disease. These seven had T-cell immunodeficiency, as in AIDS cases, and six of the seven had antibody to ARV as well as risk factors associated with AIDS. The one patient without ARV antibodies had no AIDS risk factors either. No ARV antibody was detected in 61 patients with other primary immunodeficiency disorders. The authors conclude that ARV first appeared in this population of pediatric patients prior to 1978, rather than appearing as an opportunistic infection in other immunodeficiency disorders. Detection of the AIDS retrovirus is of value in identifying infants and children who may have AIDS. Blood samples of patients fitting WHO definitions of immunodeficiency disorders were studied for ARV antibodies and AIDS risk factors. Blood samples were obtained between 1971 and 1984. Descriptive findings are presented. A group of 68 children fitting WHO immunodeficiency definitions were studied. All but 3 patients were younger than 18 years of age. 1) Populations: Pediatric Cases (IA4), 2) Immunological Aspects (IIIE) 1A4—Amm-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Rosner, F.; Forgel, M.; Telsey, A.; Citerman, Stephanie; Charytan, M.; Rubinstein, A. Acquired Immunodeficiency Syndrome (AIDS) in Infants and Children: Report of Nine Cases. Biomedicine & Pharmacotherapy, 1985, Vol. 39: 350-355. Department of Medicine (Rosner), Pediatric House Staff and Medical Education, Schneider's Children Hospital, New York (Forgel); Department of Pediatrics, Queens Hospital Center Affiliation, New York (Telsey, Citerman); Long Island Jewish Hillside Medical Center, Jamaica; Division of Allergy and Immunology (Charytan, Rubinstein), Albert Einstein College of Medicine, Bronx, New York. To identify the unique features of pediatric AIDS cases, one |3-year-old white male hemophiliac and eight infants were studied for clinical symptoms and immune system function. The hemophiliac demonstrated failure to thrive, lymphadenopathy, interstitial pneumonia, recurrent bacterial infections, oropharyngeal thrush, and Pneumocystis carinii pneumonia (PCP) and died 9 months after the onset of AIDS. Clinical symptoms in the eight infants were as follows: four had low birth weight, six had failure to thrive, all had hepatosplenomegaly (enlargement of the liver and spleen), six had lymphadenopathy, seven had interstitial pneumonia, three had parotitis (inflammation of the parotid gland), three had chronic diarrhea, five had recurrent bacterial infections, seven had oropharyngeal thrush, and four had opportunistic infections (Mycobacterium avium-intracellulare, PCP, or cytomegalovirus). Four infants died of bacterial sepsis. None of the patients had lymphopenia. All had low helper/suppressor T-cell ratios and poor in vitro lymphocyte responses to pokeweed mitogens. Although many clinical features are similar between adult and pediatric AIDS cases, unique aspects of pediatric AIDS are the absence of lymphopenia and the high prevalence of recurrent bacterial infections and sepsis. Management programs for pediatric AIDS are similar to adult programs directed at eradication of opportunistic infection. This study is based on case reports, including inpatient data (clinical evaluation and immunologic testing). Serum immunoglobulin A, G, and M levels were measured by radial immunodiffusion of blood samples with specific antisera. Helper (T4) and suppressor (T8) T-cell subpopulations were analyzed by immunofluorescence with monoclonal antibodies. Nine children with AIDS were studied: one 13-year-old hemophiliac and eight infants (three black females, one black Haitian female, one white male, and three black males). Of the eight infants, four had received blood transfusions, three had maternal intravenous drug use as a risk factor, and one had a father with AIDS. 1A4-Ros-5 Policy Keys: 1) Populations: Pediatrics Cases (IA4), 2) Diagnostic Definitions of AIDS: Opportunistic Infection (I[IA2) Author(s): Title: Source: Institution: Findings: Method: Ultmann, Monica H.; Belman, Anita L.; Ruff, Holly A.; Novick, Brian E.; Cone-Wesson, Barbara; Cohen, Herbert J.; Rubinstein, Arye. Developmental Abnormalities in Infants and Children with Acquired Immune Deficiency Syndrome (AIDS) and AIDS-Related Complex. Developmental Medicine and Child Neurology, 1985, Vol. 27: 563-571. Departments of Developmental Pediatrics (Ultmann) and Pediatrics (Ruff, Novick, Cohen, Rubinstein), Albert Einstein College of Medicine, Bronx, New York; Department of Neurology, School of Medicine, State University of New York, Stony Brook, New York (Belman); Department of Otolaryngology, University of Southern California School of Medicine, Los Angeles, California (Cone-Wesson). Developmental abnormalities were examined in seven pediatric AIDS patients and nine pediatric AIDS-related complex (ARC) patients. Abnormalities were more severe in the AIDS patients than in the ARC patients. Three of the AIDS patients got worse during the study; ARC patients did not. Most AIDS and ARC patients had recurring infections, respiratory difficulties, failure to thrive, and chronic diarrhea, indicating that nutritional and metabolic factors may have contributed to developmental delays. Most patients in both study groups had lowered helper/suppressor T-cell ratios. Multiple medications used to treat bacterial and opportunistic infections may have had adverse side effects. The majority of both AIDS and ARC patients had interstitial lung disease; several had digital clubbing (broadening and thickening of ends of fingers, seen in chronic pulmonary disease). Of the ARC patients, four had normal language skills and two had normal motor skills, while all seven AIDS patients showed delay in developing or regression in both skills. The neurological findings showed that three of the seven AIDS patients had evidence of progressive encephalopathy (brain disease), and six AIDS patients showed neurological deficits. In contrast, six of the nine ARC patients had normal neurologic examinations. Intelligence tests showed that, of the eight ARC patients examined, one had normal intelligence and three were borderline, while the remaining four were mildly to severely retarded. None of the seven AIDS patients had normal intelligence, and only one was borderline. Patients were evaluated at l- to 3-month intervals or as clinically indicated. Birth history and developmental milestones were obtained from the parent, guardian, or hospital chart. To assess cognitive function, Bayley Scales of Infant Development were administered to children less than 30 months of age and the Stanford-Binet Intelligence Test to older children. Denver Developmental Screening Tests were administered to patients each time they were seen. Children older than 12 months were given the Preschool Language Scale test. Serial neur- ological examinations were performed. Computerized axial tomographic scans, electroencephalograms, and brainstem auditory evoked potentials were done for as many children as possible. Complete blood counts, electrolyte determinations, and liver function tests were performed on a regular basis. Immunological studies and viral antibody determinations 1A4-Ult-6 Sample Size: Policy Keys: were done for each patient. Biopsy material was obtained when indicated. The patient group consisted of 16 pediatric patients, 7 with AIDS and 9 with ARC who were monitored beginning in July 1983 and September 1984, respectively. All of the subjects were inpatients or outpatients at the Division of Pediatric Immunology of the Albert Einstein College of Medicine (Bronx, New York). All the patients were from the five boroughs of New York City. Nine patients were male and seven were female, ranging in age from 6 months to 6 years. Since the study began, one patient with ARC developed AIDS and three AIDS patients died. The parental risk factors for each child included three children born to mothers with AIDS and seven children with mothers with abnormal immune profiles at the time their children were diagnosed; risk factors for the others were unknown. 1) Populations: Pediatric Cases (IA#4), 2) Other Clinical Manifestations: Developmental Abnormalities (I[IA4) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Thomas, Pauline A., MD; Jaffe, Harold W., MD; Spira, Thomas J., MD; Reiss, Rebecca, MS; Guerrero, Isabel C., MD; Auerbach, David, MD. Unexplained Immunodeficiency in Children: A Surveillance Report. Journal of the American Medical Association, 3 August 1984, Vol. 252, No. 5: 639-644. New York City Department of Health (Thomas, Reiss); Division of Field Services, Epidemiologic Program Office, Centers for Disease Control, New York City Health Department (Thomas) and Los Angeles Health Department (Auerbach); Acquired Immunodeficiency Syndrome Program (Jaffe) and Division of Host Factors (Spira), Centers for Disease Control, Atlanta, Georgia; New Jersey State Department of Health, Trenton, New Jersey (Guerrero). From October 1982 to October 1983, the Centers for Disease Control (CDC) received reports of 35 children meeting the CDC definition of AIDS. All had serious opportunistic infections. The 35 children lived in 10 different states, clustered in five major metropolitan areas. Three of the children had a parent with AIDS, and one had received a blood transfusion from a person in whom AIDS later developed. Most of the children had at least one parent in a high-risk population group. Many of the children had histories of pre-AIDS symptoms, including Pneumocystis carinii pneumonia, lymphadenopathy and oral thrush (fungus infection). The average age at onset was 5 months, and the average age at diagnosis was 12 months. To determine whether opportunistic infection in children without known reason for immunodeficiency was truly a new phenomenon, a review was made of requests to the CDC for the drug pentamidine (a treatment for P. carinii pneumonia for which CDC is the sole distributor). This review revealed an apparent increase from 1979 to 1983 of P. carinii infection in children. This study is based on surveillance reports and epidemiological studies. All children (35 total) with AIDS reported to the CDC from | October 1982 to | October 1983 were studied. 1) Populations: Pediatric Cases (IA4), 2) Incubation Period (Pediatric) (IIIC), 3) Diagnostic Definitions of AIDS: Opportunistic Infections (IIIA2) 1A4-Tho-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lapointe, Normand; Gurbindo, Dolores; Chad, Zave; Matheson, David; Rousseau, Elisabeth; Joncas, Jean; Montplaisir, Serge; Michaud, Jean; St- Cyr, Claire. Twelve Children with AIDS and Their Families. In Griscelli, C. and Vossen, J. (ed.), Progress in Immunodeficiency Research and Therapy. Amsterdam, The Netherlands, Excerpta Medica, 1984, pp. 345-350. Service of Immunology-Allergy-Rheumatology, Department of Pediatrics, Department of Pathology and Microbiology and Immunology, Ste-Justine Hospital, University of Montreal; Department of Pediatrics, University of Calgary. Twelve children from 10 families, each with AIDS or AIDS-related complex (ARC), were seen in Montreal between April 1981 and October 1983. Prior to that, no such patients had been seen in this practice. Eleven patients were referred with symptoms of AIDS, and one family was referred because one of the parents had AIDS. The cluster was composed of seven recent Haitian immigrant families, one Caucasian Dominican family who lived in Haiti before coming to Canada, and a Caucasian child who received two blood transfusions at birth from five different donors. AIDS was found in seven females and five males; the diagnosis was made before 6 months of age for seven patients and in all patients before 3 years of age. Most patients presented with bouts of unexplained fever, failure to thrive, and recurrent respiratory infections. Oral candidiasis was also present in most cases. Lymphadenopathy was also common, as was progressive pneumonia. Cytomegalovirus was detected in most patients, and a peculiar central nervous system disease was noted in half the patients. In some patients T-cells were decreased, and anemia was often found. One group of patients had rapid demise with overwhelming infection, while a second group experienced chronic courses with periodic severe infection. AIDS may be acquired by blood products, as in one of these cases, or by vertical transmission (seven mothers had abnormal immune findings, and one mother died of AIDS). The mothers and fathers of the transfused child and an adopted Haitian child were normal. Two fathers died of AIDS, and three others had Immunological abnormalities. No history of homosexuality, drug abuse, or promiscuity was noted in these families. This study consisted of case reports of 12 pediatric AIDS cases. A total of 12 children from 10 Montreal families, each with AIDS or ARC, were studied. 1) Populations: Pediatric Cases (IA4), 2) Transmission: Perinatal (IID), 3) Clinical Manifestations: Opportunistic Infections (Pediatric) (IlIA2), 4) Transmission: Casual Contact (IF) 1A4-Lap-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Rubinstein, Arye, MD; Sicklick, Marc, MD; Gupta, Asha, MD; Bernstein, Larry, MD; Klein, Norman, MD; Rubinstein, Ethan, MD; Spigland, Ilya, MD; Fruchter, Lazar, MD; Litman, Nathan, MD; Lee, Haesoon, MD; Hollander, Melvin, MD. Acquired Immunodeficiency with Reversed T,/Tg Ratios in Infants Born to Promiscuous and Drug-Addicted Mothers. Journal of the American Medical Association, 6 May 1983, Vol. 249, No. 17: 2350-2356. Departments of Pediatrics and Microbiology and Immunology, Division of Clinical Allergy and Immunology (A. Rubinstein, Sicklick, Gupta, Bernstein, Klein, E. Rubinstein, Spigland, Fruchter, Litman), Albert Einstein College of Medicine, Bronx, New York; Department of Pediatrics, Jewish Hospital and Medical Center, Brooklyn, New York (Lee); Department of Pediatrics, Misericordia Hospital Medical Center, Bronx, New York (Hollander). This study reports an immunodeficiency syndrome in infants comparable to the syndrome that had previously, and only recently, been reported for adults. Seven children who were small for gestational age at birth subsequently failed to thrive developed lymphadenopathy, parotitis (inflammation of the parotid gland), pneumonia, and recurrent infections. All had profound immunodeficiency with lowered helper/suppressor T-cell ratios. Three mothers had immunodeficiency similar to that found in their infants. One mother died at age 33 years of AIDS. In five of the children and three of their mothers, there was also evidence of Epstein- Barr virus infection. This study consists of clinical case reports supplemented by blood tests of immune system function. Duration of follow-up ranged from | to 33 months. Seven immunodeficient New York children and their mothers (five of whom were sexually promiscuous and/or drug addicts) were studied. 1) Populations: Pediatric Cases (IA4), 2) Transmission: Perinatal (IID) 1A4-Rub-9 I. Prevalence and Spread of AIDS/HTLV-III/LAV A. Population Studies and Groups at Risk 5. Minorities Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Acquired Immunodeficiency Syndrome (AIDS) Among Blacks and Hispanics--United States. Morbility and Mortality Weekly Report, 24 October 1986, Vol. 35, No. 42: 655-666. Centers for Disease Control, Atlanta, Georgia. Of the 24,576 patients meeting the AIDS case definition for national reporting between | June 1981 and 8 September 1986, 6,192 (25%) were black and 3,488 (14%) were Hispanic, whereas these groups represent only 12% and 6%, respectively, of the U.S. population. The proportion of cases by racial or ethnic group has remained relatively constant over time. For adults, the overall cumulative incidences (number of cases per 1,000,000 population of that racial or ethnic group) were 3.1 and 3.4 times higher for blacks and Hispanics, respectively, than for whites. Of the black and Hispanic patients, 62% and 65%, respectively, resided in New York, New Jersey, or Florida, as did 33% of the white patients. Approximately half of the black and Hispanic patients from New York and New Jersey were intravenous drug abusers, and 40% of the blacks from Florida were born in Haiti. Among the men, blacks and Hispanics accounted for 23% and 14%, respectively, while among the women, they accounted for 51% and 21%, respectively. Among homosexual and bisexual male AIDS patients, 16% were black, 11% were Hispanic, and 73% were white. Among heterosexuals in all other transmission categories, 50% were black, 25% were Hispanic, and 25% were white. Of the 350 AIDS patients under 15 years of age whose race or ethnicity was known, 204 (58%) were black and 77 (22%) were Hispanic. They also were more likely than white children with AIDS to reside in New York, New Jersey, or Florida. Ninety percent of the children with perinatally acquired AIDS were black or Hispanic, compared with 42% of the children with hemophilia- or transfusion-associated AIDS. The overall incidence for black and Hispanic children was 15.1 and 9.1 times, respectively, the incidence for white children. This study reports the surveillance of AIDS cases from 1 June 1981 to 8 September 1986 by racial or ethnic group. The 24,576 patients in the U.S. meeting the AIDS case definition for national reporting are reviewed. 1) Populations: Minorities (IA5), 2) Geographic Trends: U.S. (IB1) 1A5-Cen-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Maayan, Shlomo, MD; Wormser, Gary P., MD; Hewlett, Dial, MD; Miller, Steven N., MD; Duncanson, Frederick P., MD; Rodriguez, Angela, MD; Perla, Elliott N., MD; Koppel, Barbara, MD; Rieber, Egmond E., MD. Acquired Immunodeficiency Syndrome (AIDS) in an Economically Disadvantaged Population. Archives of Internal Medicine, September 1985, Vol. 145: 1607-1612. Division of Infectious Diseases, Department of Medicine, Metropolitan and Lincoln Hospital Centers and Westchester County (New York) Medical Center, New York Medical College, Valhalla, New York. This study investigated features of AIDS that might be unique to low- income urban populations. A total of 40 AIDS patients, 70% of whom were intravenous drug abusers, were seen over a 20-month period (July 1981 to February 1983) at two New York City hospitals. Most of the patients came from two inner-city sections of New York City and from nearby correctional institutions. A total of 85% of the patients were black or Hispanic. Unique features of AIDS in this largely heterosexual, low-income population were the high incidence of opportunistic infections (90%), the low incidence of Kaposi's sarcoma (10%), and the high mortality rate (34% died during initial hospitalization and 74% by the l-year follow-up date). The authors suggest that AIDS should be considered in all intravenous drug abusers with oral thrush, shortness of breath, pneumonia, or extrapulmonary tuberculosis. This study consists of case reports and follow-up of 40 hospitalized New York AIDS patients. Blood tests performed included total white blood cell and lymphocyte counts; T-cell enumeration with OKT3, OKT4, and OKT8 monoclonal antibodies; skin sensitivity to purified protein derivative, Candida, and mumps virus; and serum antibody to Epstein- Barr virus by indirect immunofluorescence (IFA), cytomegalovirus by enzyme-linked immunosorbent assay, herpes simplex virus by comple- ment fixation, and Toxoplasma gondii by IFA. Viral culture tests were done on samples of nasal secretions, urine, and brain tissue. A total of 40 AIDS patients, 70% of whom were intravenous drug abusers, were studied at two New York City hospitals where they were inpatients in the period July 1981 to February 1983. Most of the patients came from two inner-city sections of New York City and from nearby correc- tional institutions. Twenty-four (60%) of the patients were Hispanic, 10 (25%) were black, and 6 (15%) were white; they ranged in age from 20 to 39 years (mean, 32). 1) Populations: Minorities, [.V. Drug Abusers (IA5,2), 2) Diagnostic Definitions of AIDS: Opportunistic Infections (IIIA2) 1A5-Maa-2 Author(s): Title: Source: Institution: Findings: Pitchenik, Arthur E., MD; Cole, Clifford, MD, MPH; Russell, Bertrand W., BS; Fischl, Margaret A., MD; Spira, Thomas J., MD; Snider, Dixie E., Jr., MD. Tuberculosis, Atypical Mpycobacteriosis, and the Acquired Immuno- deficiency Syndrome Among Haitian and Non-Haitian Patients in South Florida. Annals of Internal Medicine, November 1984, Vol. 101, No. 5: 641-645. Department of Medicine, Divisions of Pulmonary and General Medicine, University of Miami School of Medicine, Miami, Florida; Florida Department of Health and Rehabilitative Services (Community Tuberculosis Control Services), Jacksonville, Florida; Division of Host Factors, Center for Infectious Diseases and Division of Tuberculosis Control, Center for Prevention Services, Centers for Disease Control, Atlanta, Georgia. In this study, the association between mycobacterial disease and AIDS was determined by reviewing the records of all cases of tuberculosis (TB) and all cases of AIDS reported in Dade County, Florida, from January 1980 through June 1983. There is a relatively high prevalence of TB among Haitians entering southern Florida compared with the U.S. popu- lation as a whole. Disseminated TB is common among Haitians with AIDS. TB was diagnosed in 27 of 45 Haitians with AIDS but in only 1 of 37 non- Haitians with AIDS. Among the 27 Haitians with AIDS and TB, 19 had extrapulmonary TB, whereas among 286 Haitian patients with TB without AIDS, only 56 had extrapulmonary TB. In patients with both, TB preceded AIDS by | to 17 months in 22 patients. The frequency of disseminated atypical mycobacteriosis or positive sputum cultures was not significantly different between Haitian (11.3%) and non-Haitian (8.3%) AIDS patients. The higher proportion of TB among Haitian AIDS patients probably reflects the higher general incidence of TB in Haitians. TB may precede the opportunistic infections characteristic of AIDS simply because TB is caused by a more virulent organism and would be expected to manifest at an earlier stage of immunosuppression. Even in AIDS patients, TB responds well to drug therapy. TB among Haitian patients with AIDS is much more common than TB among non-Haitian patients with AIDS, and it is also more common than atypical mycobacteriosis among Haitian or non-Haitian AIDS patients. A high proportion of all Haitian patients aged 21 to 50 who contract extrapulmonary or disseminated TB also contract other serious infections or Kaposi's sarcoma concurrently or shortly thereafter. 1A5-Pit-3 Method: Sample Size: Policy Keys: This was a two-way case-control study of all TB and all AIDS patients in Dade County, Florida. Haitians in each group were compared with non- Haitians, and the two disease groups (and Haitians therein) were compared with each other. Dade County patients aged 21 to 50 years with verified TB, who were counted from | January 1980 through June 1983 and all 82 Dade County AIDS patients identified from January 1980 through June 1983 were included. All patients with AIDS and tuberculosis had been hospitalized in Jackson Memorial Hospital. 1) Populations: Minorities (Haitians) (IA5), 2) Other Clinical Manifestations: Tuberculosis (IIIA4), 3) Cofactors: Tuberculosis (IC3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Pitchenik, Arthur E., MD; Fischl, Margaret A., MD; Dickinson, Gordon M., MD; Becker, Daniel M., MD; Fournier, Arthur M., MD; O'Connell, Mark T., MD; Colton, Robert M., MD; Spira, Thomas J., MD. Opportunistic Infections and Kaposi's Sarcoma Among Haitians: Evidence of a New Acquired Immunodeficiency State. Annals of Internal Medicine, March 1983, Vol. 98, No. 3: 277-284. Divisions of General Medicine and Infectious Diseases, Department of Medicine, University of Miami School of Medicine, Miami, Florida; Division of Host Factors, Centers for Disease Control, Atlanta, Georgia. Hospitalized Haitian patients who had evidence of opportunistic infections or Kaposi's sarcoma (KS) were observed and compared with previously described AIDS cases. Malnutrition did not appear to be the cause of this syndrome, although it may have been a contributing fac- tor. The use of medicinal roots and herbs was also unlikely to be a cause. The syndrome among Haitian patients is strikingly similar to that reported among homosexual men. Both groups show depressed numbers of helper T cells and an inverted helper/suppressor T-cell ratio. The same opportunistic infections and KS are also found in both groups. A similar high rate of positive results on serologic tests for cytomegalovirus, Epstein-Barr virus, and hepatitis B virus was also noted. In contrast, the Haitian patients were not homosexual, had no history of drug abuse, and denied any genital-anal or oral-anal contact. This is the first report of an outbreak of AIDS among heterosexuals who are not intravenous drug abusers. The fact that it has occurred in a specific subpopulation is of epidemiologic significance. In this study, all Haitian patients admitted to the medical service of Jackson Memorial Hospital from | January 1982 to 20 June 1982 were evaluated prospectively. These patients were interviewed and had a physical examination. Medical histories were also obtained, and routine laboratory tests were performed, including immunologic and virologic studies. Medical records of Haitian patients admitted to the same hospital from 1 April 1980 to 31 December [981 were reviewed retrospectively. Eleven Haitians were studied prospectively, and nine were studied retrospectively. All were current residents of the Miami-Dade area in Florida, and all were born and raised in Haiti. Of these 20 patients, 17 were men (mean age, 28 years; range, 22 to 42 years), and 3 were women (ages 22, 26, and 43 years). A control group of healthy Haitians selected from hospital personnel was matched for age and sex to the patients evaluated prospectively. 1) Populations: Minorities, Heterosexuals ([A5,6), 2) Geographic Trands: Haiti (IB2), 3) Transmission: Sexual Activity (IIA), 4) Cofactors: Malnutrition (IC3) 1A5-Pit-4 3 Ee? oo I. Prevalence and Spread of AIDS/HTLV-III/LAV A. Population Studies and Groups at Risk 6. Heterosexuals Author(s): Title: Source: Institution: Findings: Method: Kreiss, Joan K., MD, MSPH; Koech, Davy, PhD; Plummer, Francis A., MD; Holmes, King K., MD, PhD; Lightfoote, Marilyn, PhD; Piot, Peter, MD, PhD; Ronald, Allan R., MD; Ndinya-Achola, J.0., MB, ChB; D'Costa, Lourdes, J., MB, ChB; Roberts, Pacita, MS; Ngugi, Elizabeth N.; Quinn, Thomas C., MD. AIDS Virus Infection in Nairobi Prostitutes: Spread of the Epidemic to East Africa. The New England Journal of Medicine, 13 February 1986, Vol. 314, No. 7: 414-418. Division of Infectious Diseases, Department of Medicine, and Department of Biostatistics, University of Washington, Seattle; Kenya Medical Research Institute, Nairobi City Commission Special Treatment Clinic, Ministry of Health, and Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium. AIDS is epidemic in central Africa. To determine the prevalence of AIDS virus infection in East Africa, prostitutes, men treated at a clinic for sexually transmitted diseases, and healthy medical personnel in Nairobi, Kenya, were studied. Antibody to human T-cell lymphotropic virus type III (HTLV-II) was detected in the serum of 42 of 64 (66%) prostitutes of low socioeconomic status, 8 of 26 (31%) prostitutes of higher status, 3 of 40 (8%) male clinic patients, and | of 42 (2%) control subjects. In all groups the mean helper/suppressor T-cell ratios were significantly lower in seropositive than in seronegative subjects. None of the subjects had opportunistic infections, Kaposi's sarcoma, fever, weight loss, diarrhea, or fatigue. However, generalized lymphadenopathy was detected in over half of the seropositive subjects. Sexual exposure to men of different nationalities was associated with different rates of positivity for antibody to HTLV-III, ranging from a relative risk of 8.73 for sexual exposure to partners from Rwanda (central Africa) to a relative risk of 0.80 (insignificant) for sexual exposure to North Americans and Europeans. Seropositive prostitutes tended to have a higher prevalence of sexually transmitted diseases than did seronegative prostitutes. The high prevalence of HTLV-III antibody among prostitutes 1s surprising considering the few cases of overt AIDS diagnosed in Kenya. Sexual exposure to men from central Africa was significantly associated with HTLV-II antibody positivity among prostitutes, suggesting transcontinental spread of the epidemic. For each subject, a standard questionnaire was administered, a physical examination was performed, and a blood sample was drawn. The prostitutes also underwent pelvic examination. T-cell subsets were quantitated by Leu-2, Leu-3, and Leu-4 monoclonal antibodies. Sera were tested for antibody to HTLV-IIl by two commercially available enzyme-linked immunosorbent assays and by Western blot. A subject was 1A6-Kre-1 Sample Size: Policy Keys: considered seropositive for HTLV-III if both an immunoassay and the Western blot test were positive. A total of 172 Kenyan subjects participated. Of these, 64 were prostitutes from an economically depressed neighborhood in Nairobi. Their mean age was 29 years, mean duration of prostitution was 5 years, and mean length of residence in Nairobi was 6 years. These women had an average of 963 sexual encounters per year with clients who were mostly of Kenyan nationality. They performed only vaginal intercourse without oral or anal sex, and none used barrier forms of contraception. Another 26 prostitutes of higher socioeconomic status were recruited from the bar of a tourist hotel. Their mean age was 24 years, and mean length of residence in Nairobi was 5 years. These women catered to tourists and traveling businessmen from Africa, Europe, and North America, as well as well-to-do Kenyans. They had an average of 124 paid sexual encounters per year. Seven women performed active oral sex, but none practiced anal intercourse. No barrier forms of contraception were used. Forty men presenting to the Nairobi Special Treatment Clinic with genitourinary symptoms were also enrolled. Their mean age was 29 years. During the previous year these men had had an average of 17 sexual partners, and 23 of them had had intercourse with one or more prostitutes. None used condoms. Forty-two medical students, laboratory technicians, and other medical personnel were enrolled as controls. This group comprised 18 women and 24 men, with a mean age of 26 years. 1) Populations: Heterosexuals (Prostitutes) (IA6), 2) Geographic Trends: Eastern Africa (Kenya) (IB5), 3) Risk Reduction: Condoms (VA2) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Clumeck, Nathan, MD; Robert-Guroff, Marjorie, PhD; Van De Perre, Philippe, MD; Jennings, Andrea, PhD; Sibomana, Jean, MD; Demol, Patrick, MD; Cran, Sophie, MD; Gallo, Robert C., MD. Seroepidemiological Studies of HTLV-II Antibody Prevalence Among Selected Groups of Heterosexual Africans. Journal of the American Medical Association, 8 November 1985, Vol. 254, No. 18: 2599-2602. Division of Infectious Diseases and Laboratory of Microbiology, Saint- Pierre Hospital, Brussels, Belgium (Clumeck, Van De Perre, Demol, Cran); Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Robert-Guroff, Jennings, Gallo); Blood Transfusion Project, Kigali, Rwanda (Sibomana). Heterosexual transmission of AIDS was examined by studying T-cell ratios and human T-cell lymphotropic virus type III (HTLV-II) infection in African patients with AIDS or AIDS-related complex (ARC) and in female prostitutes. HTLV-III infection was noted in 46 of 53 (87%) patients with AIDS, in 29 of 33 (88%) patients with ARC, in 67 of 84 (80%) prostitutes, in 5 of 40 (12.5%) healthy controls, and in 8 of 51 (15.5%) blood donors. Patients with AIDS or ARC had lower helper/suppressor T-cell ratios than healthy controls. The authors suggest that HTLV-II infection has already spread extensively into the general African population and that female prostitutes could be an important human reservoir of AIDS virus in the heterosexual population. This was a seroepidemiological case-control study of heterosexual Africans infected with HTLV-II and a group of Rwandan prostitutes. T- cell subpopulations were quantified by indirect immunofluorescence of blood samples with OKT3, OKT4, and OKT8 monoclonal antibodies. Blood serum samples were tested for HTLV-II antibodies by enzyme- linked immunosorbent assay, with borderline cases confirmed by Western blot. The study sample consisted of 53 heterosexual African AIDS patients, 33 heterosexual ARC patients, and 84 Rwandese prostitutes. Forty healthy central Africans residing in Brussels were matched with the AIDS patients for age and sex and served as a control group. Also studied were 51 unselected African blood donors at a Red Cross center in Kigali, Rwanda. 1) Populations: Heterosexual (Prostitutes) (IA6), 2) Geographic Trends: Africa (Rwanda) (IB5), 3) Populations: General African Population (IA7), 4) Transmission: Sexual Activity (IIA) 1A6-Clu-2 Author(s): Title: Source: Institution: Findings: Method: Redfield, Robert R., MD; Markham, Phillip D., PhD; Salahuddin, Syed Zaki, MS; Wright, D. Craig, MD; Sarngadharan, M.G., PhD; Gallo, Robert C., MD. Heterosexually Acquired HTLV-III/LAV Disease (AIDS-Related Complex and AIDS): Epidemiological Evidence for Female-to-Male Transmission. Journal of the American Medical Association, 18 October 1985, Vol. 254, No. 15: 2094-2096. Departments of Virus Diseases (Redfield) and Medicine (Wright), Walter Reed Army Institute of Research, Washington, DC; Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland (Markham, Sarngadharan); Laboratory of Tumor Cell Biology, National Institutes of Health, Bethesda, Maryland (Gallo, Salahuddin). This study was undertaken to document heterosexual transmission of the AIDS virus. Of 41 patients with human T-cell lymphotropic virus type III (HTLV-II) disease evaluated at Walter Reed Medical Center, 15 (37%) acquired their infection from a partner(s) of the opposite sex. The demographic features of these 15 patients (10 males and 5 females) differed substantially from those of AIDS patients reported to the Centers for Disease Control (CDC). Heterosexual contact with partners who developed AIDS or were at risk for AIDS was confirmed for six patients. The remaining nine patients had multiple (over 50) heterosexual partners and/or sexual contacts with prostitutes. Only two male patients engaged in occasional insertional anal intercourse with their heterosexual partners, and all five females denied receptive anal intercourse. Two patients (13%) had evidence of previous exposure to syphilis; 7 of 15 had evidence of previous hepatitis B virus infections; evidence of of previous cytomegalovirus and Epstein-Barr virus infections was common (73% and 87%, respectively). The method of sexual activity was apparently not related to disease acquisition; this study clearly demonstrates that receptive anal intercourse is not a requirement for transmission of HTLV-II. These data are further evidence for the occurrence of bidirectional heterosexual transmission (both male to female and female to male) of HTLV-II infection and disease. This was an epidemiologic study of sexual contacts of heterosexual AIDS and ARC patients. Serum or plasma samples were tested for HTLV-III antibody by enzyme-linked immunosorbent assay and Western blot; blood tests were also run for antibody to hepatitus virus types A and B, cytomegalovirus, and Epstein-Barr virus and for signs of previous infection with Treponema pallidum. All patients were interviewed on several occasions to ascertain possible AIDS risk factors; family members and acquaintances were interviewed when available. Clinical assessments were also made. 1A6-Red-3 Sample Size: A total of 41 HTLV-IlI-positive patients with AIDS or ARC who were patients at the Walter Reed Army Medical Center in Washington, D.C., were studied. Policy Keys: 1) Populations: Heterosexuals (males and females) (IA6), 2) Transmission: Sexual Activity (IIA), 3) Cofactors: Other Infections (IC3) Author(s): Title: Source: Institution: Findings: Method: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Heterosexual Transmission of Human T-Lymphotropic Virus Type [lI/Lymphadenopathy-Associated Virus. Morbidity and Mortality Weekly Report, 20 September 1985, Vol. 34, No. 37: 561-363. Centers for Disease Control, Atlanta, Georgia. AIDS is caused by a virus (human T-cell lymphotropic virus type [1I/lymphadenopathy-associated virus, HTLV-III/LAV) that is known to be transmitted through sexual contact and parenteral (intravenous or through the skin) exposure to blood or blood products and from mother to child during the perinatal (before, during, and after birth) period. In the U.S., sexual contact is believed to be the only risk factor for 8,374 (64%) of the 13,061 AIDS cases among adults reported to the Centers for Disease Control (CDC) as of 16 September 1985. These sexual contact cases include 8,241 homosexual or bisexual men and 133 heterosexual men and women. The heterosexual contact cases are among people who denied any other known risk factors (parenteral exposure to blood or blood products or transmission from mother to child during the perinatal period), but reported sexual contact with a risk group member or an AIDS patient of the opposite sex. No risk factor has been identified in 829 cases. Of these, 344 patients were born in developing countries where AIDS is known to exist. Of the remaining 485 patients, 99 were available for in-depth interviews. Twenty-three (34%) of the 68 men had histories of sexual contact with female prostitutes. One (3%) of the women had a history of prostitution. Serologic evidence of HTLV-III/LAV antibodies in female prostitutes has been found in preliminary studies in several American cities. Of 92 prostitutes tested in a Seattle study, 5 (5%) had HTLV-III/LAV antibodies. In Miami, 10 (40%) of 25 prostitutes attending an AIDS screening clinic were positive for HTLV-III/LAV antibodies. Eight of these 10 reported intravenous drug abuse. The authors point out that sexually active persons should realize that their risks of acquiring infection are greatly increased by having sexual intercourse with members of known AIDS risk groups or with persons who are the sexual contacts of risk group members. Sexually active persons should also recognize that, as with other sexually transmitted diseases, the greater the number of sexual partners, the greater the risk of possible HTLV-III/LAV infection. Consistent use of condoms should assist in preventing infection with HTLV-III/LAV, but their efficacy in reducing transmission has not yet been proven. This report reviews evidence from diverse sources for heterosexual transmission of HTLV-III/LAV, including two studies of female prostitutes in Seattle and Miami. 1A6-Cen-4 Sample Size: A subgroup of 829 AIDS cases with no known risk factor was studied from the 13,061 AIDS cases reported to the CDC as of 16 September 1985. Policy Keys: 1) Populations: Heterosexual (IA6), 2) Transmission: Sexual Activity (IIA), 3) Populations: Prostitutes (IA7) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Van de Perre, Philippe; Carael, Michel; Robert-Guroff, Marjorie; Freyens, Pierre; Gallo, Robert C.; Clumeck, Nathan; Nzabihimana, Elie; De Mol, Patrick; Butzler, Jean-Paul; Kanyamupira, Jean-Baptiste. Female Prostitutes: A Risk Group for Infection with Human T-Cell Lymphotropic Virus Type III. The Lancet, 7 September 1985, Vol. 2, No. 8454: 524-526. Saint-Pierre University Hospital, Brussels; Institute for Sociology, Free University of Brussels, Brussels, Belgium; National Cancer Institute, Bethesda, Maryland; University Center for Public Health (CUSP) and Department of Epidemiology, National University of Rwanda, Butare, Rwanda. Female prostitutes and male customers of prostitutes in Rwanda were tested for T-cell ratios and antibodies to human T-cell lymphotropic virus type III (HTLV-II). Only 6 of the 33 prostitutes were symptom free; 13 had unexplained lymphadenopathy, and 14 had lymphadenopathy and various other symptoms. The latter two groups had fewer helper T cells and low helper/suppressor T-cell ratios. HTLV-III antibodies were detected in 29 of 33 prostitutes, 4 of 33 female controls, 7 of 25 male customers, and 2 male controls. In male customers, HTLV-III antibody positivity increased according to the number of different sexual partners per year. The authors suggest that in central Africa, prostitutes are a high-risk group for HTLV-III infection. This was a case-control study of female prostitites and their male customers, who were tested for T-cell ratios and antibodies to HTLV- [II. All patients and controls answered a baseline questionnaire about demographic characteristics and number of sexual partners per month. Males were also questioned about details of sexual practices-- homosexual, bisexual, and heterosexual--and females were asked to describe the most recent 5 to 10 sexual encounters. HTLV-III antibodies were quantified by enzyme-linked immunosorbent assay, with borderline results confirmed by Western blot. T-cell subpopulations were quantified by indirect immunofluorescence with OKT4 and OKT& monocloncal antibodies. Thirty-three female prostitutes in Rwanda and 25 male customers of prostitutes were recruited from patients at a sexually transmitted disease clinic. Prostitutes ranged in age from 16 to 31 years (mean, 24), had | month to 10 years of experience in prostitution (median, 4 years), and a median of 44 sexual partners per month, with more than 95% of this activity being vaginal intercourse; 82% of prostitutes had generalized lymphadenopathy. Male customers ranged in age from 20 to 40 years (mean, 27). A group of blood donors from the Rwandere Red Cross (33 females and 27 males), none of whom were involved in prostitution, served as controls and were matched to subjects by age, sex, ethnicity, geographic origin, and annual income. All subjects were black Rwandese originating from and living in Ngoma, Rwanda, or environs; none admitted to intravenous drug use, homosexuality, or bisexuality, and none had had a blood transfusion in the last 5 years. 1A6-Van-5 Policy Keys: 1) Populations: Heterosexual Males, Prostitutes (IA6), 2) Transmission: Sexual Activity (IIA), 3) Geographic Trends: Africa (Rwanda) (IB5) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kreiss, Joan K., MD, MPH; Kitchen, Lynn W., MD; Prince, Harry E., PhD; Kasper, Carol K., MD; Essex, Max, DVM, PhD. Antibody to Human T-Lymphotropic Virus Type III in Wives of Hemophiliacs: Evidence for Heterosexual Transmission. Annals of Internal Medicine, May 1985, Vol. 102, No. 5: 623-626. Robert Wood Johnson Clinical Scholars Program, Wadsworth Veterans Administration Hospital; Cellular Immunology Laboratory, American Red Cross Blood Services; Hemophilia Center, Orthopaedic Hospital; Department of Medicine, University of Southern California, Los Angeles, California; Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts. This study was conducted to evaluate the risk of heterosexual transmission of AIDS from hemophiliacs to their female sexual partners. Twenty-one of 42 (50%) hemophiliac husbands had antibody to human T-cell lymphotropic virus type III (HTLV-II), 10 of whom had AIDS or lymphadenopathy, the latter being an indication of overt disease. None of the 42 spouses had AIDS or lymphadenopathy, but two had HTLV-III antibody. One of these two women had a marked reduction in the helper/suppressor T-cell ratio, evidence of immune system dysfunction. Both husbands of these women had HTLV-II antibody, but neither had AIDS or any AIDS symptoms as of early 1984. The two affected wives constitute 9.5% of the spouses of the 21 hemophiliacs with HTLV-III antibody. The authors conclude that transmission of HTLV-II occurs between hemophiliacs and their heterosexual partners. In this prospective study, 42 hemophiliac subjects and their wives or other heterosexual partners were interviewed and given physical exams, and blood samples were drawn for blind laboratory tests of factors related to immunological status and for antibodies to cytomegalovirus, Epstein-Barr virus, and hepatitis B virus. The presence of antibodies to HTLV-II was also determined by indirect membrane immunofluor- escence. Forty-two Los Angeles area hemophiliacs seen between November 1982 and March 1983 at a hemophilia center and their 42 wives or other permanent heterosexual partners were studied. Ages ranged from 20 to 63 years (mean, 36 years). None of the women was an intravenous drug user or of Haitian origin. Only one had received a blood transfusion since 1978. None had received an inadvertent needlestick, although 11 women reported contact with the husband's clotting-factor concentrate or injection equipment. The control group consisted of 100 age- and sex- matched Los Angeles Red Cross volunteer blood donors. 1) Populations: Heterosexuals, Hemophiliacs (IA6,3), 2) Transmission: Heterosexual Activity (IIA) 1A6-Kre-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Redfield, Robert R., MD; Markham, Phillip D., PhD; Salahuddin, Syed Zaki, MS; Sarngadharan, M.G., PhD; Bodner, Anne J., PhD; Folks, Thomas M., PhD; Ballou, William R., MD; Wright, D. Craig, MD; Gallo, Robert C., MD. Frequent Transmission of HTLV-II Among Spouses of Patients with AIDS-Related Complex and AIDS. Journal of the American Medical Association, 15 March 1985, Vol. 253, No. Ll: 1571-1573. Departments of Virus Disease (Redfield) and Medicine (Ballou, Wright), Walter Reed Army Institute of Research, Washington, DC; Department of Cell Biology, Litton Bionetics Inc., Kensington, Maryland (Markham, Sarngadharan); Laboratories of Tumor Cell Biology (Salahuddin, Gallo) and Immunogenetics (Folks), National Institutes of Health, Bethesda, Maryland; Biotech Research Laboratories, Rockville, Maryland (Bodner). This study evaluated intrafamilial transmission of human T-cell lymphotropic virus type [II (HTLV-II) from AIDS or AIDS-related complex (ARC) patients to spouses. Seven cases of AIDS and ARC, all associated with HTLV-II infection, were documented in married males whose family members consented to medical evaluation. Five spouses had evidence of HTLV-III infection. Three of these five spouses also had clinical evidence of ARC. The remaining four spouses were clinically healthy. Eleven children (between 14 months and 13 years of age) were evaluated. Only one l4-month-old child had antibodies to HTLV-III. The authors conclude that these data support the opinion that close household contact with patients who have ARC or AIDS is not an efficient mechanism for virus transmission, while demonstrating that HTLV-III can be transmitted by heterosexual contact. Case reports of patients, spouses, and children were studied, and clinical examination and antibody testing were done. Among AIDS and ARC patients referred to Walter Reed Hospital from July 1983 to July 1984, seven married patients' wives agreed to medical evaluation and were included in this study. Eleven children from these households were also examined. 1) Populations: Heterosexuals (IA6), 2) Transmission: Sexual Activity (IIA), 3) Transmission: Casual Contact (IIF) 1A6-Red-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Harris, Carol, MD; Small, Catherine Butkus, MD; Klein, Robert S., MD; Friedland, Gerald H., MD; Moll, Bernice, PhD; Emeson, Eugene E., MD; Spigland, Ilya, MD; Steigbigel, Neal H., MD. Immunodeficiency in Female Sexual Partners of Men with the Acquired Immunodeficiency Syndrome. The New England Journal of Medicine, 19 May 1983, Vol. 308, No. 20: 1181-1184. Division of Infectious Diseases, Department of Medicine, and the Divisions of Immunopathology and Virology, Department of Pathology, Montefiore Medical Center, the Bronx; the Department of Medicine, North Central Bronx Hospital; and the Departments of Medicine and Pathology, Albert Einstein College of Medicine, the Bronx, New York. To investigate heterosexual transmission of AIDS from men to women, seven female sexual partners of male drug abusers with AIDS were stud- ied. One of the seven women was found to have the full-blown syndrome, a second had an illness consistent with the prodrome of AIDS, including generalized lymphadenopathy, a decrease in the number of lymphocytes in her blood, and a decreased helper/suppressor T-cell ratio. All but one woman had at least one of these three conditions. All seven women denied the use of intravenous drugs or inhalants (cocaine or nitrites) and claimed that they had had sexual relations only with their partners (the male AIDS patients) throughout their relationship. Four of the subjects occasionally engaged in anal intercourse, while this was specifically denied by the other three. These findings suggest that AIDS may be transmitted between heterosexual men and women. The subjects were interviewed in detail by the investigators, with special attention to sexual practices and drug use. In addition, each subject was given a physical examination. Standard techniques were used to determine absolute lymphocyte counts and to test for syphilis. Immunologic and viral studies were also performed. Subjects were seven female sexual partners of male patients with AIDS in Bronx, New York. The women were not intravenous drug users and denied having any other sexual partners during the relationship. 1) Populations: Heterosexuals (IA6), 2) Transmission: Sexual Activity (ITA) 1A6-Har-8 [. Prevalence and Spread of AIDS/HTLV-III/LAV A. Population Studies and Groups at Risk 7. Other Se Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Desmyter, Jan, MD, PhD; Reynders, Martin, MT; Goubau, Patrick, MD. AIDS Virus Antibody in Polytransfused Dialysis Patients Vaccinated against Hepatitis B. British Medical Journal, 30 August 1986, Vol. 293: 537. Rega Institute and University Hospitals, University of Leuven, Leuven, Belgium. Patients receiving long-term hemodialysis are at increased risk of hepatitis B infection. Since hepatitis B virus and the AIDS virus have similar routes of transmission, this study tested patients who had been dialysed and had received at least 3 doses of hepatitis B vaccine in centers in Belgium for seroprevalence of lymphadenopathy-associated virus/human T-cell lymphotropic virus type III (LAV/HTLV-III) antibody. Although 17 of 729 patients were repeatedly reactive by enzyme-linked immunosorbent assay (ELISA), none was positive by any of four confirma- tory assays. Most false-positive results could be explained by cross- reactivity in the Abbott screening assay of antibody against lymphocyte components elicited by transfusion. The authors conclude that these findings for polyvaccinated, polytransfused patients show the complete safety from AIDS of all hepatitis B vaccines sold in Europe, regardless of method of manufacture, and that blood transfusion in Belgium has remained safe. Each of the patients was screened for LAV/HTLV-III antibody by the Abbott ELISA test, and positive results were confirmed by immunofluor- escence, Western blot, the Wellcome competitive ELISA, and a new competitive confirmatory ELISA. At the end of 1985, serum samples were obtained from 729 patients receiving hemodialysis (46% men, 54% women). These patients had received from 3 to 9 (mean, 4.2) doses of plasma-derived hepatitis B vaccine. They had undergone dialysis in 18 centers in Belgium for an average of 37 months. Three different manufacturers' vaccines were used. About 90% of patients had received blood transfusions. 1) Populations: Hemodialysis Patients (IA7), 2) Transmission: Blood Products (IIC), 3) Transmission: Hepatitis B Vaccine (IIG), 4) Blood Product Safety: Seroprevalence (VB2), 5) Geographic Trends: Europe (Belgium) (IB4) 1A7-Des-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Human T-Lymphotropic Virus Type I[II/Lymphadenopathy-Associated Virus Antibody Prevalence in U.S. Military Recruit Applicants. Morbidity and Mortality Weekly Report, 4 July 1986, Vol. 35, No. 26: 421-425. Centers for Disease Control, Atlanta, Georgia. From October 1985 through March 1986, as part of the medical evaluation of persons volunteering for military service, the U.S. Department of Defense tested 308,076 applicants for serologic evidence of infection with human T-cell lymphotropic virus type III (HTLV-III). The mean prevalence of confirmed positive tests was 1.5 per 1,000 applicants. Antibody prevalence increased progressively with age, consistently throughout the country. The positive rate was higher in men of all ages than in women by a ratio of 3:1. Prevalence also varied by race: for the 237,586 whites, the rate was 0.9 per 1,000; for the 55,185 blacks, it was 3.9 per 1,000; and for the 15,305 others, it was 2.6 per 1,000. Positive prevalence rates were highest in the coastal regions of the country, other than New England. Rates were lowest in New England and in the inland regions. The highest rates were found in applicants from major urban areas and lowest in those from rural areas. Testing of all military applicants for the presence of antibodies to HTLV- [II was conducted from October 1985 through March 1986 by an enzyme- linked immunosorbent assay (ELISA) technique. All samples reactive in repeated ELISA tests were also tested by the Western blot method. Applicants who were confirmed to be HTLV-III antibody-positive were excluded from military service. A total of 308,076 armed services applicants, predominantly young adults in their late teens (54%) and early twenties (33% were 20 to 25 years old), were tested. The applicant group was 85% male and 15% female; 77% white, 18% black, and 5% of other racial groups. 1) Populations: Military Recruits (IA7), 2) Geographic Trends: U.S. (IBl) 1A7-Cen-2 Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Human T-Lymphotropic Virus Type IlI/Lymphadenopathy-Associated Virus Antibody Testing at Alternate Sites. Morbidity and Mortality Weekly Report, 2 May 1986, Vol. 35, No. 17: 284-287. Centers for Disease Control, Atlanta, Georgia. On 2 March 1985, an enzyme-linked immunosorbent assay (ELISA) test to detect antibodies to human T-cell lymphotropic virus type III (HTLV-II) was licensed by the U.S. Food and Drug Administration for screening blood and plasma donations. Since many individuals in high-risk groups might wish to have their blood tested for reasons other than donation, federal funds for alternate testing sites were made available. A primary goal was to protect the nation's blood supply by limiting the potential for donation of blood that contained antibodies despite negative test results (false-negative) while ensuring that individuals who needed testing at alternate sites would receive adequate counseling and referral for medical evaluation. Cooperative agreements between the Centers for Disease Control (CDC) and 55 state and local health departments began 26 April 1985, originally for a 90-day period; most were extended for an additional 90 days. Preliminary data were reported to the CDC in September 1985 and January 1986. A total of 17.3% of the individuals tested at alternative sites had repeatedly reactive ELISA tests. No relationship was noted between the number of AIDS cases reported in a particular project area and the number of tests performed. This study describes alternative testing site activities by state. Blood tests for HTLV-III antibodies were done by ELISA. An estimated 874 testing sites were established nationwide, and 79,100 persons were tested by late 1985. 1) Populations: General Population (IA7), 2) Blood Product Safety: Seroprevalence (VB2) 1A7-Cen-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Acquired Immunodeficiency Syndrome in Correctional Facilities: A Report of the National Institute of Justice and the American Correctional Association. Morbidity and Mortality Weekly Report, 28 March 1986, Vol. 35, No. 12: 195-199. Centers for Disease Control, Atlanta, Georgia. The National Institutes of Justice and the American Correctional Association jointly sponsored a report on the incidence of AIDS in correctional facilities that was based in part on a prison survey. A total of 766 AIDS cases meeting the Centers for Disease Control definition were recognized among inmates. Twenty-four state prison systems and the Federal Bureau of Prisons reported 455 cases, and 20 large jail systems reported another 311 cases. Of the 766 cases, 322 (42%) died while in custody, 265 (35%) were released from custody, and 199 (23%) remained in custody. Among state and federal systems, 80% of the systems accounted for only 5% of the total AIDS cases, while 4% of the systems contributed 72% of the cases. Among city and county jail systems, 69% accounted for only 5% of cases, while 6% accounted for 77% of the cases. The geographic distribution of cases is highly skewed, with over 70% of cases in the mid-Atlantic region. In jurisdictions with many AIDS cases, the majority seem to have occurred among persons with histories of intravenous drug abuse. Educational efforts are under way In many of these jail systems, and a few are now screening or planning to screen all inmates. Eight cases of AIDS were reported among current or former correctional staff. Seven of these eight had known risk factors for AIDS. None of these staff reported involvement in an incident with an inmate in which transmission of the AIDS virus might have occurred. This report was based in part on a survey questionnaire mailed to all 50 state correctional departments, the Federal Bureau of Prisons, and 37 large city and county jail systems. Responses were received from mid-November 1985 through early January 1986 from all 50 state correctional systems, as well as 37 large city and county jail systems and the Federal Bureau of Prisons. A total of 766 AIDS cases were reported. 1) Populations: Prison Inmates (IA7), 2) Information/Education: Risk Behaviors and Protection (VA2), 3) Populations: [.V. Drug Abusers (IA2), 4) Geographic Trends: U.S. (IB1) 1A7-Cen-4 Author(s): Title: Source: Institution: Findings: Method: Kuritsky, J.N.; Rastogi, S.C.; Faich, G.A.; Schorr, J.B.; Menitove, J.E.; Reilly, R.W.; Bove, J.R. Results of Nationwide Screening of Blood and Plasma for Antibodies to Human T-Cell Lymphotropic Virus, Type III. Transfusion, 1986, Vol. 26, No. 2: 205-207. Office of Epidemiology and Biostatistics, Center for Drugs and Biologics, Food and Drug Administration, Rockville, Maryland (Kuritsky, Rastogi, Faich); American Red Cross, Washington, DC (Schorr); Council of Community Blood Centers, Falls Church, Virginia (Menitove); American Blood Resources Association, Annapolis, Maryland (Reilly); American Association of Blood Banks, Arlington, Virginia (Bove). Screening results from blood and plasma collection centers varied over time and among human T-cell lymphotropic virus type II (HTLV-II) testing kits. Of 2,502,829 units from blood collection centers, 25,324 units (1.01%) were initially reactive and 8,443 units (0.34%) were repeatedly reactive. Abbott test kits were used to screen 87% of all units; 22,229 (1.02%) were initially reactive and 6,730 (0.31%) were repeatedly reactive. Electro-Nucleonics (ENI) test kits were used to screen 11% of the units, of which 2,657 (0.99%) were initially reactive and 1,561 (0.58%) were repeatedly reactive. Two percent of the units were screened with Litton test kits; 438 (0.78%) were initially reactive, and 152 of these (0.27%) were repeatedly reactive. During the surveil- lance period there appeared to be a trend toward an increase in the rate of repeatedly reactive units from centers using the Abbott test kit and a decrease in the rate of repeatedly reactive units tested with the ENI kit. Of units screened for which the sex of the donor was specified, the repeatedly reactive rate was 0.33% for women and 0.30% for men. Plasma screening showed 3,978 (0.15%) units were repeatedly reactive. Eighty-three percent of the plasma units were screened with ENI test kits, and 17% were screened with Abbott test kits. The repeatedly reactive rates by test kit used were 0.15% and 0.18%, respectively. Confirmation of testing with Western blot procedures suggests that drifts In reactivity rates are likely to be due to shifts in test kit performance rather than to changes in the prevalence of true positives. Nearly equal repeatedly reactive rates among men and women, even though 90% of adult AIDS patients are men, reflect the self-exclusion of high-risk men and high rates of false-positivity for both sexes. The authors note that because certain human leukocyte antigen antibodies may produce nonspecific results, false-positivity rates may vary by sex. From 22 April to 28 July and from 7 October to 3 November 1985, the American Red Cross, the Council of Community Blood Centers, the American Association of Blood Banks, and the American Blood Resources Association provided the Food and Drug Administration with systematic data, at two-week intervals, on HTLV-III test kit results at blood and plasma collection centers. The following data were collected from 120 to 153 centers: (1) number of blood units tested during the reporting 1A7-Kur-5 Sample Size: Policy Keys: interval, (2) number of initially reactive units, (3) number of repeatedly reactive units, (4) test kit manufacturer, and (5) sex of donor. A repeat- edly reactive unit was defined as one which was reactive on an initial test and also reactive on at least one of two subsequent enzyme-linked immunosorbent assays run on the original sample. During the surveillance period, 120 to 153 blood collection centers reported results for 2,502,829 units. Screening results were received for 2,603,652 units from plasma collection centers at 275 locations. About 70% of all blood units collected in the U.S. during this 18-week period are represented in these data. 1) Populations: Blood Donors (IA7), 2) Blood Product Safety: Screening Tests and Assays (VB1), 3) Seroprevalence: False-Positive Results (VB2) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Hanrahan, J.P.; Wormser, G.P.; Reilly, A.A.; Maguire, B.H.; Gavis, G.; Morse, D.L. Prolonged Incubation Period of AIDS in Intravenous Drug Abusers: Epidemiological Evidence in Prison Inmates. The Journal of Infectious Diseases, August 1984, Vol. 150, No. 2: 263- 266. Division of Field Services, Centers for Disease Control, Atlanta, Georgia; Division of Infectious Disease, Department of Medicine, New York Medical College, Valhalla, New York; and New York State Departments of Health and Correctional Services, Albany, New York. Fourteen New York State prison inmates who developed AIDS while incarcerated were studied to estimate the incubation period of AIDS in intravenous ([.V.) drug abusers. Study subjects developed AIDS an average of 22.6 months (range, 4 to 36 months) after imprisonment. All 14 had regularly used illicit drugs [.V. in New York City prior to imprisonment. Only one reported having used drugs while in prison. All 14 were heterosexual prior to imprisonment, and only 2 reported homosexual contact while incarcerated. Leukocyte counts of these Inmates upon admission to the prison, when they were healthy, were depressed by one-third compared with those in fellow inmates who served as matched control subjects. The mean interval of 22.6 months is a minimum estimate of the incubation period for AIDS in these inmates. This assumes, without basis, that transmission occurred close to the time of incarceration. Actual incubation periods, in fact, may be longer. Nevertheless, it is remarkably consistent with the 22.7 month mean incubation period reported for transfusion-related cases in another study by Auerbach et al., 1984). In this retrospective clinical study of inmates with AIDS, subjects were interviewed by health care personnel and questioned about [.V. drug use and homosexual contact before and during imprisonment. Information was available from the inmates' time of entering from a medical review, physical examination, and laboratory evaluation performed by the New York State Correctional System. These tests included a total leukocyte count. Fourteen of 18 heterosexual inmates in New York state correctional facilities who had developed AIDS between November 1981 and January 1983 were studied. The l4 inmates ranged in age from 24 to 42 years (mean, 31). Five were black, four were white, and five were Hispanic. A control group (total, 42) of other inmates included three inmates matched to each AIDS victim by age (within 3 years), sex, race, date of entry into the state correctional system (within 2 weeks), and prior history of I.V. drug use. 1) Populations: Prison Inmates (IA7), 2) Incubation Period (IIIC), 3) Transmission: [.V. Drug Abuse (IIB), 4) Immunological Aspects (IIE) 1A7-Han-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Wormser, Gary P., MD; Krupp, Lauren B., MD; Hanrahan, John P., MD; Gavis, Gustave, MD; Spira, Thomas IJ., MD; Cunningham-Rundles, Susanna, PhD. Acquired Immunodeficiency Syndrome in Male Prisoners: New Insights into an Emerging Syndrome. Annals of Internal Medicine, March 1983, Vol. 98, No. 3: 297-303. Division of Infectious Diseases and the Department of Medicine of Westchester County Medical Center, and New York Medical College, Valhalla, New York; Field Services Division, Epidemiology Program Office, Centers for Disease Control, New York State Department of Health, and New York State Department of Correctional Services, Albany, New York; Clinical Immunology Laboratory, Division of Host Factors, Centers for Disease Control, Atlanta, Georgia; Memorial Sloan- Kettering Cancer Center, New York, New York. Between September 1981 and June 1982, AIDS and Pneumocystis carinii pneumonia were diagnosed in seven previously healthy young men incarcerated for 5 to 38 months in New York State prisons. None of the inmates were homosexual, but all had used intravenous (I.V.) drugs extensively before incarceration. All seven patients were anergic (had decreased skin reactivity to antigens), six were lymphopenic (had decreased numbers of lymphocytes), and all developed oral candidiasis. Profound defects were observed in helper/suppressor T-cell ratios, and no underlying immunosuppressive disorder was found. Based on these cases, the incidence of AIDS among inmates of New York prisons was estimated to be at least 20 per 100,000 population. Study findings suggest that inmates, particularly those with a history of L.V. drug use, may be at substantial risk for developing AIDS and that discontinuation of regular I.V. drug use will not necessarily prevent the emergence or progression of this syndrome. These observations have important implications for the diagnosis and treatment of inmates in the prison health care system. This study presents case reports of seven patients, including medical record review and autopsy findings (where pertinent). Diagnosis of P. carinii pneumonia was established by the finding of P. carinii with methenamine silver or Giemsa stains in lung biopsy specimens. Autopsy records of all New York State prisoners (not including New York City or federal prisoners) who died between January 1977 and October 1981 were reviewed for evidence of P. carinii pneumonia or unexplained respiratory death. A group of seven previously healthy young men incarcerated in New York State prisons for 5 to 38 months were studied. Their ages ranged from 25 to 38 years (mean, 29.3); three were white, two Hispanic, and two black. All were intravenous drug abusers, and the mean duration of their drug abuse was 12.2 years. 1A7-Wor-7 Policy Keys: 1) Populations: Prison Inmates (IA7), 2) Transmission: I.V. Drug Abuse (IIB) [. Prevalence and Spread of AIDS/HTLV-III/LAV B. Geographic and Regional Trends I. U.S. and Canada Author(s): Title: Source: [nstitution: Findings: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Acquired Immunodeficiency Syndrome (AIDS) in Western Palm Beach County, Florida. Morbidity and Mortality Weekly Report, 3 October 1986, Vol. 35, No. 39: 609-613. Centers for Disease Control, Atlanta, Georgia. From July 1982 through 15 September 1986, 79 persons meeting the surveillance case definition for AIDS were reported from western Palm Beach County, Florida. These patients were residents of the towns of Belle Glade (62 cases), Pahokee (7 cases), and South Bay (10 cases) at the time of onset of their illness. Based on 1980 census data, the calculated cumulative incidence for AIDS in these three towns is 295 per 100,000 population, compared with 10.8 per 100,000 population in the U.S. as a whole. Of these 79, 64 were male, and all but 3 were older than 13 years. The three pediatric cases were apparently infected perinatally. Risk factors were undetermined for 13 (11 men, 2 women), 10 of whom died before epidemiologic investigations could be completed. Known risk groups included homosexuals and bisexuals (10 men), heterosexual intravenous (I.V.) drug abusers (18 men, 6 women), transfusion recipients (2 women), heterosexual contacts of individuals with AIDS or at increased risk for AIDS, or heterosexual Haitians (24 men, 3 women), and children born to mothers positive for human T-cell lymphotropic virus type IlI/lymphadenopathy-associated virus (HTLV-III/LAV) antibodies (1 boy, 2 girls). Sixty-two of the cases were from an area in Belle Glade characterized by high rates of [.V. drug abuse and sexually transmitted diseases. Investigations in May 1985, May 1986, and August 1986 revealed that 19 adult AIDS cases in Belle Glade could be directly linked to at least one other reported AIDS case by sexual contact, I.V. needle sharing, or both. Five of the 10 adult women with AIDS reported between February 1982 and August 1986 were prostitutes; four of these five were also LV. drug abusers. To evaluate the prevalence of and risk factors for HTLV-III/LAV infection in Belle Glade, a communitywide study was conducted from February through September 1986 to interview and determine seropreva- lence rates for persons in this area. Preliminary results of this study indicate that 30 of 959 (3.1%) persons tested had detectable antibodies to HTLV-III/LAV by both enzyme immunoassay and Western blot methods. Sex-, age-, and race-specific rates were available for 736 subjects: 14 of 378 (3.7%) males, 12 of 358 (3.4%) females, 0 of 121 children aged 2 to 10 years, and 26 of 616 (4.2%) black non-Hispanic persons (including 13 of 150 [8.7%] persons born in Haiti, 0 of 42 Hispanic persons, and 0 of 60 white non-Hispanic persons) were seropositive. Arthropods have been hypothesized (and subsequently dismissed) as a mode of HTLV-III/LAV transmission in Belle Glade. As a measure of exposure to different mosquito vectors and antibody prevalence, samples 1B1-Cen-1 Method: Sample Size: Policy Keys: were tested for antibodies to five insect-transmitted viruses prevalent in South Florida and the Caribbean. No significant difference in prevalence of antibodies to these insect-transmitted viruses was found between HTLV-III/LAV-infected and noninfected persons. This study reports surveillance of AIDS cases reported in western Palm Beach County, Florida. In addition, a community-wide seroprevalence study was conducted by the Florida Department of Health and Rehabili- tative Services and the Centers for Disease Control. A proportionate- sampling scheme was used to interview and test persons living in and around the neighborhoods in which most of the AIDS patients lived. Blood samples were tested for antibodies to HTLV-II[/LAV by enzyme immunoassay and Western blot methods. Samples obtained during the survey were also tested for antibodies to five arboviruses (Tensaw, Magauri, Keystone, St. Louis encephalitis, and dengue-2) prevalent in South Florida and the Caribbean. Surveillance data for 79 AIDS patients from western Palm Beach County (62 from Belle Glade, 7 from Pahokee, and 10 from South Bay) were reviewed. In addition, 959 persons in Belle Glade were interviewed and tested in the serological survey. 1) Geographic Trends: U.S. (IBl), 2) Populations: Minorities (IA5), 3) Transmission: Arthropods (IIG) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Elmslie, Kim. AIDS Surveillance in Canada. Canadian Medical Association Journal, 1 October 1986, Vol. 135: 780. National Aides Centre, Laboratory Centre for Disease Control, Ottawa, Ontario, Canada. As of 14 July 1986, 638 cases of AIDS meeting the Centers for Disease Control (CDC) definition had been reported to the AIDS surveillance program in Ottawa, Canada. Of the total, 92% were reported from British Columbia, Ontario, and Quebec provinces, where Canada's urban populations are concentrated. Homosexual or bisexual men comprise 81% of the cases. Of these, 4% also reported the use of intravenous drugs. The remaining 19% were classified as follows: 8.5% were born in areas where AIDS is prevalent, such as Haiti and central Africa; 2.2% were children of high-risk parents; 2.0% were blood transfusion recipients; 1.4% were blood product recipients; 0.3% were intravenous drug abusers; and 2.5% had no know risk factor. Of the 638 cases, 94% were in males (588 adults and 10 children). Only 33 adults and 7 children were female. Approximately 90% of the patients were aged 20 to 49 years at the time of diagnosis. The overall case fatality rate has been 50% as of October 1986. As in other areas, the number of cases has been increasing geometrically year by year, with almost twice as many cases reported in 1985 as in 1984. This report provides a summary of AIDS surveillance in Canada. The demographic details of 638 cases of AIDS in Canada are presented. 1) Geographic Trends: Canada (IB1) 1B1-Elm-2 Author(s): Title: Source: Institution: Findings: Morgan, W. Meade, PhD; Curran, James W., MD, MPH. Acquired Immunodeficiency Syndrome: Current and Future Trends. Public Health Reports, September-October 1986, Vol. 101, No. 5: 459- 465. Statistics and Data Management Branch, AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. To project the number and the distribution of AIDS cases through 1991, trends among cases reported to the Centers for Disease Control (CDC) were analyzed and empirical models were employed. Between | June 1981 and 19 May 1986, the number of cases has increased steadily, but the doubling times continue to lengthen, indicating that the rate of increase is not exponential. It is projected that 15,800 new AIDS cases will be diagnosed in 1986, 23,000 in 1987, 33,000 in 1988, 45,000 in 1989, 58,000 in 1990, and 74,000 in 1991. The most significant trend by patient group has been a decline in the proportion of AIDS patients born outside the United States, in Haiti or central African countries. If current trends continue, this group will account for 1.3% of cases diagnosed in 1986 and only 0.3% in 1991. The proportion of diagnosed cases associated with blood transfusions and in hemophiliacs has increased slightly, but all of these represent infection before routine human T-cell lymphotropic virus type III/lymphadeno- pathy-associated virus (HTLV-III/LAV) antibody testing of donors began in the spring of 1985. The empirical model projects that 2.0% of adult AIDS cases in 1986 will be due to transfusion of blood or blood compon- ents and that this will increase to 2.5% in 1991. The proportion of cases in the heterosexual-contact risk group also has increased from 1983 to 1986. If current trends continue, the proportion of heterosexual-contact cases is projected to be 2.0% in 1986, increasing to 5.0% in 1991. The geographic distribution of diagnosed adult AIDS cases has changed markedly from 1983 to 1986. The proportion of diagnosed homosexual cases outside New York City and San Francisco has increased from 50% before 1984 to 65% after 1984. The geographic distribution of cases among heterosexual intravenous (I.V.) drug abusers has changed less. By 1991, only 12% of total cases are projected to be diagnosed in New York City and 8% in San Francisco, which together had reported more than half of the cases from 1981 to 1983. The distribution of cases by race in adults did not change significantly from 1983 to 1986, and there has been a marginally significant increase in the proportion of women with AIDS. There has also been a small but significant increase in the age of patients, from a mean of 36.3 years before 1984 to 37.8 years after 1984. The relative distribution of reported adult and pediatric cases has not changed significantly over time. It is projected that 1.4% (200) of 1986 cases will occur in children under 13 years of age, decreasing slightly to 1.2% (1,000) of cases in 1991. 1B1-Mor-3 Method: Sample Size: Policy Keys: The authors point out that these projections are conservative since they are based only on cases reported to the CDC. A review of death certificates in four metropolitan areas suggested that an additional 10% of diagnosed cases of AIDS are not reported to the CDC. At least another 10% of patients may be seriously ill with HTLV-III/LAV infections which do not fit current surveillance and reporting criteria. The empirical models do not consider the availability of therapy or vaccine, preventable cofactors, or the effectiveness of primary prevention efforts. The models used to project the number and distribution of AIDS cases by patient group, geographic area of residence, gender, race, and age were empirically based reflecting observed trends in the distribution of reported cases and assuming that these trends would continue unchanged over time. The projections involved a two-stage process. First, the number of cases reported each month was adjusted to obtain estimates of the cases actually diagnosed during that month. Second, a quadratic polynomial was fitted and the resulting model was projected to 1991. To obtain estimates for the number of AIDS-associated deaths, survival times were calculated from surveillance data by using the Kaplan-Meier method for life table analysis. The median survival time was estimated as 12 months and the cumulative 3-year survival as 28%. [t was assumed that the cumulative survival times follow a negative exponential distribution, with 50% of patients living at most | year and only 12% surviving for more than 3 years. Not applicable. 1) Geographic Trends: U.S. (Future Incidence) (IBl), 2) Related Policy Issues (VI) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kristal, Alan R., DrPH. The Impact of the Acquired Immunodeficiency Syndrome on Patterns of Premature Death in New York City. Journal of the American Medical Association, 2 May 1986, Vol. 255, No. 17: 2306-2310. Office of Epidemiologic Surveillance and Statistics, New York City Department of Health,New York. This study examined the impact of AIDS on patterns of mortality among persons 15 to 64 years old in New York City. In 1984, the AIDS mortality rate per 100,000 persons aged 15 to 64 years was 42.2 for males and 5.3 for females. AIDS was among the five leading causes of death for males aged 25 to 54 years, the fourth leading cause of death for women aged 25 to 29 years, and the second leading cause of death for women aged 30 to 34 years. Years of potential life lost for males aged 15 to 64 years due to AIDS was almost 10% and for females, 3.6%. Blacks and Hispanics had higher mortality rates than Asians or whites for both men and women in the highest-risk age group, 20 to 44 years. Higher mortality in blacks and Hispanics is believed to be related to a higher prevalence of drug abuse in these populations and not to ethnicity per se. Study findings document large increases in early death attributable to AIDS. The New York City AIDS surveillance registry was matched to the New York vital statistics registry to identify deaths caused by AIDS. ICD-9 codes were used as a diagnostic classification scheme to identify AIDS- related deaths. AIDS deaths, mortality rates and proportional mortality, causes of death, and years of potential life lost were calculated. A total of 1,799 deaths in New York City were attributed to AIDS between 1980 and 1984. More than 86% of these deaths could be matched to the AIDS surveillance registry, and 74% were coded as actually being AIDS deaths by ICD-9 279.1. 1) Geographic Trends: U.S. (IB1), 2) Disease Stages (IIIC) 1B1-Kri-4 Author(s): Title: Source: Institution: Findings: Method: Goedert, James J.; Biggar, Robert J.; Weiss, Stanley H.; Eyster, M. Elaine; Melbye, Mads; Wilson, Susan; Ginzburg, Harold M.; Grossman, Ronald J.; DiGioia, Richard A.; Sanchez, William C.; Giron, Jose A.; Ebbesen, Peter; Gallo, Robert C.; Blattner, William A. Three-Year Incidence of AIDS in Five Cohorts of HTLV-III-Infected Risk Group Members. Science, 28 February 1986, Vol. 231, No. 4741: 992-995. Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland (Goedert, Biggar, Weiss, Blattner); Milton S. Hershey Medical Center of the Pennsylvania State University, Hershey, Pennsylvania (Eyster); Institute of Cancer Research, Radium Stationen, Aarhus, Denmark (Melbye, Ebbesen); ORI, Inc., Bethesda, Maryland (Wilson); National Institute on Drug Abuse, Rockville, Maryland (Ginzburg); Medical Arts Center Hospital, New York, New York (Grossman); Department of Medicine, George Washington University Hospital, Washington, DC (DiGioia); Department of Medicine, Flushing Hospital, New York, New York (Giron); Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Gallo). To assess the long-term prognosis of human T-cell lymphotropic virus type III (HTLV-II) infection, the incidence rate of AIDS among persons infected with HTLV-II was evaluated prospectively among 725 persons who were at high risk for AIDS and had enrolled before October 1982 in cohort studies of homosexual men, intravenous (I.V.) drug users, and hemophiliacs. A total of 276 (38.1%) of the subjects were either HTLV- [II antibody positive at enrollment or developed antibodies subsequently. All subjects were apparently free of AIDS at enrollment, but AIDS had developed in 28 (10.1%) of the antibody-positive subjects before August 1985. The 3-year incidence rate of AIDS among HTLV-II antibody- positive subjects was 34.2% in the cohort of homosexual men in Manhattan and between 8.0% and 17.2% in the four other cohorts (calculated after accounting for uncertainty about the time of conversion and loss to follow-up of a few subjects). Five hemophiliacs who were followed after becoming antibody positive developed AIDS 2 to 5 years (28 to 62 months) after the estimated date of seroconversion. Five cohorts of high-risk persons in Manhattan, Washington (D.C.), Hershey (Pa.), Queens (N.Y.), and Denmark were studied prospectively. Serum samples were tested for HTLV-II antibodies by an enzyme-linked immunosorbent assay. The Manhattan and Washington cohorts were followed up on an annual basis between May 1982 and June 1985, and follow-up was 92% complete. Subjects in the Denmark cohort were initially seen in December 1981, with follow-up sessions in April 1982, February 1983, and September 1984; follow-up was 82% complete. Hershey subjects were hemophilia A patients receiving comprehensive care as of September 1982 with semiannual or annual clinic visits, which were 100% complete. The Queens cohort consisted of [.V. drug users 1B1-Goe-5 Sample Size: Policy Keys: enrolled in late 1981 and followed up in early 1985, at which time follow- up was 29% complete. The five cohorts totaled 725 persons, consisting of homosexual men in Manhattan, New York; homosexual men in Washington, D.C.; homosexual men in Copenhagen and Aarhus, Denmark; hemophilia A patients in Hershey, Pennsylvania; and I.V. drug users in Queens, New York. 1) Geographic Trends: U.S. (IBl), 2) Populations: Homosexuals, I.V. Drug Users, Hemophiliacs (IA1,2,3), 3) Incubation Period and Disease Stages (I1IC) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Brunet, J.B., MD; Ancelle, R.A., MD. The International Occurrence of the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, November 1985, Vol. 103, No. 5: 670-674. WHO Collaborating Centre on AIDS, Institut de Medecine et d'Epidemiologie Tropicales, Hopital Claude Bernard, Paris, France. Through December 1984, 9,932 cases of AIDS had been reported, mainly from North and South America and Europe; 85% of these cases occurred in the U.S. Haiti and the U.S. have the highest reported incidence rates, 59 and 36 per 1,000,000 population, respectively. Six-month incidence rates in the U.S. ranged from 0.3 per million in the beginning of 1981 to 10.4 by the end of 1984. Brazil, Canada, Denmark, Switzerland, France, West Germany, the United Kingdom, and the Netherlands show a slower increase. Homosexual men and intravenous drug users are still the main risk groups in the U.S. and Europe. The disease is prevalent in heterosexual Haitians and Africans, whether they live in their native countries or abroad. Cases of the syndrome have been identified in Zaire, Rwanda, Zambia, and Uganda, but its full extent is not yet known. Consistent with the general history of epidemics, the appearance of geographically separated sites of incidence could be linked to population migrations; however, no evidence has been found to identify an index location. This report provides a review of the literature and a summary of surveillance data obtained from the Pan American Health Organization, the World Health Organization, the U.S. Centers for Disease Control, and the Laboratory Centre for Disease Control in Canada. The 9,932 cases of AIDS reported worldwide as of December 1984 are included. 1) Geographic Trends: U.S., Haiti, Africa, Europe (IBl,2,4,5), 2) Populations: Homosexuals, [.V. Drug Abusers, Heterosexuals (IA1,2,6) 1B1-Bru-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Moss, A.R.; Bacchetti, P.; Osmond, D.; Dritz, S.; Abrams, D.; Conant, M.; Volberding, P.; Ziegler, J. Incidence of the Acquired Immunodeficiency Syndrome in San Francisco, 1980-1983. The Journal of Infectious Diseases, July 1985, Vol. 152, No. Ll: 152-161. Departments of Epidemiology and Medicine, University of California, San Francisco; Bureau of Communicable Disease Control, San Francisco Department of Public Health, San Francisco, California. The incidence of AIDS among San Francisco residents rose steadily from the last quarter of 1980, when the first case was identified, through the last quarter of 1983. New cases were diagnosed at a rate of 25 per month in the last quarter of 1983. The incidence appeared to decline in mid-1983, but this is thought to be a case-finding artifact. About 99% of San Francisco AIDS patients were homosexual or bisexual men. The cumulative incidence rate among homosexual and bisexual men was estimated to be 770 cases per 100,000 in the last quarter of 1983. The incidence rate of AIDS increased with age, and the increase was greater than that found with other sexually transmitted diseases. The difference in the age distributions between cases of AIDS and syphilis suggests either that susceptibility to AIDS increases with age or that the average latency associated with AIDS is longer than previously thought. San Francisco AIDS incidence data from active local-agency surveillance of larger hospitals and passive surveillance of small hospitals are presented by area of the city; marital status; quarter of diagnosis; incidence of Kaposi's sarcoma, opportunistic infections, and both; incidence of intravenous drug abuse; and age group comparisons for cases of reported syphilis and amebiasis. Incidence rates were calculated by dividing number of cases by population denominators from 1980 census data. Best-fitting quadratic and exponential curves were obtained by using weighted least squares. A cumulative total of 370 San Francisco AIDS cases are reported, those meeting Centers for Disease Control criteria through the end of 1983; of these, 215 were diagnosed and reported before | July 1983, and 104 were diagnosed and reported before | January 1983. 1) Geographic Trends: U.S. (San Francisco) (IBl), 2) Populations: Homosexuals (IA 1), 3) Incubation Period (IIIC) 1B1-Mos-7 Author(s): Title: Source: Institution: Findings: Method: Hardy, Ann M., DrPH; Allen, James R., MD, MPH; Morgan, W. Meade, PhD; Curran, James W., MD, MPH. The Incidence Rate of Acquired Immunodeficiency Syndrome in Selected Populations. Journal of the American Medical Association, 11 January 1985, Vol. 253, No. 2: 215-220. Surveillance Section, AIDS Activity, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. White single men had the highest incidence rate of AIDS in all four U.S. geographic areas; the rates in all other racial and ethnic groups were extremely low. Single men overall in San Francisco and the borough of Manhattan had rates four to five times higher than those in Los Angeles and in other boroughs of New York City. The incidence rates for all intravenous ([.V.) drug users was 113.3 per 100,000 population, more than 12 times the national rate for single men (8.9 per 100,000); rates for I.V. drug users in New York City and New Jersey were two to three times higher than for the rest of the U.S. Incidence rates for Haitians arriving since 1978 were much higher than for earlier entrants or for the U.S. population in general, with the rate for Haitians in Miami more than four times that in New York City and the rest of the country. The incidence rate of AIDS in persons with hemophilia A was six times higher than in persons with hemophilia B, and much higher in those with severe hemophilia A than in moderate or mild cases. The estimated incidence rate for female sex contacts of male I.V. drug users was low (3.1 per 100,000) compared with other patient groups, but the rates for these groups in New York City and New Jersey were 30 times higher than for the rest of the U.S. Incidence rates for patients who had had blood transfusions in the last 6 years were also low, although children in this group had higher rates than adults. Rates for both subgroups for those receiving 10 or more units of blood were 27 to 32 times higher than for recipients of fewer than 10 units. The incidence rate of AIDS in certain of these groups is similar to population mortality rates for heart disease and cancer, two leading causes of death, and higher than the mortality rate for motor vehicle accidents. In this epidemiological study, definite AIDS cases diagnosed between | June 1983 and 31 May 1984 were grouped as described below. A 3-month Centers for Disease Control (CDC) reporting lag was allowed as the historical mean time lag. Data about these patients' risk factors for AIDS, race, sex, geographic location, and date of entry for immigrants were obtained from confidential surveillance reports. Geographic classifications were residence at onset of illness; patients having more than one risk factor were included in both groups; men of unknown marital status and immigrants (Haitians) of unknown entry date were allocated to subgroups in proportion to the number of others in those groups. Best denominator estimates of the total population for each group were obtained from 1980 census data and other sources; midpoints were used when only a range was given. Incidence rates were calculated by dividing number of cases by population. 1Bl1-Har-8 Sample Size: Policy Keys: The sample consisted of definite AIDS cases diagnosed in the U.S. between | June 1983 and 31 May 1984 and reported to the CDC by 31 August 1984: 3,096 total U.S. victims over age 5; 2,220 single men 15 years or older; 850 I.V. drug users; 94 Haitian entrants; 24 hemophiliacs; 13 female sex contacts of male I.V. drug users; and 50 persons receiving blood transfusions. Single men aged 15 and older were grouped by residence at onset (Manhattan, San Francisco, other U.S.); I.V. drug users were also grouped by residence at onset (New York City, New Jersey, other U.S.); Haitian entrants were grouped by entry before 1978 and since 1 January 1978, and by residence (New York City, Miami, other U.S.); hemophiliacs were grouped by types A and B (and type A by severity); female sex contacts of male [.V. drug users were grouped by residence (New York City, New Jersey, other U.S.); and blood transfusion recipients were grouped as adult and pediatric patients (recipients who were younger than | year and those 21 years of age and older) and were further divided into those receiving fewer than 10 units of blood and those receiving 10 or more units. 1) Geographic Trends: U.S. (IBl), 2) Populations: Homosexuals, [.V. Drug Users, Hemophiliacs, Pediatric Cases, Haitians, Heterosexuals (IA1,2,3,4,5,6) Author(s): Title: Source: Institution: Findings: Methods: Sample Size: Goedert, James J.; Biggar, Robert J.; Winn, Deborah M.; Mann, Dean L.; Byar, David P.; Strong, Douglas M.; DiGioia, Richard A.; Grossman, Ronald J.; Sanchez, William C.; Kase, Ronald G.; Greene, Mark H.; Hoover, Robert N.; Blattner, William A. Decreased Helper T Lymphocytes in Homosexual Men: I. Sexual Contact in High-Incidence Areas for the Acquired Immunodeficiency Syndrome. American Journal of Epidemiology, 1985, Vol. 121, No. 5: 629-636. Environmental Epidemiology Branch (Goedert, Biggar, Winn, Kase, Greene, Hoover, Blattner), Laboratory of Human Carcinogenesis (Mann), and Biometry Branch (Byar), Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland (Strong). In this study the correlation between homosexual contact with men from high-risk areas and a higher rate of immunologic abnormality was examined. Helper T-cell counts, indicative of immune status, in New York City and Washington, D.C., homosexual men who had sexual contact with men from areas where AIDS is endemic (such as San Francisco) were found to be much lower than in Washington homosexuals who did not have such sexual contacts. Helper T-cell counts in the Washington men were inversely correlated with a greater number of endemic-area sexual partners, even after adjusting for multiple confounding patient characteristics. These data suggest that deficits of helper T cells can be acquired by homosexual contact with men in cities where AIDS is common, supporting the theory that low helper T-cell counts are caused by a sexually transmitted agent. The authors suggest that frequent homosexual exposure to residents from high-risk areas may increase the risk of acquiring AIDS. Comparisons were made of homosexual men having sexual contacts with persons from high-risk areas (San Francisco, New York, Los Angeles) and homosexual men without such contacts. Patients who agreed to participate completed a self-administered questionnaire concerning medical conditions, drug use, and sexual practices. All subjects were given physical exams by one of two physicians, including blood samples for white blood cell count and for OKT4 and OKT8 antibody tests as measures of helper and suppressor T-cell counts. Descriptive and multivariate statistical analyses were performed. A total of 245 homosexual men were recruited from the patient popula- tion of a private physician in New York City from May to June 1982 (85 patients), and two private physicians in Washington, D.C. (160 patients). The New York City group had an average age of 36 years, was 91% white, averaged 78 homosexual partners in the previous year, and averaged 59 days of nitrite inhalant use in the previous year. Among the Washington group, 96 men (60%) reported at least one sexual contact between January 1980 and June 1982 with men in one of three high-risk cities (New York, San Francisco, and Los Angeles). This "exposed" group 1B1-Goe-9 Policy Keys: of D.C. men had a mean age of 33 years, was 80% white, averaged 42 homosexual partners in the previous year, and averaged 42 days of nitrite inhalant use in the previous year. The Washington "unexposed" group of 64 men (40%) had a median age of 34 years, was 78% white, averaged 26 homosexual partners in the previous year, and averaged 24 days of nitrite inhalant use in the previous year. 1) Geographic Trends: U.S. (IBl), 2) Populations: Homosexuals (IAl), 3) Cofactors: Demographic Status (IC1), 4) Transmission: Sexual Activity (IIA) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kalyanaraman, V.S.; Cabradilla, C.D.; Getchell, J.P.; Narayanan, R.; Braff, E.H.; Chermann, J.-C.; Barre-Sinoussi, F.; Montagnier, L.; Kaplan, J.; Spira, T.J.; Fishbein, D.; Jaife, H.W.; Curran, J.W.; Francis, D.P. Antibodies to the Core Protein of Lymphadenopathy-Associated Virus (LAV) in Patients with AIDS. Science, 20 July 1984, Vol. 225: 321-323. Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Kalyanaraman, Cabradilla, Getchell, Narayanan, Spira, Kaplan, Fishbein, Jaffe, Curran, Francis); San Francisco City Clinic, San Francisco, California (Braff); Departement de Virologie, Institut Pasteur, Paris, France (Chermann, Barre-Sinoussi, Montagnier). Lymphadenopathy-associated virus (LAV), a human T-lymphotropic retrovirus isolated from homosexual men with lymphadenopathy, has been causally associated with AIDS. Antibody to LAV protein 25 (p25) (the major core protein of LAV) was found in the blood serum of 51 of 125 AIDS patients, 81 of 113 patients with lymphadenopathy syndrome (LAS), none of 70 workers at the Centers for Disease Control (CDC) (some of whom had handled specimens from AIDS patients), and none of 189 random blood donors. Of 100 homosexual men from San Francisco from whom serum samples were obtained in 1978, only | had antibody to LAV p25; in contrast, of 50 homosexual men in the same community whose serum was obtained in 1984, 12 had antibodies to LAV p25. Results show that a high proportion of serum samples from patients with AIDS and LAS and from people at risk for AIDS have detectible antibodies to p25 of LAV. These antibodies also react specifically with LAV p25. The presence of the antibody to LAV p25 in only 42% of the serum samples from AIDS patients may be due to the fact that (1) these patients are highly immunosuppressed or (2) more than one virus is involved in AIDS. Since antibodies to LAV p25 were also found in apparently healthy homosexuals, the results of the study have to be interpreted cautiously; other cofactors in addition to viruses may be involved in the causation of AIDS. In this seroepidemiological study, a specific radioimmunoprecipitation test was developed to detect antibodies to LAV p25. Along with this test, these investigators used similar antibodies to core protein p24 of human T-cell lymphotropic virus types [ and II to determine which antibodies were prevalent in the study groups of homosexual men with AIDS and lymphadenopathy syndrome. The sample included 125 AIDS patients, [13 patients with lymphadenopathy syndrome, 70 workers from the CDC, 189 random blood donors, and 100 homosexual men from San Francisco. 1) Geographic Trends: U.S. (IBl), 2) Populations: Homosexuals, Health Care Workers, Blood Donors (IA1,7) 1B1-Kal-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Selik, Richard M., MD; Haverkos, Harry W., MD; Curran, James W., MD, MPH. Acquired Immune Deficiency Syndrome (AIDS) Trends in the United States, 1978-1982. The American Journal of Medicine, March 1984, Vol. 76: 493-500. AIDS Activity, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. This is a summary of surveillance for AIDS conducted by the Centers for Disease Control (CDC) through the first quarter of 1983. The 1,299 reported cases showed trends of increasing incidence among all risk groups: homosexual men (72% of all cases), intravenous (I.V.) drug abusers (17%), persons of Haitian origin (5%), persons with hemophilia (1%), and others (6%). More than two-thirds of cases diagnosed in 1982 and the first quarter of 1983 were reported among residents of 35 states and the District of Columbia. The majority were from New York (47%) and California (22%). This overall distribution is parallel to that of the cases in homosexual and bisexual men, which constitute 72% of the total. In contrast, the geographic limitation of the majority of cases among [.V. drug abusers to New York and New Jersey is striking; fewer than 5% resided in California, despite a large number of cases reported in homosexual men from this state. Of the 6% of patients without well- established risk factors for AIDS, many have suspected risk factors, such as blood transfusion or a sexual partner in a high-risk group. This was an epidemiologic study, with some follow-up, of all AIDS cases reported to the CDC by early 1983. Surveillance was predominantly passive, supplemented by active follow-up of requests to the CDC for pentamidine (commonly used in the treatment of Pneumocystis carinii pneumonia). A total of 1,299 reported cases meeting CDC definition criteria for AIDS were included in this study. 1) Geographic Trends: U.S. (IB1) 1B1-Sel-11 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Evatt, Bruce L.; Francis, Donald P.; McLane, Mary F.; Lee, Tun H.; Cabradilla, Cirilo; Stein, Sidney F.; Lawrence, Dale N.; McDougal, J. Steven; Spira, Thomas J.; Mullens, James I.; Essex, Myron. Antibodies to Human T Cell Leukaemia Virus-Associated Membrane Antigens in Hemophiliacs: Evidence for Infection Before 1980. The Lancet, 24 September 1983, Vol. 2, No. 8352: 698-701. Centers for Disease Control, Atlanta, Georgia; Emory University, Atlanta, Georgia; Harvard School of Public Health, Boston, Massachusetts. Blood sera collected from Georgia hemophiliacs in 1983 and from New York hemophiliacs between 1976 and 1981 were tested for the presence of antibodies against human T-cell lymphotropic virus (HTLV)-related antigens by means of an indirect living-cell imunofluorescence assay. Five of 45 (11%) Georgia hemophiliacs and 8 of 48 (17%) New York hemophiliacs had antibodies to HTLV-associated cell membrane antigen (HTLV-MA). Seropositivity was evident in the New York samples as early as July 1978. None of the control patients, consisting of patients on chronic hemodialysis or with chronic hepatitis, had a positive serum test. The five hemophiliacs from Georgia with HTLV-MA antibodies had significantly fewer helper T cells than similar HTLV-MA antibody- negative patients. No other significant immunological differences between these groups were found. Antibodies to HTLV-MA were measured by means of indirect living-cell immunofluorescence tests of HTLV-infected cells. Samples causing fluorescence in >50% (or >40%) of the cells were judged to be antibody positive (or weakly positive). Serum specimens were tested for antigens of or antibody to cytomegalovirus, herpes simplex virus types | and 2, Epstein-Barr virus, and hepatitis B virus (HBV), and antibody to hepatitis B virus surface and core antigens and hepatitis A virus. Forty-five hemophiliacs, aged 18 to 60 years, enrolled in the Hemophilia of Georgia home care treatment program volunteered to participate. Control groups consisted of 21 patients on chronic hemodialysis who received transfusion of blood collected in the metropolitan Atlanta area and 29 unselected patients with chronic hepatitis. Frozen serum samples collected between 1976 and 1981 were obtained from 47 hemophiliacs living in New York City. 1) Geographic Trends: U.S. (IBl), 2) Populations: Hemophiliacs (IA3) 1B1-Eva-12 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jaffe, Harold W.; Bregman, Dennis J.; Selik, Richard M. Acquired Immune Deficiency Syndrome in the United States: The First 1,000 Cases. The Journal of Infectious Diseases, August 1983, Vol. 148, No. 2: 339- 345, AIDS Activity, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. The epidemiologic features of the first 1,000 cases of AIDS among persons living in the U.S. and reported to the Centers for Disease Control (CDC) between June 1981 and February 1983 are described. The 1,000 patients, 73% of whom were diagnosed after 1 January 1982, included 284 with Kaposi's sarcoma (KS), 497 with Pneumocystis carinii pneumonia (PCP), 83 with KS and PCP, and 136 with opportunistic infections other than PCP. The overall mortality as of February 1983 was 39.2%. Reports of cases have been received from 32 states and the District of Columbia; New York, California, New Jersey, and Florida accounted for 82.7% of the reports. All but 61 of the patients could be classified into one or more of the following risk groups: homosexual or bisexual men (727), intravenous drug abusers (155), Haitians (50), and patients with hemophilia (7). Surveillance data on cases of AIDS reported to the CDC provide the basis for this descriptive epidemiological study. Surveillance was predominantly passive in nature, through receipt of reports from individual physicians and local and state health departments. The first 1,000 U.S. cases of AIDS reported to the CDC were included for this study. 1) Geographic Trends: U.S. (IB1) 1Bl1-Jaf-13 I. Prevalence and Spread of AIDS/HTLV-III/LAV B. Geographic and Regional Trends 2. Caribbean/South America Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Rodriguez, Luis; Sinangil, Faruk; Godoy, Gerardo; Dewhurst, Steven; Merino, Fernando; Volsky, David J. Antibodies to HTLV-III/LAV Among Aboriginal Amazonian Indians in Venezuela. The Lancet, 16 November 1985, Vol. 2, No. 8464: 1098-1100. Molecular Biology Laboratory, Department of Pathology and Micro- biology, University of Nebraska Medical Center, Omaha, Nebraska; Department Medicina Experimental, Instituto Venezolano de Investi- gaciones Cientificas, Caracas, Venezuela; Department de Parasitologia y Microbiologia, Universidad de Oriente, Cuidad Bolivar, Edo Bolivar, Venezuela. Serum samples from 224 aboriginal Amazon Indians were tested for antibodies to human T-cell lymphotropic virus type [II (HTLV-II[). Nine individuals (4%), five of them female, were positive for antibodies to HTLV-II. Three of these positive samples were collected in 1968. HTLV-II infection rates varied among the ethnic groups and ranged from 13.3% in the Pemon Indians to 3.3% in the Yanoama tribe. All individ- uals tested were apparently healthy at the time of the study. None of the 211 randomly chosen healthy blood donors from Venezuelan cities had antibodies to HTLV-II. The prevalence of HTLV-II antibodies in the Amazon Indians suggests that HTLV-III or a closely related virus may have been endemic in this area for quite some time. This was a case-control seroepidemiologic study of Amazon Indians, using blood samples collected in 1968-69 and 1984-85 for other research purposes. Samples were tested for antibodies to HTLV-III/LAV by an indirect immunofluorescence assay, with positive findings confirmed by Western blot and radioimmunoprecipitation. A total of 224 aboriginal Amazon Indians from various tribes were studied, along with a control group of 211 randomly chosen healthy blood donors from Venezuelan cities. 1) Geographic Trends: South America (Venezuela) (IB2) 1B2-Rod-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Climent, Consuelo, MD; Lasala, German, MD; Velez, Roman, MD; Baldizon, Cesar, MD; Santaella, Maria L., MD. Acquired Immuno Deficiency Syndrome (AIDS): Experience in the Puerto Rico Medical Center. Boletin-Asociacion Medica de Puerto Rico, February 1985, Vol. 77, No. 2: 50-55. Department of Pathology, School of Medicine, University of Puerto Rico (Climent, Lasala, Velez); Laboratory Service Veterans Administration Hospital (Baldizon); Department of Medicine, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico (Santaella). Twenty Puerto Rican cases of AIDS were reviewed, including clinical, immunological, and pathological data. Eleven autopsies were performed. The most common diagnoses were Pneumocystis carinii pneumonia (15 patients) and disseminated Mycobacterium avium- intracellulare (5 patients). Cytomegalovirus was identified in two patients, and Kaposi's sarcoma appeared in five patients. Previously described risk factors were corroborated, i.e., a history of homosexuality, drug addiction, and blood transfusion. The majority of cases had traveled in the U.S., particularly New York, California, and Florida, at some time before or during the onset of their disease. The average duration of illness until death was 4 months. The immunologic profile was consistent with other AIDS patient series, including findings of lower helper/suppressor T-cell ratios. The patients had widespread disease involving most frequently the lungs, spleen and lymph nodes, bone marrow, brain, adrenal glands, liver, and gastrointestinal tract. In most cases the diagnosis was made at postmortem examination. Cytomegalo- virus was not as common in this series of patients as in others. The risk factors, immunological deficiency, and pathological findings for these 20 patients in Puerto Rico were similar to those in the U.S. Medical records of 20 patients with AIDS and autopsy results for 11 of these patients were reviewed. Routine laboratory tests and virologic studies were performed with the assistance of the Centers for Disease Control. Twenty Puerto Rican patients (18 male, 2 female), with ages ranging from 27 to 54 years (mean, 33) were studied. Thirteen were known homosexuals, nine were drug addicts, and one was both. One patient had a history of previous blood transfusion for elective surgery. All patients were residents of Puerto Rico, although seven had traveled to the U.S. 1) Geographical Trends: Caribbean (Puerto Rico) (IB2), 2) Disease Progression: Longevity (IIIC), 3) Diagnostic Definitions and Clinical Manifestations of AIDS (IlIA1,2)) 1B2-Cli-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Pape, Jean W., MD; Liautaud, Bernard, MD; Thomas, Franck, MD; Mathurin, Jean-Robert, MD; St. Amand, Marie-Myrtha A., MD; Boncy, Madeleine; Pean, Vergniaud, MD; Pamphile, Moliere, MD; Laroche, A. Claude, MD; Johnson, Warren D., Jr., MD. Characteristics of the Acquired Immunodeficiency Syndrome (AIDS) in Haiti. The New England Journal of Medicine, 20 October 1983, Vol. 309, No. lé: 945-950. Haitian Study Group on Kaposi's Sarcoma and Opportunistic Infection, Port-au-Prince, Haiti; Division of International Medicine, Department of Medicine, Cornell University Medical College, New York. This study compares different aspects of AIDS in Haiti with AIDS in the U.S. Sixty-one previously healthy Haitians diagnosed with either Kaposi's sarcoma, opportunistic infections (Os), or both were studied between 1979 and 1982. Of those with Ols, 31 met strict Centers for Disease Control criteria for AIDS, while 15 had probable AIDS. The types of Ols and the clinical course of these patients were similar in most respects to those of AIDS patients in the U.S., although tuberculosis, common in Haiti, was present in many patients. The earliest known case of opportunistic infection in Haiti was in July 1978, and the first fulminant case of Kaposi's sarcoma was diagnosed in June 1979. This coincides with the first cases of both conditions in the U.S. The authors believe that AIDS was not present in Haiti prior to 1978. The median age of the 61 patients was 32 years; 85% were male; and the interval between diagnosis and death was 6 months for 80% of these patients. Diarrhea was the most common reason for seeking medical care in patients with OIs. Decreased lymphocyte cell counts and loss of reactivity in the tuberculin skin test were observed in 86% and 100% of patients, respectively. Tuberculosis was present in 33% of the patients with Ols (tuberculosis is common in Haiti, but frequency data were not available). Potential risk factors common in the U.S. (bisexual activity and blood transfusion) were identified in 17% of male and 22% of female patients. Demographic information suggests that patients belonged to all socioeconomic strata of Haitian society. Clinical data were obtained for all study subjects, and demographic characteristics were obtained through a questionnaire or from patient records. A case-control method was used for skin hypersensitivity testing. Sixty-one previously healthy Haitians, who were seen in Port-au-Prince between June 1979 and October 1982 with diagnosed Kaposi's sarcoma (15), OIs (45), or both (1) were studied. 1) Geographic Trends: Caribbean (Haiti) (IB2), 2) Diagnostic Definitions of AIDS: Opportunistic Infections (IIIA2), 3) Disease Progression (I1IC) 1B2-Pap-3 ® In om I. Prevalence and Spread of AIDS/HTLV-III/LAV B. Geographic and Regional Trends 3. Australia Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Sydney AIDS Study Group. The Sydney AIDS Project. The Medical Journal of Australia, 27 October 1984, Vol. 141: 569-573. Commonwealth Institute of Health, The University of Sydney, Sydney, Australia. During a 6-month period in early 1984, 289 male homosexual subjects in Sydney, Australia, were enrolled in a prospective study. The frequency of clinical, epidemiological, and immunological characteristics associated with possible development of AIDS was established in this cohort of men. Almost one-third of the subjects led a "fast-lane" lifestyle, with frequent anonymous sexual contacts; 27% had low helper/suppressor T-cell ratios, and 28% had lymph node disease, features associated with the development of AIDS. Subjects are to be examined every 6 months for at least 2 years to determine the relationship between lifestyle and changes in immunological and antibody status and development of AIDS. This is an ongoing prospective study of urban homosexual men in Australia, employing a self-administered questionnaire of demographic characteristics, recent medical history, drug use, sexual practices, and travel; physical exams; and blood sample collection for full blood counts and T-cell subset analysis. Criteria for participation were homosexual or bisexual orientation and permanent residency in Sydney, Australia. Subjects were self-selected. This report describes the first 289 subjects for whom complete data are available, of 500 subjects enrolled between March and September of 1984. 1) Geographic Trends: Australia (IB3), 2) Populations: Homosexuals (IA1) 1B3-Syd-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Frazer, lan H.; Sarngadharan, M.G.; Mackay, lan R.; Gallo, Robert C. Antibody to Human T Cell Leukaemia Virus Type III in Australian Homosexual Men with Lymphadenopathy. The Medical Journal of Australia, | September 1984, Vol. 141: 274-276. Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, and Royal Melbourne Hospital, Victoria, Australia (Frazer, Mackay); Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Sarngadharan, Gallo). Blood sera from Australian homosexual men and heterosexual controls were tested for antibodies to human T-cell lymphotropic virus type I (HTLV-I) and HTLV-III. In contrast to healthy controls, high levels of antibody to HTLV-III were present in the serum of all six subjects with idiopathic (of unknown cause) lymphadenopathy syndrome (ILS), a disease related to AIDS; these subjects also showed impaired immune function. The sole patient with AIDS had profoundly impaired immune function and no antibody to HTLV-III, while his healthy sexual partner had a low antibody level and normal immune function. Of the five subjects selected for study because of impaired immune function, only one had a questionably low level of antibody to HTLV-II. No heterosexual control subjects had antibody to HTLV-II. Antibody to HTLV-I, earlier believed to be related to AIDS, was lacking in all subjects. The authors of this early study suggest that, in the Australian setting, infection with HTLV-III is the cause of ILS and, by inference, may be the cause of AIDS. Blood sera collected from study participants was tested for antibody to HTLV-I and HTLV-II, the latter by enzyme-linked immunosorbent assay, and immune function was assessed to provide a basis for case-control comparison. Recall of delayed-type hypersensitivity to antigens was testd, and T-cell subsets were counted with Leu2, Leu3, and Leu4 monoclonal antibodies. Subjects included Australian homosexual males derived from 101 participant volunteers in a longitudinal study of immune function and from 17 referred patients, including the following selected for study: 6 patients with unexplained generalized chronic lymphadenopathy for 6 months; 5 without lymphadenopathy who had immunodeficiency on laboratory testing on three occasions over | year; one patient with AIDS and Pneumocystis carinii pneumonia who had not traveled internation- ally, and his regular sexual partner, who had recent sexual contacts in the U.S.; and 6 healthy homosexual men who had normal immune function tests. Other subjects included for the study were six women with autoimmune chronic active hepatitis with hyperglobulinemia (an 1B3-Fra-2 abnormally large amount of globulins in the circulating blood plasma) and nine healthy laboratory workers. Policy Keys: 1) Geographic Trends: Australia (IB3), 2) Precursors of AIDS (IIIB), 3) Populations: Homosexuals (IA1) [. Prevalence and Spread of AIDS/HTLV-III/LAV B. Geographic and Regional Trends 4. Europe Author(s): Title: Source: Institution: Findings: Method: Sample Size: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Update: Acquired Immunodeficiency Syndrome--Europe. Morbidity and Mortality Weekly Report, 24 January 1986, Vol. 35, No. 3: 35-46. Centers for Disease Control, Atlanta, Georgia. As of September 1985, 1,573 cases of AIDS had been reported to the World Health Organization (WHO) European Collaborating Centre on AIDS by the 21 countries participating. The new cases represent an average increase of 27 cases per week. Of the 1,573 patients, 792 have died to date. The greatest increases in incidence were in the Federal Republic of Germany (5 to 6 per week), France (5 to 6 per week), the United Kingdom (3 to 4 per week), and Italy (3 per week). Five countries (Czechoslovakia, Hungary, Iceland, Poland, and the U.S.S.R.) have reported no cases. The incidence of AIDS was calculated from 1985 population estimates. The highest rates (per million population) were noted in Switzerland (11.8), Denmark (11.2), and France (8.5), compared with the U.S. incidence rate of 60.0 cases per million population. A total of 1,025 European patients (65%) presented with one or more opportunistic infections. The highest case fatality rate was for those with opportunistic infections and Kaposi's sarcoma (KS) (59%), while the rate for opportunistic infections alone was 56%, and for KS alone 25%. Males accounted for 92% of cases, and 42% of cases were in the 30 to 39 age group. Thirty-six pediatric cases were identified; 24 (67%) either had parents with AIDS or parents in a group at high risk for AIDS. Distributions by geographic region are presented, as are distributions by risk group. In addition, a review of public health measures related to blood donation is presented. This information was gathered by questionnaires distributed to the 21 participating European countries. Systematic screening of donations became effective in 16 of the 21 countries between June and November 1985. In 13 countries the screening 1s mandatory. The test used is the enzyme-linked immunosorbent assay (ELISA), and follow-up is done with a second ELISA or a Western blot test. Measures to exclude donors at risk have been taken in all countries except Czechoslovakia, Finland, and Poland. This report reviews the epidemiology of AIDS in Europe, presenting incidence rates, case fatality rates, geographic distributions, and distributions by risk group. Findings are based on surveillance data reported by 21 participating countries to the WHO European Collaborating Centre on AIDS. This report describes 1,573 European cases of AIDS in 21 countries. 1B4-Cen-1 Policy Keys: 1) Geographic Trends: Europe (IB4), 2) Disease Stages: Clinical Manifestation and Fatality (IIIC), 3) Blood Product Safety: Seroprevalence (VB2) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Sirianni, M.C.; Rossi, P.; Moroni, M.; Romagnani, S.; Lazzarin, A.; Carbonari, M.; Scarpati, B.; Mariani, M.; Manconi, P.E.; Del Giacco, G.S.; Aiuti, F. Demonstration of Antibodies to Human T-Lymphotropic Retrovirus Type III in Lymphadenopathy Syndrome Patients and in Individuals at Risk for Acquired Immune Deficiency Syndrome (AIDS) in Italy. American Journal of Epidemiology, 1986, Vol. 123, No. 2: 308-315. Department of Clinical Immunology, Institute of Internal Medicine III and Department of Haematology, University "La Sapienza," Rome; Institute of Internal Medicine, University of Cagliari; Department of Infectious Diseases, University of Milan; Department of Clinical Immunology, University of Florence, Italy. This epidemiological survey investigated the distribution of lymphadenopathy syndrome (LAS) in six Italian cities and its correlation with human T-cell lymphotropic virus type III (HTLV-III) in individuals at risk for AIDS in Italy. Antibodies to HTLV-II were demonstrated in the sera of 7 of 9 (78%) patients with AIDS and in 115 of 180 (64%) LAS patients. The highest percentage of positive sera was found in hemophiliacs (6 of 6), in homosexuals (12 of 15), and in drug addicts from Rome (26 of 30). For persons at risk for AIDS or lymphadenopathy, the percentage of positive sera ranged from zero in polytransfused subjects to 8.5% in homosexuals, 14% in drug addicts, and 19.5% in hemophiliacs. No positive sera were found among 660 healthy individuals, including relatives of patients with AIDS or LAS, or in 342 patients with immunologic or infectious diseases. Study findings show that, despite the small number of cases of AIDS observed in Italy since 1981, a high proportion of patients with LAS are positive for HTLV-III antibodies and that these antibodies are also present in the majority of AIDS cases in Italy and in a certain percentage of individuals at high risk for AIDS. These results strongly suggest that HTLV-II is the causative agent of AIDS and LAS. The data also suggest that, since none of the healthy subjects were positive while a substantial percentage of people at risk for AIDS showed antibody to HTLV-III, HTLV-III infection is related to exposure, whereas disease, especially AIDS, may occur primarily in compromised hosts. Serum samples were collected and tested for antibody to HTLV-III by immunofluorescence assay, and standard methods for testing skin sensitivity to antigens were used. Serum samples were obtained from individuals in six Italian cities: Rome, Milan, Florence, Naples, Cagliari, and Verona. The study population consisted of 538 cases, including 9 patients with AIDS, 180 patients with LAS (159 drug addicts, 15 homosexuals, and 6 hemophiliacs), and 349 individuals at risk for AIDS or LAS, including 70 high-promiscuity homosexuals or bisexuals, 166 intravenous drug addicts, 113 hemophiliacs, and 18 polytransfused patients. For comparison, 1B4-Sir-2 Policy Keys: control sera were collected from 660 healthy individuals, 168 patients with several viral diseases (including hepatitis, infectious mononucleosis, cytomegalovirus, herpes simplex, etc.), and 174 patients with immune or lymphoproliferative disorders and classic Kaposi's sarcoma. 1) Geographic Trends: Europe (Italy) (IB4), 2) Populations: Hemophiliacs, Homosexuals, Drug Abusers (IA3,1,2), 3) Disease Stages (IIIC), 4) Cofactors: Immunocompromised Host (IC3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Alutl, Fs; Rossi, Pg Sirlannl, M.C.; Carbonari, M.; Popovic, M.; Sarngadharan, M.G.; Contu, L.; Moroni, M.; Romagnani, S.; Gallo, R.C. [gM and IgG Antibodies to Human T Cell Lymphotropic Retrovirus (HTLV-II in Lymphadenopathy Syndrome and Subjects at Risk for AIDS in Italy. British Medical Journal, 20 July 1985, Vol. 291, No. 6489: 165-166. Department of Clinical Immunology, Institute of Internal Medicine III, University "La Sapienza," Rome; Institute of Internal Medicine, University of Cagliari; Department of Infectious Diseases, University of Milan; Department of Clinical Immunology, University of Florence, Italy; Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland. This study assessed the prevalence of specific antibodies to human T-cell lymphotropic virus type [I (HTLV-II) in Italian patients with lymphadenopathy syndrome or AIDS and those at risk for AIDS. Of 320 patients with lymphadenopathy syndrome, 235 had antibodies to HTLV- III, the proportions being highest in hemophiliacs, homosexuals, and drug addicts. Eleven of 12 AIDS patients had antibodies to HTLV-III, and 78 of 439 patients at risk for AIDS had antibodies to the virus. No control subjects were positive for HTLV-III antibodies. For this study, blood serum samples were obtained from patients and healthy subjects in Rome, Milan, Florence, Naples, Cagliari, Verona, Turin, Genoa, Viterbo, and Catanzaro. Sera were tested for antibodies to HTLV-II, measured by immunofluorescence assay and, in a few patients, by Western blotting. In 82 patients positive for HTLV-II antibodies, immunoglobulin M antibody values were measured by fluorescence testing. Study subjects included 320 patients with lymphadenopathy syndrome, of whom 298 were drug addicts, 16 were homosexuals, and six were hemophiliacs; 12 patients with AIDS; and 439 patients at risk for AIDS, including 70 homosexuals or bisexuals who had more than 50 partners per year, 259 intravenous heroin abusers, 88 hemophiliacs, and 22 other patients with a history of multiple transfusions. A total of 660 healthy controls were selected, including 530 adult males, 80 adult females, and 50 children. Adults were aged 18 to 65 years. Healthy subjects included 280 selected from five different blood banks, 45 laboratory and hospital personnel, 140 military service men, and 30 relatives of patients with AIDS and lymphadenopathy syndrome. The study also tested sera from 117 patients with infectious and miscellaneous diseases (viral diseases, lymphoproliferative disorders, and classic Kaposi's sarcoma). 1) Geographic Trends: Europe (Italy) (IB4), 2) Precursors of AIDS: Lymphadenopathy (IIIB) IB4-Aiu-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Mortimer, P.P.; Jesson, W.J.; Vandervelde, E.M.; Pereira, M.S. Prevalence of Antibody to Human T Lymphotropic Virus Type III by Risk Group and Area, United Kingdom 1978-84. British Medical Journal, 20 April 1985, Vol. 290: 1176-1178. Virus Reference Laboratory, Central Public Health Laboratory, London, England. : Three high-risk groups, including homosexuals, hemophiliacs, and intravenous drug abusers, were tested for the presence of antibody to human T-cell lymphotropic virus type III (HTLV-II) with a radioimmunoassay and an immunofluorescence test. Results by both methods corresponded closely. HTLV-III antibody was already present in some British homosexuals in 1980 and in some British hemophiliacs in 1981. Prevalence of HTLV-II antibody since then has increased in London homosexual patients from 5% in 1980 to 34% in 1984. In 1984, 43 of 126 (34%) homosexuals attending clinics in London for sexually transmitted diseases had HTLV-II antibodies, while at centers outside London 49 of 955 (5%) had HTLV-III antibodies. Of hemophiliacs sampled the same year, 31 of 81 (38%) had HTLV-II antibodies. Most of these patients (21 of 31) were regular recipients of commercial factor VIII concentrates. Only 5 of 203 (2.5%) intravenous drug abusers had HTLV- [II antibodies in 1984. These findings confirm those of a previous seroepidemiological survey of HTLV-II infection in Britain and also show that infection has become increasingly widespread since 1980-81 in the two groups mainly affected, suggesting that HTLV-II has become prevalent in homosexuals throughout the country. Two tests were used to detect antibodies to HTLV-II, a radioimmuno- assay and an immunofluorescence test. A total of 2,150 patients in three groups at risk were tested for antibody to HTLV-II. Blood serum samples were collected from male homosex- uals attending clinics for sexually transmitted diseases: 704 in London between 1980 and 1984, and 955 outside London mostly in 1984. Blood sera collected from hemophiliacs were from several treatment centers from 1978 on. A total of 525 samples from 288 patients were analyzed. Also, 203 intravenous drug abusers from all over England were examined. 1) Geographic Trends: Europe (England) (IB4), 2) Populations: Homosexuals, Hemophiliacs, [.V. Drug Abusers (IA1,3,2) 1B4-Mor-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Gerstoft, J.; Nielsen, J.O.; Dickmeiss, E.; Ronne, T.; Platz, P.; Mathiesen, L. The Acquired Immunodeficiency Syndrome (AIDS) in Denmark. Acta Medica Scandinavica, 1985, Vol. 217: 213-224. Department of Infectious Diseases M and Tissue Typing Laboratory of the Department of Clinical Immunology, Rigshospitalet; Department of Internal Medicine, Division of Rheumatology, and Department of Clinical Immunology, Hvidovre Hospital; and Statens Seruminstitut, Department of Rubella and Department of Epidemiology, Copenhagen, Denmark. Twenty Danish patients with AIDS had been diagnosed by January 1984, 14 of them after 1982. Of the total, 18 patients were male homosexuals, 8 of whom had visited the U.S. after 1979. Two patients were hetero- sexual males with a history of sexual contacts in central Africa, suggesting possible heterosexual transmission from women to men. AIDS had not been observed in drug abusers, hemophiliacs, or transfused persons not otherwise at risk in Denmark at the time of this study. The patients’ clinical picture varied according to the presence of Kaposi's sarcoma or other opportunistic infections, but was in general similar to that reported in the U.S. Survival 2 years after diagnosis was 16%. T-cell studies revealed that the AIDS patients' immune status differed from that of controls and of healthy homosexual men in either a very low number of helper cells or lower helper/suppressor T-cell ratios. Functional immunological studies revealed decreased natural killer cell activity as well. This was an epidemiologic investigation of all Danish AIDS patients, their immunological status, and known risk factors, as well as case-control studies of immunodeficiency. All 20 Danish AIDS patients diagnosed through January 1984 were studied. The controls for immunological testing were 66 healthy promiscuous homosexual men and 31 other male controls. 1) Geographical Trends: Europe (Denmark) (IB#4), 2) Cofactors: Contact With U.S. Homosexuals or Central Africans (IC4), 3) Transmission: Sexual Activity (IIA), 4) Disease Stages: Longevity (IIIC), 5) Immunological Aspects (IIE) 1B4-Ger-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Hehlmann, R.; Kreeb, G.; Erfle, V.; Piechowiak, H.; Kruger, G.; and Goebel, F.D. IgG-Antibodies to HTLV-III in Patients with AIDS, LAS, and Persons at Risk of AIDS in West Germany. Blut, 1985, Vol. 50: 13-18. Medizinische Poliklinik der Universitat, Munich (Hehlmann, Kreeb, Piechowiak, Goebel); Abteilung fur Pathologie der GSF, Neuherberg (Erfle); Pathologisches Institut der Universitat, Koln, Federal Republic of Germany (Kruger). In this seroepidemiological study of the prevalence of human T-cell lymphotropic virus type III (HTLV-II) in West Germany, serum samples from 26 patients with AIDS, 33 patients with lymphadenopathy syndrome (LAS) or AIDS-related complex (ARC), and 113 homosexual men at risk for AIDS were screened for antibodies to HTLV-II. Twenty-two of 26 (84.6%) AIDS patients, 24 of 33 (72.7%) LAS patients, and 44 of 113 (38.9%) healthy homosexual men with increased risk of AIDS were found to be positive for antibodies to HTLV-II. Heterosexual controls, including 23 healthy laboratory workers and 5 medical personnel who had contact with AIDS patients, did not show antibodies to HTLV-II. This was a case-control study of AIDS and AIDS-related patients, homosexuals at risk for AIDS, and healthy controls, testing blood samples for HTLV-III antibodies. Twenty-six patients with AIDS, 33 patients with LAS or ARC, and 113 homosexual men at risk for AIDS were studied. Heterosexual controls included 23 healthy laboratory workers and 5 medical personnel who had contact with AIDS patients. 1) Geographic Trends: Europe (West Germany) (IB4), 1B4-Heh-6 Author(s): Title: Source: Institution: Findings: Method: Hunsmann, G.; Schneider, J.; Bayer, H.; Kurth, R.; Werner, A.; Brede, H.D.; Erfle, V.; Mellert, W.; Brodt, H.R.; Bergmann, L.; Helm, lL; Scharrer, [.; Kreuz, W.; Berthold, H.; Wernet, P.; Schneider, E.M.; Schimpf, K.; Egli, U.; Bienzle, U.; Schmitz, H.; Kern, P.; Kruger, G.; Rasokat, H.; Lechler, E.; Seifried, E.; Hellstern, P.; Schneider, W.; Holzer, E.; Goebel, F.-D.; Hehlmann, R. Seroepidemiology of HTLV-II (LAV) in the Federal Republic of Germany. Klinische Wochen-Schrift, 1985, Vol. 63: 233-235. Deutsches Primatenzentrum, Gottingen (Hunsmann, Schneider, Bayer); Paul-Ehrlich Institut, Frankfurt (Kurth, Werner, Brede); Gesellschaft fur Strahlen und Umweltforschung, Neuherberg (Erfle, Mellert); Zentrum Innere Medizin, Universitat Frankfurt (Brodt, Bergmann, Helm, Scharrer, Kreuz); Zentrum fur Hygiene, Universitat Freiburg (Berthold); Medizinische Klinik, Universitat Tubingen (Wernet, Schneider); Rehabili- tations Klinik, Heidelberg (Schimpf); Institut fur Experimentelle Hamotologie und Transfusions-Medizin, Universitat Bonn (Egli); Landesinstitut fur Tropenmedizin, Berlin (Bienzle); Bernhard-Nocht- Institut, Hamburg (Schmitz, Kern); Pathologisches Institut, Universitat Koln (Kruger); Dermatologische Klinik, Universitat Koln (Rasokat); 1. Medizinische Klinik, Universitat Koln (Lechler); Zentrum Innere Medizin, Universitat Ulm (Seifried); Abteilung fur klinische Hamostaseologie, Universitat Homburg/Saar (Hellstern); Abteilung fur Transfusionswesen, Universitat Tubingen (Schneider); 4. Medizinische Abteilung, Krankenhaus Munchen-Schwabing (Holzer); and Medizinische Poliklinik, Universitat Munchen (Goebel, Hehlmann). This study reports results of a survey on the prevalence of antibody to human T-cell lymphotropic virus type II (HTLV-II) in the Federal Republic of Germany based on sera examined in three laboratories in 1984. Of the AIDS patients tested, 81% had antibodies to HTLV-II; of the 1,967 in the male homosexual group, 39% were positive for HTLV-II antibody (25% of the asymptomatic homosexual subgroup and 72% of those with lymphadenopathy or AIDS-related complex); 42% of hemophil- iacs tested positive, as did 34% of intravenous (I.V.) drug abusers. No positive tests were found among the potential risk groups (prostitutes, laboratory personnel, polytransfused patients, and hepatitus B virus (HBV)-vaccinated persons); 0.17% of randomly selected blood donors were positive for HTLV-III antibody. Antibody to HTLV-III was not found in hemophiliacs treated only with heat-inactivated blood-clotting factor VIII, whereas antibody was present in up to 80% of other hemophiliacs. Rates of infection for risk groups are similar to those for other European countries but lower than in the U.S. In this multicenter seroepidemiological survey, blood specimens were collected from clinics, treatment centers, and blood banks all over the Federal Republic of Germany. All were blindly tested for antibodies to HTLV-III by enzyme-linked immunosorbent assay with positive or questionable reactions confirmed by immunoblotting with purified HTLV- [Il or one of two other methods. Positive findings were reported for each subject group and for all male homosexuals as a single group. 1B4-Hun-7 Sample Size: Policy Keys: A total of 10,281 West Germans were tested in this study in 1984: 53 AIDS patients; 3,911 members of risk groups (814 asymptomatic male homosexuals, 385 male homosexuals with lymphadenopathy or AIDS- related complex (ARC), 768 other male homosexuals, 710 hemophiliacs, and 35 L[.V. drug abusers); 276 members of potential risk groups (101 prostitutes, 42 laboratory personnel, 35 polytransfused patients, 98 HBV vaccinated persons); and 7,240 randomly selected blood donors. Subject groups were drawn from various locales in the Federal Republic of Germany, many from diverse urban areas. 1) Geographic Trends: Europe (Federal Republic of Germany) (IB4), 2) Blood Product Safety: Viral Inactivation (VB3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Brunet, J.B. Acquired Immune Deficiency Syndrome in France. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. I: 66. Sous-Direction de la Prevention Generale et de I'Environment, Ministere des Affaires Sociales et de la Solidarite Nationale, Paris, France. This article reports early AIDS cases in France. Ninety-four AIDS patients had been reported in France by October 1983. Fifty-five were male homosexuals, | was a hemophiliac, 10 were Haitian, 18 were African, and 10 were heterosexual men. The probable source of infection was sexual contact with U.S. homosexuals for 26 patients and European homosexuals for 28 patients, Haiti for 14 patients, central Africa for 22 patients, and use of blood products for | patient. The infection source for three other heterosexual patients was unknown. Kaposi's sarcoma was present in 25 patients, opportunistic infections in 57 patients, and both conditions in 12 patients. This was an epidemiologic study of all AIDS patients reported in France by October 1983. Only tables are presented, no text. The data include 94 AIDS patients reported in France by October 1983. 1) Geographic Trends: Europe (France) (IB4), 2) Cofactors: Contact with U.S. Homosexuals, Visits to Haiti or Central Africa (IC4) 1B4-Bru-8 Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Clauvel, J.P.; Couderc, J.L.; Tricot, G.; Rabian, C.; D'Agay, M.F.; Brouet, J.C. Persistent Lymphadenopathy in Patients at Risk of Contracting Acquired Immune Deficiency Syndrome. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. I: 72. Department of Immunohematology (Clauvel, Couderc, Brouet), Division of Pathology (Tricot, D'Agay), and Laboratory of Immunology (Rabian), Hopital Saint-Louis, Paris, France. Twenty-five French patients at risk for AIDS who had chronic, multisite lymphadenopathy but no opportunistic infections or malignancies were studied. The patients were 23 homosexuals, one hemophiliac, and one Haitian. Two of the homosexual men also used intravenous (I.V.) drugs. Ten patients had been living in the U.S. or Haiti. Lymphadenopathy was generalized in 4 cases and confined to the neck and armpits in the remaining 21 cases. Four patients had weight loss, and one had oral fungal infection (Candida). Six of the homosexual men had recurrent herpes simplex infection. Blood tests showed an inversion of the normal helper/suppressor T-cell ratio in 17 cases and lowered helper T-cell counts in 10 cases. Antibodies to Toxoplasma gondii were found in 10 of 15 cases; antibodies to cytomegalovirus were found in 3 of 17 cases; and antibodies to Epstein-Barr virus were found in 6 of 11 cases. During the 3 to 24 months of follow-up, the lymph node condition was always present. Twenty-four patients were clinically well at publication, and one had developed cytomegalovirus-associated pneumonia. This prospective study was conducted for 3 to 24 months of persons at risk for AIDS, with lymph node swelling present for at least 6 months at two or more sites not in the groin. Clinical histories and blood tests for immunologic status were conducted. Twenty-five residents of France are included in this study: 23 homosexuals, one hemophiliac, and one Haitian. Two of the homosexual men also used [.V. drugs. Ten patients had been living in the U.S. or Haiti. All patients were at risk for AIDS and had chronic swollen lymph nodes. 1) Geographic Trends: Europe (France) (IB4), 2) Precursors of AIDS (IIIB) 1B4-Cla-9 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Clumeck, N. Acquired Immune Deficiency Syndrome in Belgium. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. 1: 59-60. Division of Infectious Diseases, St. Pierre Hospital, Brussels, Belgium. This article reports early cases of AIDS in Belgium. By August 1983, 38 cases of AIDS had been reported in Belgium; 89% of these cases were blacks who originated from central Africa and denied homosexuality, bisexuality, or drug abuse. Two of the remaining patients were male homosexuals, and one patient was a white woman with no known AIDS risk factors who had lived in Belgium with a native of Zaire. Among the African patients, the male-to-female ratio was 1:5; there were 32 adults (mean age, 35 years) and 2 infants. The country of origin of 31 patients was Zaire; the others came from Rwanda, Burundi, or Chad. All patients had severe opportunistic infections, the most common being candidiasis. Cryptococcosis, Toxoplasma gondii, brain abscesses, and Pneumocystis carinii pneumonia were the leading causes of death. The overall death rate was 45% by the time of this report. Kaposi's sarcoma was noted in only four cases. In all patients there was a marked decrease in the helper/suppressor T-cell ratios. This series of patients is noteworthy because of the high prevalence of non-European (African) cases. Although the mode of transmission in this population is unknown, a possibility may be heterosexual transmission. Poor hygiene during medical procedures is also suggested as a possible mode of transmission. This is an epidemiologic summary of all confirmed AIDS cases in Belgium; data are displayed by year of diagnosis, probable source of infection, and type of infection or malignancy for the homosexual and African groups. All 38 confirmed AIDS patients in Belgium up until August 1983 were studied. 1) Geographic Trends: Europe (Belgium) (IB4), 2) Geographic Trends: Africa (IB5), 3) Transmission: Sexual Activity (IIA), 4) Transmission: Medical Practices in Africa (IIG) 1B4-C1lu-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Glauser, M.P.; Francioli, P. Clinical and Epidemiological Survey of Acquired Immune Deficiency Syndrome in Europe. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. 1: 55-33. Division des Maladies Infectieuses, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. A survey was conducted of health departments in Europe. On the basis of the number of patients reported annually, it would appear that AIDS has reached epidemic proportions in Europe. More than half of the 243 cases documented in the survey were reported during the first 9 months of 1983. . The most important risk factor for AIDS among Europian males is homo- sexuality (58% of cases). Black persons from central Africa (26%) and Caucasians who have had intimate contact with natives from central Africa (3%) are new risk groups defined in Europe. These patients had no known history of homosexuality or drug abuse. The clinical presentation of the disease in the two most important groups, homosexual males and persons from central Africa, differed slightly. Kaposi's sarcoma was more frequent in the former group (40%) than in the latter. Pneumocystis carinii pneumonia was the most frequent opportunistic infection in homosexuals, while fungal infections predominated in African patients. The authors conclude that AIDS has become established in Europe mainly through homosexual contacts and cases imported from central Africa. Epidemiologic survey data were obtained by a questionnaire sent to physicians and health authorities of several European countries which had reported 94% of all European AIDS cases up to 15 October 1983. All 243 AIDS cases diagnosed in Europe by late 1983 are described. 1) Geographic Trends: Europe (IB4), 2) Diagnostic Definitions of AIDS: Kaposi's Sacroma, Opportunistic Infections (IIIAl,2), 3) Populations: Homosexuals, Minorities (Africans), Heterosexuals (IAl,5,6), 4) Cofactors: Risk Group and Clinical Manifestations (IC4) 1B4-Gla-11 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: L'age-Stehr, J. Acquired Immune Deficiency Syndrome in the Federal Republic of Germany. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. 1: 61. Robert Koch-Institut des Bundesgesundheitsamtes, Berlin, Federal Republic of Germany. By September 1983, 41 AIDS cases had been reported in the Federal Republic of Germany (FRG). Forty patients were male, and of these, 36 were likely homosexuals. One patient was hemophiliac. No AIDS patients had intravenous drug abuse as the sole risk factor. All patients diagnosed before April 1982 had a history of travel to the U.S., Haiti, or central Africa during the past 5 years. Among recently diagnosed patients, the number without such history of travel is increasing. Sixteen of the 36 homosexual patients developed Kaposi's sarcoma. Five of these also had severe opportunistic infections. Only one patient in the group with no known risk factors developed Kaposi's sarcoma. The spectrum of opportunistic infections seen in U.S. AIDS cases was also seen in the FRG. In October 1983, three more patients were reported. Of the total 44 patients, 14 had died by the time of publication (February 1984). This was an epidemiologic study of all known AIDS patients reported in the FRG before September 1983. Data were volunteered by patients’ physicians, as there was no centralized reporting of AIDS in the FRG at this time. Forty-one AIDS cases reported in the FRG by September 1983 were studied; 40 patients were male, and of these, 36 were likely homosexuals. One patient was hemophiliac. 1) Geographic Trends: Europe (West Germany) (IB4) 1B4-Lag-12 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: McEvoy, M. Acquired Immune Deficiency Syndrome in the United Kingdom. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. 1: 63-64. Communicable Disease Surveillance Centre, Public Health Laboratory Service, London, England. By October 1983, 24 cases of AIDS (23 male, | female) had been confirmed in the U.K. One case was diagnosed prior to 1980, 2 cases in 1981, 10 cases in 1982, and ll cases in 1983. All patients were caucasians. There were 10 cases of Kaposi's sarcoma without Pneumocystis carinii pneumonia, seven cases of P. carinii pneumonia without Kaposi's sarcoma, and six cases of other opportunistic infections. Of the 24 patients, 20 were homosexual and 1 was also a drug abuser. Two heterosexual men were hemophiliac and had received American blood-clotting factor VIII concentrate. Two other heterosexual males had no apparent risk factors. The female patient had multiple sexual partners. Sixteen of the homosexual patients had had sexual contact with U.S. or Caribbean nationals or had visited these countries within the 4 years prior to the development of symptoms. This report describes the epidemiologic characteristics of all U.K. AIDS patients up until late 1983. Twenty-four AIDS cases (as defined by the U.S. Centers for Disease Control) identified in the U.K. through October 1983 are described. 1) Geographic Trends: Europe (United Kingdom) (IB4), 2) Transmission: Sexual Activity (IIA), 3) Cofactors: Contact with U.S. or Caribbean Homosexuals (IC4) 1B4-McE-13 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Repo, H.; Valle, S.-L.; Ranki, A.-M.; Pettersson, T. Acquired Immune Deficiency Syndrome in Scandinavia. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. I: 63. Aurora Hospital, Helsinki, Finland. This article reports early AIDS cases in Scandinavia. Before October 1983, 20 AIDS patients had been diagnosed in Scandinavia (13 in Denmark, 2 in Finland, 2 in Norway, 3 in Sweden). Two AIDS patients had been found by screening volunteers in a gay disco in Helsinki, Finland. In Denmark 6 of the 13 AIDS patients had Kaposi's sarcoma (KS); in Finland one had KS and the other Pneumocystis carinii pneumonia; none of the patients in Norway and Sweden had KS. The finding of two patients with manifest AIDS in Finland within 2 weeks of initiation of screening demonstrates the value of this process. This was an epidemiologic study of known Scandinavian cases reported prior to October 1983. A screening study was also conducted in Finland, where no AIDS cases had been reported prior to June 1983. In a gay disco in Helsinki, the symptoms and risk factors for AIDS were described, and persons with AIDS symptoms were invited to undergo examination and testing. A questionnaire was also completed relating to lifestyle, risk behaviors, previous infections, etc. Twenty AIDS patients reported in Scandinavia by October 1983 were studied, two of whom were identified by screening patrons of a gay bar in Helsinki, Finland. 1) Geographic Trends: Europe (Scandinavia) (IB4) 1B4-Rep-14 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Vandenbroucke-Grauls, C.M.; Verhoef, J. Acquired Immune Deficiency Syndrome in the Netherlands. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. 1: 62. Klinische Bacteriologie, Academisch Ziekenhuis, Utrecht, The Netherlands. This article reports early AIDS cases in the Netherlands. By September 1983, eight cases of AIDS had been reported in the Netherlands. Seven of these cases occurred in homosexual men; one patient denied homosexual contact. Six of the homosexual patients were also drug abusers. One patient was of Nicaraguan origin. In four of the cases, individuals had contact with U.S. homosexuals. All homosexual patients had repeated episodes (four to six) of gonorrhea and syphilis. The one patient who denied homosexual contact admitted to occasional contact with a prostitute. Three of the homosexual patients developed Kaposi's sarcoma. The whole spectrum of opportunistic infections seen in other AIDS patients was observed. In October 1983, three more cases were reported. Of these ll total cases, 7 had died by the time of this report (February 1984). This was an epidemiologic study of all AIDS patients confirmed in the Netherlands by late 1983. Patients included were 8 AIDS cases in the Netherlands prior to September /October 1983, plus three additional later cases. 1) Geographic Trends: Europe (Netherlands) (IB4), 2) Cofactors: Contact with U.S. Homosexuals (IC#4), 3) Cofactors: Other Sexually Transmitted Diseases (IC3), 4) Transmission: Sexual Activity (with Prostitute) (IIA) 1B4-Van-15 Author(s): Title: Source: Institution: Findings: Method: The Institute of Cancer Research. The Epidemiology of AIDS in Europe. European Journal of Cancer and Clinical Oncology, 1984, Vol. 20, No. 2: 157-164. The Institute of Cancer Research, Aarhus, Denmark. This survey of health departments and other investigation units in Europe found that 200 cases of AIDS had been diagnosed as of September 1983. Eight cases occurred prior to 1979 and were found by retrospective searches. The number of cases diagnosed annually thereafter increased steadily from 2 cases in 1980 to 104 cases in 1983. Cases were predominantly adult males (87%). All but | of the 21 adult female cases were African (17 of 42 African cases) or Haitian (3 of 8 Haitian cases). Three cases were diagnosed in children. The European cases were analyzed separately from those of patients with non-European origins. Among the [48 European cases, risk groups included homosexual or bisexual men (79.7%), homosexual men using intravenous ([.V.) drugs (1.4%), heterosexual [.V. drug abusers (1.4%), and hemophiliacs (4.1%). Another 13.5% did not fit any of these risk roups. France reported the largest number of cases among Europeans 51) and Germany was second (30), but almost every area of Europe reported at least one case. In the eastern European nations, only one case was diagnosed in a European. Non-European cases included one U.S. citizen and one Nicaraguan, both of whom were homosexual or bisexual men. The remaining 50 non- European cases were from Africa (42) and Haiti (8). All the cases from Belgium (26) were Africans, and additional African cases were diagnosed in France (11), Switzerland (4), and Czechoslovakia (1). All the Haitians were diagnosed in France. Among the European cases, patients with opportunistic infections were most common (73.6%), including those who also had Kaposi's sarcoma (KS) (15.5%). Diseases diagnosed as AIDS without either an opportunistic infection or KS were reported in 3.4% of cases, but this reflected a lack of information in some cases. KS was notably more common amon homosexual and bisexual men. Of 57 European cases with KS, 50 (87.7% occurred among homosexual men. No cases of KS occurred among the six hemophiliac AIDS patients. Among the African cases, 31 (73.8%) had opportunistic infections, including 2 who also had KS. Five (11.9%) had KS as the sole manifes- tation, and the remainder (14.3%) had other manifestations, or infor- mation was inadequate. The Haitian cases all had opportunistic infec- tions, and two also had KS. This epidemiology study describes all AIDS cases diagnosed in Europe by September 1983. Questionnaires were completed by national health departments and other investigation units to obtain data about number of 1B4-Ins-16 Sample Size: Policy Keys: cases (although definitions of AIDS varied somewhat), distribution and place of occurrence, risk group association, and clinical features. Duplications were eliminated, and the most complete data were used for each reported case. All 200 AIDS cases diagnosed in Europe through August 1983 were included. Cases were generally defined by Centers for Disease Control criteria, along with immune system abnormality (decrease in helper/suppressor T-cell ratio), although definitions varied somewhat. 1) Geographic Trends: Europe (IB4), 2) Populations: Homosexuals, I.V. Drug Abusers, Hemophiliacs, Minorities (Africans and Haitians), Heterosexuals (IA1,2,3,5,6), 3) Diagnostic Definitions of AIDS: Kaposi's Sarcoma, Opportunistic Infections (IlIA1,2), 4) Cofactors: Risk Group and Clinical Manifestations (IC4) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Bouvet, E.; Brunet, J.B.; Chaperon, J.; Gluckmann, J.C.; Kernbaum, S.; Klatzmann, D.; Lachiver, L.D.; Leibowitch, J.; Mayaud, C.; Picard, O.; Revuz, J.; Rozenbaum, W.; Villalonga; Weisselberg, C. Sarcome de Kaposi et Infections Opportunistes Chez des Sujets Jeunes sans Antecedent Susceptible d'Entrainer une Immuno-depression. La Presse Medicale, 5 November 1983, Vol. 12, No. 39: 2431-2434, Groupe de travail francais sur le syndrome d'immuno-deficit acquis: Ministere de la Sante (Bouvet, Chaperon, Weisselberg); Institut Leon Mba (Brunet); Hopital Pitie-Salpetriere (Gluckman, Klatzmann, Rozenbaum); Hopital Claude Bernard (Kernbaum); Institut Prophylactique (Lachiver); Hopital Raymond Poincare (Leibowitch); Hopital Tenon (Mayaud); Hopital Tarnier (Picard); Hopital Henri Mondor (Revuz); Association des Medicins Gays (Villalonga), France. To more precisely characterize the AIDS phenomenon in France, a study group collected 25 AIDS cases for examination. All but 2 of the 25 cases were from the Paris area. Diagnoses occurred from 1974 to 1982, with 16 cases diagnosed in the last 2 years (1981 and 1982). The 25 cases included Ll cases of isolated Kaposi's sarcoma (KS), three cases of KS plus opportunistic infection, and 15 cases of single or multiple opportunistic infection. Sixteen subjects were male homosexuals, seven were heterosexual males, four were women, and two were males of unknown sexual preference. Five male homosexuals had traveled to the U.S., and five patients had visited Haiti, of whom three were native Haitians. One French patient had been transfused; four patients had visited equatorial Africa, two of whom were Zairian. The authors state that these study findings show that AIDS is present in France under multiple clinical aspects. French subjects at risk appear to be male homosexuals, especially those with several sexual partners, but they have a lower statistical risk of contracting AIDS in France than in the U.S. None of the French patients were drug addicts or hemophiliacs. In this epidemiological study, conducted by a French multidisciplinary group from March to December 1982, 25 cases of AIDS were defined (in subjects under age 60), as KS and/or severe opportunistic infection due to deficiency of the normal cell-mediated immune defense mechanism against the causative agents. Information on cases was validated by telephone contact with the patient's physician, and a questionnaire was used which included information about risk factors, notably the patient's sex and sexual behavior. Information about use of intravenous drugs or "poppers" (amyl nitrite) and foreign travel from five deceased patients was incomplete, but their data included age, sex, nationality, and foreign travel collected from medical records. Twenty-five French cases of AIDS diagnosed between 1974 and 1982 were included in this study characterizing AIDS in France. 1) Geographic Trends: Europe (France) (IB4) 1B4-Bou-17 [. Prevalence and Spread of AIDS/HTLV-III/LAV B. Geographic and Regional Trends 5. Africa Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Quinn, Thomas C.; Mann, Jonathan M.; Curran, James W.; Piot, Peter. AIDS in Africa: An Epidemiologic Paradigm. Science, 21 November 1986, Vol. 234: 955-963. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland (Quinn); Control Program on AIDS, World Health Organization, Geneva, Switzerland (Mann); AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Curran); Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium (Piot). Initial surveillance studies in central Africa suggest an annual incidence of AIDS of 550 to 1,000 cases per 1,000,000 adults. The male-to-female ratio of cases is 1:1, with higher rates for females under 30 years of age and males over age 40. Clinically, AIDS in Africans is often characterized by a syndrome of diarrhea and weight loss, by opportunistic infections, or by disseminated Kaposi's sarcoma. From 1% to 18% of healthy blood donors and pregnant women and as many as 27% to 88% of female prostitutes have antibodies to human immunodeficiency virus (HIV). The present annual incidence of infection is approximately 0.75% among the general population of central and eastern Africa. The disease is transmitted predominantly by heterosexual activity, blood transfusions, unsterilized needles, and perinatally from infected mothers to their newborns and will continue to spread rapidly where economic and cultural factors favor these modes of transmission. Prevention and control of HIV infection through educational programs and blood bank screening should be an immediate public health priority for all African countries. This classic article was a review of current literature on the epidemiology of AIDS in Africa. Surveillance data are reported. Rate estimates are based on surveillance data from the World Health Organization Collaborating Center on AIDS and data from several previous studies and from ongoing prospective serosurveys of selected populations in Nairobi, Kenya, and Kinshasa, Zaire. 1) Geographic Trends: Africa (IB5) 1B5-Qui-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Mann, Jonathan M., MD, MPH; Francis, Henry, MD; Davachi, Farzin, MD, FAAC, FAAP, FACA; Baudoux, Paola, MD; Quinn, Thomas C., MD; Nzilambi, Nzila, MD; Bosenge, Ngaly, MD; Colebunders, Robert L., MD; Kabote, Ndoko, MD; Piot, Peter, MD, PhD; Asila, Pangu Kaza, MD, MPH; Curran, James W., MD, MPH. Human Immunodeficiency Virus Seroprevalence in Pediatric Patients 2 to 14 Years of Age at Mama Yemo Hospital, Kinshasa, Zaire. Pediatrics, October 1986, Vol. 78, No. 4: 673-677. Projet SIDA, Department of Public Health, Kinshasa, Zaire; AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland; Mama Yemo Hospital, Kinshasa, Zaire; Institute of Tropical Medicine, Antwerp, Belgium. In a study of prevalence of antibody to to human immunodeficiency virus (HIV) conducted among 368 children in Kinshasa, Zaire, 40 (11%) children were HIV seropositive. Only | of 92 (1%) healthy siblings of these patients was seropositive. Seropositivity was associated with previous hospitalization, receipt of blood transfusion prior to current hospitalization, receipt of medical injections during the past year, and smaller household size. Clinical diagnoses of malnutrition and pneumonia were associated with seropositivity, with a spectrum of diagnoses that resembled those of children with HIV infection in the United States. A higher proportion of seropositive children died during the current hospitalization (4 of 40 seropositive children versus 10 of 328 seronegative children); when patients with malaria were excluded, the in- hospital mortality of seropositive children was more than eight times higher than that of seronegative children. Clarification of the clinical, immunologic, and epidemiologic features of childhood HIV infection, which appears to account for or complicate a substantial proportion of pediatric hospitalizations in Kinshasa, is urgently required. A standardized questionnaire was given to all study participants to obtain demographic information and histories of exposure to blood, needles, and other instruments (through transfusions, injections, vaccinations, acupuncture, or scarifications) and prior hospitalizations. Seroprevalence was determined by testing for antibody to HIV by enzyme-linked immunoassay, with confirmation by Western blot. Children 2 to 14 years of age admitted to the pediatric service at Mama Yemo Hospital in Kinshasa, Zaire, from 1 November 1984 through 31 March 1985 were eligible for this study. Completed questionnaires and sera were available for 368 children (of 852 hospitalized during the study period). In addition, 92 healthy siblings were enrolled from the 288 patient households having siblings of the appropriate age. The study excluded many severely ill children and several recognized pediatric AIDS cases. 1B5-Man-2 Policy Keys: 1) Geographic Trends: Africa (Zaire) (IB5), 2) Populations: Pediatric Cases (IA4), 3) Clinical Manifestations (Pediatric) (IIIA4) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Wendler, I.; Schneider, J.; Gras, B.; Fleming, A.F.; Hunsmann, G.; Schmitz, H. } Seroepidemiology of Human Immunodeficiency Virus in Africa. British Medical Journal, 27 September 1986, Vol. 293: 782-785. Deutsches Primatenzentrum, Gottingen, Federal Republic of Germany (Wendler, Schneider, Hunsmann); Bernhard Nocht Institut, Hamburg, Federal Republic of Germany (Gras, Schmitz); Tropical Diseases Research Centre, Ndola, Zambia (Fleming). Serum samples from 6,015 central African subjects without symptoms of AIDS or contact with the disease were examined for antibodies to human immunodeficiency virus (HIV). Serum samples had been collected between 1976 and 1984. Although 9.3% of the samples tested by enzyme-linked immunosorbent assay (ELISA) were positive, only 4 of 6,015 (0.07%) were confirmed positive by radioimmunoprecipitation or immunofluorescence. Three of these four were from Gabon and one was from Senegal. By contrast, two samples from six AIDS suspects from Guinea-Bissau and all samples from 13 patients with AIDS in Kinshasa, Zaire, and from two of three contacts of those patients were positive for HIV. All these samples were collected during 1985. The authors conclude that the high prevalence of antibodies to HIV reported in tropical Africa by other researchers was probably the result of nonspecific reactions on the enzyme-linked immunosorbent assay (ELISA) and of high levels of antimalarial and other antibodies and immune complexes. Previous researchers who had found a high prevalence of seropositivity in rural Africa suggested an African origin for HIV. The results here do not support that conclusion. On the contrary, they show that the virus has not been endemic in rural areas of sub-Saharan Africa until recently. An ELISA was used to test 2,573 serum samples. Positive samples were reexamined by immunoprecipitation. Another 3,464 samples were tested by indirect immunofluorescence, and positives were also reexamined by immunoprecipitation. Serum samples from 6,015 African subjects without symptoms of AIDS or contact with the disease were collected between 1976 and 1984 in Senegal (789), Liberia (935), Ivory Coast (1,195), Burkina Faso (299), Nigeria (536), Gabon (1,649), Zaire (15), Uganda (164), and Kenya (433). In addition, 22 specimens collected in 1985 consisted of samples from 6 AIDS suspects from Guinea-Bissau, 13 AIDS patients from Zaire, and 3 of the Zairans' sexual contacts. 1) Geographic Trends: Africa (IB5) 1B5-Wen-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Mann, Jonathan M., MD, MPH; Francis, Henry, MD; Quinn, Thomas, MD; Asila, Pangu Kaza, MD, MPH; Bosenge, Ngaly, MD; Nzilambi, Nzila, MD; Bila, Kapita, MD; Tamfum, Muyembe, MD; Ruti, Kalisa, MD; Piot, Peter, MD; McCormick, Joseph, MD; Curran, James W., MD, MPH. Surveillance for AIDS in a Central African City: Kinshasa, Zaire. Journal of the American Medical Association, 20 June 1986, Vol. 255, No. 23 3255-3259. Project SIDA (Mann, Francis, Bosenge, Nzilambi), Ministry of Health (Ruti), Mama Yemo Hospital (Asila, Bila), and University of Kinshasa School of Medicine (Tamfum), Kinshasa, Zaire; Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Mann, McCormick, Curran); National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (Francis, Quinn); Institute of Tropical Medicine, Antwerp, Belgium (Piot). Surveillance for AIDS’/in Kinshasa, Zaire, was initiated in July 1984. During the first 8 months, 332 patients met the Centers for Disease Control (CDC) definition for AIDS. Sera from 295 of these patients were available, and 99% of these had antibodies to human T-cell lymphotropic virus type III (HTLV-II). The male-to-female ratio was l:l.l; the mean age of patients was 33.6 years; and the men were significantly older than the women. The estimated incidence rate for adults in Kinshasa is 380 cases per | million people per year. Peak age-specific incidence rates for men and women occurred among the 30- to 39-year age group, although the rate for men in this age group was 24% higher than for women. A reasonable estimate of the current annual incidence of AIDS is thought to be 550 to 1,000 cases per | million people. Testing was done of all potential AIDS patients, and epidemiologic fea- tures of the infected population are described. Lymphocyte subtyping was performed with OKT3, OKT4, and OKT& monoclonal antibodies. Blood sera were tested for antibody to HTLV-II by enzyme-linked immunosorbent assay (ELISA) and by Western blot analysis; specimens were considered positive if reactive on two separate ELISAs, and confirmed by Western blot. From among 565 cases of suspected AIDS in Kinshasa, Zaire, the first 332 AIDS patients were detected during the first 8 months (October 1983 through May 1984) of this surveillance study. 1) Geographic Trends: Africa (Zaire) (IB5) 1B5-Man-4 Author(s) Title: Source: Institution: Findings: Method: de-The, G.; Gessain, A.; Gazzolo, L.; Robert-Guroff, M.; Najberg, G.; Calender, A.; Peti, M'Pangi; Brubaker, G.; Bensliman, A.; Fabry, F.; Strobel, M.; Robin, Y.; Fortune, R. Comparative Seroepidemiology of HTLV-I and HTLV-II in the French West Indies and Some African Countries. Cancer Research, September 1985, Vol. 45 (Suppl.): 4633s-4636s. Laboratory of Epidemiology and Immunovirology of Tumors, Faculty of Medicine A. Carrell, Lyon, France (de The, Gessain, Gazzolo, Najberg, Calender); Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Roberg-Guroff, Najberg); National Institute of Hygiene, Warsaw, Poland (Najberg); Hopital Compagnie Sucriere, Kwilu Ngongo, Zaire (Peti); Shirati Hospital, Private Bag, Musoma, Tanzania (Brubaker); Hopital Militaire Avicenne, Service d'Immunologie, Marrakech, Morocco (Bensliman); Centre Hospitalier Lyon-Sud, Unite d'Hygiene et Epidemiologie, Pierre-Benite, France (Fabry); D.D.A.S.S., Cayenne, French Guyana (Strobel); Institut Pasteur de la Guyane Francaise, Cayenne, French Guyana (Robin); and Government Laboratory of Health Service, Island of Dominica (Fortune). The prevalence of human T-cell lymphotropic virus type I (HTLV-I) and HTLV-II seropositivity was studied in a comparative survey in the French West Indies and African countries. The data confirm that HTLV-I antibody prevalence varied from 3.4% to 5.2% among blood donors and increased with age to reach a value of 33.3% among elderly people from the Dominica island. Of the French West Indies ethnic groups tested, seropositivity to HTLV-I ranged from 3.3% (Carib Indians) to 13.4% (Boni blacks). Seropositivity to HTLV-II was 3.1% for Haitians from 20 to 39 years of age, the highest for any group in the French West Indies. From this study, HTLV-I antibody prevalence in African countries appears to shift regionally. North African regions are mostly seronegative (Morocco, 0.6%; Upper Volta, 4.6%); the Sudanic region shows an intermediate gradient (south Sudan, 9.2%; northeast Uganda, 8.0%); and equatorial Africa shows the highest seropositivity (south Zaire, 14.4%; northwest Zaire, 16.9%). HTLV-II was not highly prevalent in North African regions (Morocco, 2.4%), but was prevalent in equatorial Africa (northeast Uganda, 44.8%; south Sudan, 39.5%). As the Ugandan sera were collected between 1972 and 1974, the results suggest that a large part of the Ugandan population was infected with HTLV-III 10 years ago. In the West Indies, serum samples were obtained from blood donors through existing serum banks or from sera collected for other purposes. African sera were obtained from established serum banks and from recent collections. Sera from Uganda and Ivory Coast subjects were collected in the early 1970s. Antibodies to HTLV-I and HTLV-III were tested by an enzyme-linked immunosorbent assay with semipurified virions. 1B5-deT-5 Sample Size: Policy Keys: Sera from the following French West Indies groups were studied: blood donors (age range, 18 to 59 years), including 261 from Martinique, 96 from Dominica, and 582 from French Guyana; older normal individuals, including 153 from Martinique (age range, 60 to 90 years), 30 from Dominica, and 75 from French Guyana. The following French West Indies ethnic groups were studied: 90 Carib Indians (Dominica) and 211 Haitians, 82 Dominican prostitutes, 97 Boni blacks, 57 Wayana Indians, 57 Hmong residents, and 28 Hmong newcomers (French Guyana). Sera from the following African groups were studied: 187 from south Zaire, 468 from northwest Tanzania, 100 from Ivory Coast, 101 from northeast Uganda, 76 from south Sudan, 43 from Upper Volta, and 677 from Morocco. 1) Geographic Trends: Africa, Caribbean (IB5,2), 2) Cofactors: HTLV-I (IC3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Biggar, Robert J.; Melbye, Mads; Kestens, Luc; deFeyter, Marc; Saxinger, Carl; Bodner, Anne J.; Paluko, L.; Blattner, William A.; Gigase, Paul L. Seroepidemiology of HTLV-II Antibodies in a Remote Population of Eastern Zaire. British Medical Journal, 16 March 1985, Vol. 290: 808-810. National Cancer Institute, Bethesda, Maryland (Biggar, Saxinger, Blattner); Institute of Cancer Research, Aarhus, Denmark (Melbye); Institute of Tropical Medicine, Antwerp, Belgium (Kestens, Gigase); FORMULAC Hospital, Katana, Kivu District, Zaire (deFeyter, Paluko); Biotech Research Laboratories Inc., Rockville, Maryland (Bodner). In May 1984, outpatients at a hospital in remote eastern Zaire were surveyed for AIDS-type illnesses and were tested for antibodies to human T-cell lymphotropic virus type III (HTLV-II). No clinical cases of AIDS were diagnosed, and the hospital staff could not recall having seen any patients with AIDS-like features. Overall, 31 (12.4%) of 250 had clearly positive tests for HTLV-II antibody and 30 (12%) had borderline results. The prevalence of antibody was highest among children; among adults, prevalence rose slightly with age. HTLV-II antibodies were more common among the uneducated agricultural workers and among rural residents. One urban resident had strong antibody indications by Western blot analysis. The authors suggest that the relatively high prevalence of antibodies among the rural poor in Zaire indicates that HTLV-II, or a closely related virus, may be endemic in the region. A different natural history of infection, perhaps in childhood, is also hypothesized. This epidemiologic study describes findings in 250 outpatients in an eastern Zaire hospital. Patients were interviewed, measured for height and weight, and asked to donate blood for the study. Antibody testing for HTLV-II by enzyme-linked immunosorbent assay (Western blot analysis on a subset) was also performed. Hospital wards were surveyed for clinical cases fitting the description of AIDS, and medical staff were questioned about their experience with such cases. A total of 250 outpatients at FORMULAC Hospital at Katana, in a remote area of eastern Zaire, were studied in May 1984. Average age was 32 years (range, 8 to 78). Of the total, 140 (56%) were female. Of the 233 adults, 46% were in agricultural jobs, 37% were in other trades, 12% were students, and 5% were unemployed. Of the adults, 41% had no schooling. Two-thirds of the subjects lived in small villages or rural huts, and the rest came from the city of Bukavu. 1) Geographic Trends: Africa (Zaire) (IB5), 2) Cofactors: Demographic Status (IC1) 1B5-Big-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Saxinger, W. Carl; Levine, Paul H.; Dean, A.G.; De The, Guy; Lange- Wantzin, Gunhild; Moghissi, Jasmine; Laurent, Francine; Hoh, Mei; Sarngadharan, M.G.; Gallo, Robert C. Evidence for Exposure to HTLV-III in Uganda Before 1973. Science, | March 1985, Vol. 227: 1036-1038. Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Saxinger, Moghissi, Laurent, Hoh, Sarngadharan, Gallo); Clinical Epidemiology Branch, National Cancer Institute (Levine); International Agency for Research in Cancer, Lyon, France (Dean); Laboratoire d'Epidemiologie et Immunovirologie des Tumeurs, Lyon, France (De The); Bispebjerg Hospital, Copenhagen, Denmark (Lange- Wantzin). Fifty of 75 blood samples collected in the West Nile district of Uganda between August 1972 and July 1973 contained antibodies to human T-cell lymphotropic virus type III (HTLV-II). While the prevalence was high, the antibody levels were relatively low. Twelve of 75 samples were positive in a test for HTLV type [ antibodies. Earlier studies indicated that HTLV-I occurs with high frequency in regions of central Africa, and closely related retroviruses are present in many Old World monkeys. The authors suggest that the virus detected in these blood samples may have been a predecessor of HTLV-III or that it was HTLV-III existing in a population already acclimated to its presence. They suggest that these findings strengthen the theory that Africa is the continent of origin of HTLV-IIIL. Blood samples were tested by enzyme-linked immunosorbent assay for antibody to HTLV-IIl and HTLV-I. Blood samples were donated by clinically healthy donors in a sparsely populated subsistence-farming area who were serving as controls for a 1973 study of Burkitt's lymphoma. The mean age of the patient population was 6.4 years. 1) Geographic Trends: Africa (Uganda) (IB5), 2) Cofactors: HTLV-I (IC3) 1B5-Sax-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Brun-Vezinet, F.; Rouzioux, C.; Montagnier, L.; Chamaret, S.; Gruest, J.; Barre-Sinoussi, F.; Geroldi, D.; Chermann, J.C.; McCormick, J.; Mitchell, S.; Piot, P.; Taelman, H.; Mirlangu, Kapita Bila; Wobin, Odio; Mbendi N.; Mazebo P.; Kalambayi, Kayembe; Bridts, C.; Desmyter, J.; Feinsod, F.M.; Quinn, T.C. Prevalence of Antibodies to Lymphadenopathy-Associated Retrovirus in African Patients with AIDS. Science, 26 October 1984, Vol. 226: 453-456. Hopital Claude Bernard, Paris, France (Brun-Vezinet, Rouzioux); Viral Oncology Unit, Institut Pasteur, Paris, France (Montagnier, Chamaret, Gruest, Barre-Sinoussi, Geroldi, Chermann); Centers for Disease Control, Atlanta, Georgia (McCormick, Mitchell); Institute of Tropical Medicine, Antwerp, Belgium (Piot, Taelman); Mama Yemo Hospital, Kinshasa, Zaire (Mirlangu); University Hospital, University of Kinshasa, Zaire (Wobin, Mbendi, Mazebo, Kalambayi); University of Antwerp, Antwerp, Belgium (Bridts); Rega Institute, University of Leuven, Leuven, Belgium (Desmyter); National Institute of Allergy and Infectious Disease, Bethesda, Maryland (Feinsod, Quinn). Antibody testing for lymphadenopathy-associated virus (LAV) was performed on Zairian patients with AIDS in 1983. By two different tests, 35 of 37 patients (94%) and 32 of 36 patients (88%), respectively, were positive for LAV antibodies. In a control group of 26 patients, 6 (23%) were positive. Of these six control patients, five had clinically demonstrable infectious diseases and low helper/suppressor T-cell ratios. In addition, 5 of 100 blood sera collected from a control group of Zairian mothers in 1980 were positive for LAV. Other evidence suggests that LAV was present in Zaire in central Africa as early as 1977. In this case-control study, antibody testing for LAV was performed by enzyme-linked immunosorbent assay and radioimmunoprecipitation assay in parallel. A total of 37 AIDS patients from Zaire were studied. Control groups included 26 other patients treated at Mama Yemo and University Hospitals in Kinshasa, Zaire, 100 Zairian mothers who had participated in hepatitis B studies in 1980, and another group of 100 patients with noninfectious disease treated at a hospital in Kinshasa, Zaire, in 1983. 1) Geographic Trends: Africa (Zaire) (IB5) 1B5-Bru-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Piot, Peter; Taelman, Henri; Minlangu, Kapita Bila; Mbendi, N.; Ndangi, K.; Kalambayi, Kayembe; Bridts, Chris; Quinn, Thomas C.; Feinsod, Fred M.; Wobin, Odio; Mazebo, P.; Stevens, Wim; Mitchell, Sheila; McCormick, Joseph B. Acquired Immunodeficiency Syndrome in a Heterosexual Population in Zaire. The Lancet, 14 July 1984, Vol. 2, No. 8394: 65-69. Institute of Tropical Medicine, Antwerp, Belgium; Mama Yemo Hospital, Kinshasa, Zaire; University Hospital, University of Kinshasa, Zaire; National Instutite of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; University of Antwerp; Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. This study reports the clinical, immunological, and epidemiological features of 38 AIDS patients identified in Kinshasa, Zaire, during a 3- week period in 1983. The male-to-female ratio was l.l:l; the annual rate for Kinshasa was estimated to be at least 17 cases per 100,000 population. Opportunistic infections were diagnosed in 84% of patients. Immunological characteristics of patients were similar to those reported in U.S. AIDS patients, and immunological abnormalities were also found in six controls with infectious diseases (tuberculosis) but with no symptoms of AIDS. Female AIDS patients were younger than male patients and were more often single. Homosexuality, drug abuse, and blood transfusion did not appear to be risk factors for any of these patients. These findings strongly indicate the potential for heterosexual transmission of AIDS. This case-control study compared the clinical status and immunological blood test results of recently admitted AIDS patients at two large and two small hospitals with findings for a matched control group of other patients. Thirty-eight AIDS cases were reported in hospitals in Zaire during a 3- week period in 1983; 26 controls were selected from patients on the same wards as the cases, patients undergoing elective surgery, and patients at a tuberculosis clinic. Geographic Trends: Central Africa (Zaire) (IB5), 2) Transmission: Sexual Activity (IIA), 3) Populations: Heterosexuals (IA6) 1B5-Pio-9 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Van de Perre, Philippe; LePage, Philippe; Kestelyn, Philippe; Hekker, Anton C.; Rouvroy, Dominique; Bogaerts, Jos; Kayihigi, Joseph; Butzler, Jean-Paul; Clumeck, Nathan. Acquired Immunodeficiency Syndrome in Rwanda. The Lancet, 14 July 1984, Vol. 2, No. 8394: 62-64. Saint-Pierre University Hospital, Brussels, Belgium; Centre Hospitalier de Kigali, Rwanda; National Institute of Public Health and Environmental Hygiene, Bilthoven, Netherlands. Kaposi's sarcoma is endemic in Rwanda. During a 4-week period, 26 AIDS patients (17 male, 9 female) were diagnosed and identified in the capital city through physicians' reports as having clinical evidence of opportunistic infections, Kaposi's sarcoma (KS), or pre-AIDS syndrome. Sixteen patients had opportunistic infections, associated with KS in only two; one had multifocal KS alone; and nine had clinical conditions consistent with pre-AIDS. All patients had severe T-cell defects, with a striking decrease in the helper T-cell count. Twenty-one of 22 urban patients lived in urban areas, and many were middle or upper class. Most of the men were promiscuous heterosexuals, and 43% of the females were prostitutes. No patient had a history of homosexuality, intravenous drug abuse, or tranfusion in the previous 5 years before the study. The authors suggest that AIDS is present in central Africa as an entity probably unrelated to the well-known endemic African KS. An association of urban environment, relatively high income, and heterosexual promiscuity could be risk factors for AIDS in Africa. Case reports were done of 26 Rwandan AIDS patients in a prospective study. Twenty-six AIDS patients (17 male, 9 female) were diagnosed in Kigali, Rwanda, and identified through physicians' reports as having clinical evidence of opportunistic infection, Kaposi's sarcoma, or pre-AIDS syndrome. 1) Geographic Trends: Africa (Rwanda) (IB5), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (Il[Al), 3) Populations: Heterosexuals, Prostitutes (IA6) 1B5-Van-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Clumeck, Nathan, MD; Sonnet, Jean, MD; Taelman, Henri, MD; Mascart- Lemone, Francoise, MD; De Bruyere, Marc, MD; Vandeperre, Philippe, MD; Dasnoy, Jean, MD; Marcelis, Luc, MD; Lamy, Monique, MD; Jonas, Claude, MD; Eyckmans, Luc, MD; Noel, Henri, MD; Vanhaeverbeek, Michel, MD; Butzler, Jean-Paul, MD. Acquired Immunodeficiency Syndrome in African Patients. The New England Journal of Medicine, 23 February 1984, Vol. 310, No. 8: 492-497. Division of Infectious Diseases, Department of Medicine, and the Departments of Immunology and Microbiology, Saint-Pierre Hospital, Brussels; Departments of Medicine, Hematology, Virology and Pathology, Saint-Luc Hospital, Brussels; Department of Medicine, Institute of Tropical Diseases, Antwerp; Department of Medicine, Brugmann Hospital; Department of Medicine, Anderlecht Hospital, Brussels, Belgium. Eighteen previously healthy African patients living in Europe were hospitalized in Belgium between 1979 and 1983 with opportunistic infections, Kaposi's sarcoma, or both. Ten died. During the same period five other patients were hospitalized with prodromal AIDS (chronic lymph node disease, fever, weight loss, and diarrhea). All patients tested had a marked decrease in helper T cells and an inversion of the normal ratio of helper to suppressor T cells. There was no evidence of an underlying immunosuppressive disease and no history of blood product transfusion, homosexuality, or intravenous or inhalant drug abuse. This syndrome in patients originally from central Africa is similar to AIDS reported in American patients, but risk factors vary dramatically. Case reports of 20 patients (15 with AIDS and 5 with prodromal illness) were studied prospectively and questioned with the detailed standardized questionnaire developed by the Centers for Disease Control. A case- control method was used for immune cell studies. Eighteen previously healthy African patients (12 men aged 28 to 56 with a mean of 38 years and six women aged 23 to 37 with a mean age of 28 years) and five with a pre-AIDS syndrome (three women with a mean age of 28 years and two men with a mean age of 47 years) were studied; the AIDS patients were all hospitalized with Kaposi's sarcoma or opportun- istic infections. The control group for immune cell studies consisted of 20 age- and sex-matched black Africans residing in Belgium who were not known to be drug abusers or homosexuals. 1) Geographic Trends: Africa (IB5), 2) Immunological Aspects (IIIE) 1B5-Clu-11 I. Prevalence and Spread of AIDS/HTLV-III/LAV B. Geographic and Regional Trends 6. Asia Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Hattori, Toshio; Robert-Guroff, Marjorie; Chosa, Toru; Matsuoka, Masao; Yamaguchi, Kazunari; Ishii, Toshinori; Gallo, Robert C.; Takatsuki, Kiyoshi. Natural Antibodies in Sera from Japanese Individuals Infected with HTLV-I Do Not Recognize HTLV-IIIL. Blood, September 1985, Vol. 66, No. 3: 745-747. Second Department of Internal Medicine, Kumamoto University Medical School, Japan; Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland. In an effort to clarify relationships of the human T-cell lymphotropic virus (HTLV) subgroups, this study was conducted to determine whether antibodies to HTLV-I react with HTLV-II. Of 71 blood sera from Japanese individuals seropositive for HTLV-I, six samples reacted with HTLV-II in the enzyme-linked immunosorbent assay (ELISA), but these sera did not react specifically with HTLV-Ill-related proteins (pl5, p24, or gp4l) when analyzed by Western blot. There is very little seropositivity to HTLV-I in the U.S. Results indicate that coincidental infection with HTLV-I and HTLV-II in Japan is very rare and that HTLV- [IT is not naturally prevalent in Japan. This laboratory study examined sera for antibodies to HTLV-I by indirect immunofluorescence and to HTLV-IIl by an ELISA and a strip radio- immunoassay based on Western blot techniques. Blood sera from 71 Japanese subjects infected with HTLV-I living in southwestern Japan were studied: 23 healthy carriers and 48 patients, including 18 with smoldering adult T-cell leukemia (ATL), 13 with chronic ATL, and 17 with acute ATL. (HTLV-II is endemic in south- western Japan.) Also studied were sera from 24 patients with aplastic anemia (congenital deficiency of oxygen-bearing blood components). 1) Geographic Trends: Asia (SW Japan) (IB6), 2) Cofactors: HTLV-I (IC3) 1B6-Hat-1 I. Prevalence and Spread of AIDS/HTLV-III/LAV C. Cofactors 1. Demographic Status (age, sex, ethnicity) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Mayer, Kenneth H., MD; Ayotte, David, MSPH; Groopman, Jerome E., MD; Stoddard, Anne M., ScD; Sarngadharan, Mangalasseril, PhD; Gallo, Robert, MD. Association of Human T Lymphotropic Virus Type III Antibodies with Sexual and Other Behaviors in a Cohort of Homosexual Men from Boston with and without Generalized Lymphadenopathy. The American Journal of Medicine, March 1986, Vol. 80: 357-363. Fenway Community Health Center, New England Deaconess Hospital and Harvard Medical School, Boston, Massachusetts; University of Massachusetts Division of Public Health, Amherst, Massachusetts; Litton Bionetics, Inc., Kensington, Maryland; National Cancer Institute, Bethesda, Maryland; Memorial Hospital, Pawtucket, Rhode Island; Brown University, Providence, Rhode Island. In this study, the relationship between lifestyle, clinical conditions, and serologic evidence of human T-cell lymphotropic virus type [II (HTLV-II) exposure in a cohort of homosexual men was examined. Subjects who had antibodies to HTLV-III included 20% of the asymptomatic men and 92% of those with lymphadenopathy. None of the men had subsequently developed AIDS at the time of this report (submitted July 1985). Positive tests for HTLV-II were associated with receptive anal intercourse, oral exposure to ejaculate, and a history of hepatitis B, anal gonorrhea, or intestinal parasites, but no other sexually transmitted diseases or use of recreational drugs. Positive tests were more common in men with multiple partners from New York City and less evident in relation to the number of partners from San Francisco or Los Angeles. (The whole cohort generally had fewer contacts with men from these western cities.) Based on these findings, the authors suggest that risk reduction efforts among homosexual men should focus on decreasing the number of partners, receptive anal intercourse, oral exposure to ejaculate and other intimate rectal contact, and sexual contact with men from areas of increased HTLV-III seroprevalence. Subjects were chosen from patients presenting themselves for sexually transmitted disease screening and judged to be free from AIDS-related illness and from among patients with generalized lymphadenopathy with or without general AIDS-related complaints. All subjects completed a self-administered questionnaire which covered demographic data, specific sexual practices, numbers of lifetime and previous-year sexual contacts, sexually transmitted disease history, AIDS-related symptoms, recreational drug use, known contacts with AIDS victims, and sexual exposure to men from three high-risk cities (New York, Los Angeles, and San Francisco). Blood samples were tested for HTLV-II antibody by enzyme-linked immunosorbent assay, with negative samples retested by Western blot; a positive result on either test was classed as positive. Forty asymptomatic homosexually active Boston men and 39 Boston men with generalized lymphadenopathy were recruited from the Fenway Community Health Center and a medical practice based at the New 1C1-May-1 Policy Keys: England Deaconess Hospital between October 1983 and May 1984. Twelve men classified as having AIDS (by the criteria from the Centers for Disease Control), and 7 asymptomatic homosexual medical providers at the Fenway Community Health Center were also enrolled in the study. 1) Cofactors: Demographic Status, Homosexual Lifestyle (IC1), 2) Risk Reduction: Risk Behaviors and Protection (VA2), 3) Populations: Homosexuals (IA 1) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Goedert, James J.; Biggar, Robert J.; Winn, Deborah M.; Greene, Mark H.; Mann, Dean L.; Gallo, Robert C.; Sarngadharan, M.G.; Weiss, Stanley H.; Grossman, Ronald J.; Bodner, Anne J.; Strong, Douglas M.; Blattner, William A. Determinants of Retrovirus (HTLV-II) Antibody and Immunodeficiency Conditions in Homosexual Men. The Lancet, 29 September 1984, Vol. 2, No. 8405: 711-716. Environmental Epidemiology Branch, Laboratory of Human Carcino- genesis, and Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland; Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland; Biotech Research Laboratories, Inc., Rockville, Maryland; Uniformed Services University of the Health Sciences, Bethesda, Maryland. The relationships among lifestyle, clinical conditions, T-cell subsets, and antibody to human T-cell lymphotropic virus type III (HTLV-II) were monitored in a cohort of 66 homosexual men at high risk for AIDS. HTLV-II antibodies were present in 35 subjects (53%) tested in June 1982. One year later, four previously seronegative men had HTLV-II antibodies. In HTLV-III antibody-positive men, AIDS developed at a rate of 6.9% per year, and other clinical signs of immunodeficiency (AIDS- related complex, ARC) at 13.1% per year. All six of the AIDS cases and at least eight of the ten ARC cases showed HTLV-III antibodies 1 week to 21 months before diagnosis. HTLV-IIl antibody was present or acquired in 19 of 24 subjects with stable lymphadenopathy. Lower helper T-cell counts, reflecting patients' immune status, were closely related to HTLV-III seropositivity, even in the 26 healthy subjects with no clinical abnormality. Lifestyle risk factors for HTLV-II seropositivity were a large number of homosexual partners and receptive anal intercourse, with apparent synergistic interaction between these activities. The authors suggest that frequent anal intercourse with many homosexual partners predisposes to HTLV-II infection, with the consequent emergence of lymphadenopathy and various manifestations of lesser and fully developed AIDS. Patients were clinically examined, completed a self-administered questionnaire and were asked to donate blood for laboratory studies. Univariate and multivariate analyses were used to examine the relation- ships among lifestyle, clinical conditions, T-cell subsets, aad antibody to HTLV-II. Subjects were followed up for 2 years for disease development and serum sampling. A cohort of 66 homosexual men at high risk of AIDS who entered the private practice of a general internist in central Manhattan in a 4-day period in June 1982 were followed up for 2 years. 1) Cofactors: Homosexual Lifestyle (ICl), 2) Incubation Period and Disease Stages (IIIC), 3) Transmission: Sexual Activity (IIA), 4) Populations: Homosexuals (IA1) 1C1-Goe-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Jaffe, Harold W., MD; Choi, Keewhan, PhD; Thomas, Pauline A., MD; Haverkos, Harry W., MD; Auerbach, David M., MD; Guinan, Mary E., PhD, MD; Rogers, Martha F., MD; Spira, Thomas J., MD; Darrow, William W., PhD; Kramer, Mark A., PhD; Friedman, Stephen M., MD; Monroe, James M., MS; Friedman-Kien, Alvin E., MD; Laubenstein, Linda J., MD; Marmor, Michael, PhD; Safai, Bijan, MD; Dritz, Selma K., MD; Crispi, Salvatore J., BA; Fannin, Shirley L., MD; Orkwis, John P., BS; Kelter, Alexander, MD; Rushing, Wilmon R., MPH; Thacker, Stephen B., MD; Curran, James W., MD, MPH. National Case-Control Study of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia in Homosexual Men: Part 1, Epidemiological Results. Annals of Internal Medicine, August 1983, Vol. 99, No. 2: 145-151. AIDS Activity, Center for Infectious Diseases, and Epidemiology Program Office, Centers for Disease Control, Atlanta, Georgia; New York City Department of Health; New York University Medical Center; Memorial Sloan-Kettering Cancer Center, New York, New York; Department of Public Health, City and County of San Francisco; Department of Health Services, County of Los Angeles, California. This study evaluates risk factors for the occurrence of Kaposi's sarcoma and Pneumocystis carinii pneumonia in homosexual male patients. Fifty patients with Kaposi's sarcoma and/or P. carinii pneumonia were compared with 120 homosexual male controls matched by age, race, and urban area of residence. The variable most strongly associated with occurrence of the illnesses was a larger number of male sexual partners per year (median: 61 for patients, 27 and 25 for «clinic and private practice controls, respectively). Compared with controls, cases were also more likely to have been exposed to feces during sex, to have had syphilis and non-B hepatitis, to have been treated for parasites of the stomach or bowels, and to have used various illicit drugs. Subjects in this case-control study were interviewed in person by a Centers for Disease Control physician. The same physician interviewed both a patient and his matched controls. Questions asked of the cases concerned the period before the onset of illness; questions for controls were matched for the same period. Topics included sociodemographic characteristics, medical history, occupational and travel history, exposure to toxic substances, use of prescription and illicit drugs, use of inhalant sexual stimulants, sexual history, and family history. Patients were 50 homosexual men between the ages of 21 and 53 years (mean, 35.1 years); 39 had biopsy-proven Kaposi's sarcoma, 8 had P. carinii pneumonia, and 3 had both; 35 were from New York, 9 from San Francisco, 4 from Los Angeles, and 2 from Atlanta. Two groups of control subjects were used: 78 clinic controls (homosexuals from public and private sexually transmitted disease clinics) and 42 private controls (homosexual men selected from the practice of an internist or family physician). All 50 cases had at least one matched control subject, 1Cl-Jaf-3 matched by age, race, and metropolitan area of residence, in one of the two control groups, and 38 cases had controls in both groups. Policy Keys: 1) Cofactors: Homosexual Lifestyle (ICl), 2) Transmission: Sexual Activity (IIA), 3) Populations: Homosexuals (IA) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Rogers, Martha F., MD; Morens, David M., MD; Stewart, John A., MD; Kaminski, Rose M., MS Hyg; Spira, Thomas J., MD; Feorino, Paul M., PhD; Larsen, Sandra A., PhD; Francis, Donald P., MD; Wilson, Marianna, MS; Kaufman, Leo, PhD. National Case-Control Study of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia in Homosexual Men: Part 2, Laboratory Results. Annals of Internal Medicine, August 1983, Vol. 99, No. 2: 151-158. Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. The Centers for Disease Control conducted this case-control study to investigate an outbreak of Kaposi's sarcoma (KS) and Pneumocystis carinii pneumonia in homosexual men. The occurrence of these diseases was found to be associated with certain aspects of lifestyle, including a greater number of male sexual partners per year, exposure to feces during sex, history of hepatitis and syphilis, history of enteric (intestinal tract) parasites, and use of illicit drugs. Laboratory results also reflected this lifestyle pattern and the probable cause of the outbreak of KS and pneumonia -- a cellular immune deficiency. Patients were found to have a deficiency of the helper T-cell subpopulation and lower helper/suppressor T-cell ratios. Patients were also found to have higher levels of antibody to Epstein-Barr virus and cytomegalovirus, higher prevalence of antibody to hepatitis A virus and Treponema pallidum, a lower prevalence of antibody to varicella-zoster virus, and a higher frequency of active cytomegalovirus infection. This case-control study examines cultures, serologic tests and quantitative immunoglobulins for patients for whom one or more matched controls were available. Patients and controls were questioned on sociodemographic status, medical history, occupational and travel history, exposure to toxic substances, use of prescription and illicit drugs, use of inhalant sexual stimulants, sexual history, sexual practices, and family history. Blood serum and urine specimens and throat and rectal swab specimens were collected from most of the patients. A small number of patients were tested for immunologic abnormalities. T-lymphocyte subpopula- tions and B lymphocytes were quantitated by standard procedures. Lymphocyte transformation responses were quantitated with various mitogens and antigens. Levels of immunoglobulins G, A, and M were quantitated by radial immunodiffusion. Serum specimens were tested for antigens of or antibody to cytomegalovirus, herpes simplex virus types | and 2, Epstein-Barr virus, varicella zoster virus, and others. The 52 AIDS patients who were studied included 39 with Kaposi's sarcoma only, 8 with P. carinii pneumonia only, and 5 with both. The patients had a mean age of 35 years (range, 21 to 53 years); 38 were white, 8 black, and 6 Hispanic. Patients had no history of chronic or debilitating diseases. The onset of symptoms occurred from 18 days to 1C1-Rog-4 Policy Keys: 4.6 years (mean, 370 days) before the interview and collection of specimens for this study. For each patient, the study sought to identify four controls matched for age, sex, sexual orientation, race, and metropolitan area of residence, including: a homosexual friend who was not a sexual partner (friend control), 2 ranomly chosen homosexual patients of a venereal disease clinic (clinic controls), and a homosexual patient chosen randomly from the files of several local practicing physicians (private practice controls). The following controls were included and agreed to be interviewed for the study: 23 friend controls, 78 clinic controls, and 42 private practice controls. One or more biologic specimens were obtained from 21 of the 23 friend controls, 65 of the 78 clinic controls, and 38 of the 42 private practice controls. 1) Cofactors: Lifestyle, Immune Deficiency, Other Infections (IC1,3), 2) Transmission: Sexual Activity (IIA), 3) Populations: Homosexuals (IA 1) I. Prevalence and Spread of AIDS/HTLV-III/LAV C. Cofactors 2. Chemical or Drug Exposures (nitrites, other drugs, alcohol) Author(s): Title: Source: Institution: Findings: Method: Stall, Ron, PhD, MPH; McKusick, Leon, PhD; Wiley, James, PhD; Coates, Thomas J., PhD; Ostrow, David G., MD, PhD. Alcohol and Drug Use During Sexual Activity and Compliance with Safe Sex Guidelines for AIDS: The AIDS Behavioral Research Project. Health Education Quarterly, Winter 1986, Vol. 13, No. 4: 359-371. Alcohol Research Group, Medical Research Institute of San Francisco, San Francisco, California; Department of Urban Studies, Rutgers University, New Brunswick, New Jersey (Stall); Division of General Internal Medicine, University of California, San Francisco, California (McKusick, Coates); Survey Research Center, University of California, Berkeley, California (Wiley); Department of Psychiatry, School of Medicine and Institute for Social Research, University of Michigan, Ann Arbor, Michigan (Ostrow). This article describes the association between drug and alcohol use during sexual activity and the performance of sexual acts that carry a high risk of transmitting AIDS. Some homosexual men have been able to minimize their risk of sexual exposure to human T-cell lymphotropic virus type III (HTLV-II) through careful compliance with health education recommendations, while others have been less consistent in restricting their risky behavior. This finding raises the question of whether compliance is less likely under certain circumstances. Cross-sectional analysis revealed that the use of particular drugs during sex, the number of drugs used, and the frequency of combining drugs and sex are all positively associated with risky sexual activity. The retrospective data showed that men who currently abstain from drug use during sexual activity are most likely to have remained at no risk for the sexual transmission of HTLV-III over two measurement periods during the previous year. The men who currently combined drug use with sex were most likely to have a history of high-risk sexual activity over the previous year. About 90% of the men in the cohort study correctly identified safe-sex techniques as of May 1984. Nonetheless, despite numerous health education programs, a significant proportion of gay men had not adopted safe-sex practices as of May 1985. To the extent that high-risk behavior and drug and alcohol use are related, attempts to promote safe sex may need to include educational messages about drinking and drug use during sexual activity as well. The cross-sectional and retrospective character of the data, however, does not permit distinguishing between correlation and causation in the association between drug use and risky sex. Several hypotheses to explain the correlation and their implications on health education efforts are discussed. Data reported in this article are drawn from a 3-year prospective study of the changes in sexual behavior made by gay men in San Francisco in response to the AIDS epidemic. During the May 1985 period of data collection, a set of items was included in the questionnaire which measured alcohol and drug use in combination with sex during the previous month. During both the May 1984 and May 1985 data collection 1C2-Sta-1 Sample Size: Policy Keys: points, a detailed measure of participation during the past 30 days in a wide variety of sexual behaviors was also obtained, allowing an accurate estimate of changes in sexual behavior over time. Homosexual men who completed questionnaires included 151 recruited from bathhouses, 134 from gay bars, 181 who did not frequent gay bars or bathhouses recruited through advertising in local gay newspapers and organizations, and 189 members of monogamous couples who had participated in other investigations. 1) Cofactors: Use of Drugs and Alcohol (IC2), 2) Information/Educa- tion: Risk Behaviors and Protection (VA2), 3) Populations: Homosexuals (IA1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Brown, Lawrence S., Jr., MD, MPH; Evans, Ruppert, EdD; Murphy, Debra, PhD, MPH; Primm, Beny J., MD. Drug Use Patterns: Implications for the Acquired Immunodeficiency Syndrome. Journal of the National Medical Association, 1986, Vol. 78, No. 12: 1145- 1151. Research, Evaluation and Audit Division, Addiction Research and Treatment Corporation, Brooklyn, New York; Department of Medicine, College of Physicians and Surgeons, Department of Socio-medical Sciences, School of Public Health, Columbia University, New York, New York. Needle sharing has been well accepted as a prominent factor in the risk of acquiring AIDS among drug abusers; however, the pathogenesis of the disease might well be influenced by the immunologic status of the host. This study presents the preliminary findings of an ongoing investigation to assess the contribution of an array of behaviors to various indicators of immunologic status among drug users. The results for the 97 subjects investigated demonstrate that immunological abnormalities were greater among those who began drug use at an earlier age and those who used drugs intravenously. A history of hepatitis was reported by 21% of this sample, 5% reported a history of endocarditis, and 9% admitted to a history of tuberculosis (diseases that are well recognized to be disproportionately more prevalent in the drug- addicted), but these were not associated with any significant change in the immunologic variables evaluated. No effect of sexual behavior, volume of alcohol consumed, or hepatitis antibody or antigen status on the immunologic variables studied was detected. Findings do suggest that abnormal liver function may contribute to altered immune status. Medical and drug histories were taken and physical examinations were performed. Routine laboratory evaluation included a complete blood count, serum electrolytes, liver function tests, and urinalysis. Several indirect measures of immunologic function were also used. The study population was composed of 71 male and 26 female patients applying for admission to or currently enrolled in clinics of the Addiction Research and Treatment Corporation in New York City between I January 1986 and 1 March 1986. The age range was 21 to 55 years (mean, 35). The group consisted of 53.6% blacks, 37.1% Hispanics, and a whites. The duration of drug use ranged from 1 to 39 years (mean, 12.6). 1) Cofactors: Immunosuppressive Effects of Illegal Drugs (IC2), 2) Immunological Aspects (IIIE), 3) Populations: LV. Drug Abusers (IA2), 4) Transmission: [.V. Drug Abuse (IIB) 1C2-Bro-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Haverkos, Harry W., MD; Pinsky, Paul F., MPH; Drotman, D. Peter, MD, MPH; Bregman, Dennis J., MS. Disease Manifestation Among Homosexual Men with Acquired Immuno- deficiency Syndrome: A Possible Role of Nitrites in Kaposi's Sarcoma. Sexually Transmitted Diseases, October-December 1985, Vol. 12, No. 4: 203-208. AIDS Activity, Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. Data from three epidemiologic studies conducted by the Centers for Disease Control (CDC) were analyzed to identify risk factors that determine the major manifestations of AIDS. Compared with AIDS patients who have Pneumocystis carinii pneumonia (PCP) only, AIDS patients with Kaposi's sarcoma (KS) and those with both diseases reported a higher number of sexual partners, more recreational drug use, higher incomes, and higher rates of non-B hepatitis. Multivariate analysis showed that, for the KS vs. PCP and both KS and PCP vs. PCP comparisons, total days of nitrite use more significantly differentiated between the disease groups than did any other variable available for analysis. Greater use of nitrites was reported in both groups with KS. The amount of nitrite use was greater for patients with KS and both diseases than PCP alone. This study suggests that the use of nitrite inhalants may be a cofactor in the development of Kaposi's sarcoma. While the authors urge caution in the interpretation of results, they state that the identification of cofactors may define additional opportunities to prevent the development of AIDS. Records of interviews and laboratory results of all homosexual men with KS or PCP or both and their matched controls from the first two case- control studies and a cluster analysis by sexual partners that CDC personnel carried out were reviewed. Two separate analyses were performed: a comparison of AIDS cases by disease manifestation and a comparison of study cases and controls. Analytic methods were directed toward determining whether any factors differentiate among the disease manifestations of AIDS (KS, PCP, and KS plus PCP). Eighty-seven homosexual men with KS and/or PCP who were interviewed by CDC personnel during case-control studies and other investigations were studied to compare cases of AIDS by disease manifestation. Analy- ses of cases and controls matched for age, race, residence, and sexual orientation included 31 KS cases with 54 matched controls; 14 PCP cases with 25 matched controls; and 13 KS and PCP cases with 23 matched controls. Data for all subjects were obtained from previous studies conducted at the CDC. 1) Cofactors: Nitrites and Kaposi's Sarcoma (IC2), 2) Clinical Manifestations: Kaposi's Sarcoma (IIIA) 1C2-Hav-3 I. Prevalence and Spread of AIDS/HTLV-III/LAV C. Cofactors 3. Clinical Descriptors and Conditions (hepatitis B, Epstein-Barr virus, cytomegalovirus, HLA type) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Sumaya, Ciro Valent; Boswell, Richard Neal; Ench, Yasmin; Kisner, Daniel L.; Hersh, Evan M.; Reuben, James M.; Mansell, Peter W.A. Enhanced Serological and Virological Findings of Epstein-Barr Virus in Patients with AIDS and AIDS-Related Complex. The Journal of Infectious Diseases, November 1986, Vol. 154, No. 5: 864- 870. Departments of Pediatrics, Pathology, and Medicine, University of Texas Health Science Center, San Antonio, Texas; Department of Medicine, Wilford Hall U.S. Air Force Medical Center, Lackland Air Force Base, San Antonio, Texas; Departments of Clinical Immunology and Biological Therapy, Cancer Prevention, and Laboratory Medicine, University of Texas System Cancer Center, M.D. Anderson Hospital, Houston, Texas. This study examined the potential involvement of Epstein-Barr virus (EBV) in AIDS and in AIDS-related complex (ARC). Patients with AIDS or ARC showed an enhanced antibody response to a broad spectrum of EBV antigens, large numbers of EBV in secretions from the mouth and throat, and increased lymphoproliferative ability of the peripheral blood compared with a group of normal healthy adults. These findings were similar to those for patients experiencing acute infectious mononucleosis, the prototype, symptomatic, primary EBV infection. Study findings support growing evidence that EBV may have a contribu- tory role in AIDS and ARC. Study results were based on a single or an initial examination, including serological and virological testing, of each subject. Comparisons are presented for four groups: (1) AIDS patients, (2) ARC patients, (3) healthy controls, and (4) controls with infectious mononucleosis. The study group included 30 male patients with AIDS and 31 male patients with ARC. Two control groups were also included. One group consisted of 27 male patients with acute EBV-induced infectious mononucleosis who had participated in an ongoing prospective study of the disease. The other control group consisted of 31 healthy men with an old, currently quiescent EBV infection. Most of the study subjects were residents of San Antonio, Texas. 1) Cofactors: Epstein-Barr Virus (IC3) 1C3-Sum-1 Author(s): Title: Source: Institution: Findings: Method: Boyko, William J., MD, FRCPC; Schechter, Martin T., MD, MSc, PhD; Craib, Kevin J.P., BA, MMath; Constance, Peter, MB, ChB; Nitz, Rod, MD; Fay, Sean, MD; McLeod, Alastair, MD, FRCPC; O'Shaughnessy, Michael, PhD. The Vancouver Lymphadenopathy-AIDS Study: 5. Antecedent Behavioural, Clinical and Laboratory Findings in Patients with AIDS and HIV-Seropositive Controls. Canadian Medical Association Journal, 15 October 1986, Vol. 135: 881- 887. St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia; Division of Viral Studies, Laboratory Centre for Disease Control, Department of National Health and Welfare, Ottawa, Ontario, Canada. To identify behavioral, clinical, and laboratory findings that might be predictive of AIDS in people with antibody to human immunodeficiency virus (HIV), this study prospectively monitored HIV-seropositive people and then compared data for patients who developed AIDS with corres- ponding data for controls serologically positive for HIV selected from the same cohort. The earliest laboratory and clinical data available for the 25 subjects who developed AIDS preceded the diagnosis of AIDS by a mean of 17.5 months (range, | to 36 months). The earliest laboratory and clinical data available for the 80 subjects who were seropositive yet AIDS free as of February 1986 preceded this study by a mean of 16.7 months (range, 12 to 22 months). The earliest data for the AIDS patients showed greater immunologic abnormalities than the earliest data for the non-AIDS patients. Generalized lymphadenopathy was also more fre- quent among the patients in whom AIDS eventually developed than in the AIDS-free controls. Although the AIDS patients had more antecedent symptoms than controls, no individual symptom or combination of symptoms was more frequent in the AIDS group than in the control group. The authors conclude that most lifestyle variables appear to act as exposure factors in HIV infection, but not as cofactors in the development of AIDS. Subjects in this study were not compared for length of seropositivity. Therefore, the differences between the groups may not be predictive in the sense that they indicate increased susceptibility to AIDS; they may merely identify people who are temporally further along in the process. These observations, however, do not alter the fact that for people with HIV infection of indeterminate duration, laboratory abnormalities may prove useful in identifying seropositive people at high risk for AIDS. The Vancouver Lymphadenopathy-AIDS Study monitored 726 homosexual men who were recruited from six primary care practices in central Vancouver between November 1982 and February 1984. Subjects returned for follow-up visits approximately every 6 months. Part five of the study focused on differences between the earliest clinical and laboratory data available for subjects who later developed AIDS and those who did not. 1C3-Boy-2 Sample Size: Policy Keys: The AIDS group consisted of 25 men, 13 with Kaposi's sarcoma or lymphoma and 12 with opportunistic infections. Another 80 men served as seropositive controls and had not developed AIDS as of February 1986, the time of the analysis. 1) Cofactors: Clinical Descriptors and Conditions (IC3), 2) Disease Stages: Predictors of Progression, (IIIC), 3) Precursors of AIDS (IIIB), 4) Transmission: Sexual Activity (IIA) Author(s): Title: Source: Institution: Findings: Rinaldo, Charles R., Jr.; Kingsley, Lawrence A.; Lyter, David W.; Rabin, Bruce S.; Atchison, Robert W.; Bodner, Anne IJ.; Weiss, Stanley H.; Saxinger, W. Carl. Association of HTLV-II with Epstein-Barr Virus Infection and Abnormalities of T Lymphocytes in Homosexual Men. The Journal of Infectious Diseases, October 1986, Vol. 154, No. 4: 556- 561. Departments of Pathology and Medicine, School of Medicine and Presbyterian-University Hospital; Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; Biotech Research Laboratories, Rockville, Maryland; Environmental Epidemiology Branch, Division of Cancer Etiology; Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland. Epstein-Barr virus (EBV) has been postulated to be a cofactor in human T-cell lymphotropic virus type III (HTLV-II) infection because of its almost universal presence in AIDS and AIDS-related patients and its potential immunosuppressive effects. In the present study, serological evidence of prior infection with EBV was found in almost 100% of the homosexual men tested. Of greater significance was that asymptomatic homosexual men underwent frequent reactivation of or reinfection with EBV in the absence of HTLV-III infection. A substantial proportion of HTLV-II antibody-negative men had higher levels of antibody to two kinds of EBV than did heterosexual male controls. Such EBV infections were related to immunologic abnormalities independent of HTLV-II infection. An increase in the number of suppressor T cells was associated with increased levels of antibody to the two kinds of EBV in asymptomatic, HTLV-III-seronegative men. Mean levels of antibody to one kind of EBV were significantly higher in healthy men and patients with lymphadenopathy syndrome who were HTLV-II seropositive than in HTLV-IlI-seronegative homosexual subjects. This finding was not associated with differences in sexual practices. The authors conclude that EBV and HTLV-II may have temporally related immunologic consequences. The cytotoxic component of suppressor T cells, which could be activated in response to EBV or HTLV- [Il infection, may act to inhibit replication of HTLV-II in helper T cells and possibly in EBV-activated B or T cells. In certain individuals, this antiviral immunity may impede HTLV-II infection and prevent significant illness. Some hosts may develop a persistent increase in the volume of T cells in the lymph nodes, manifested in lymphadenopathy syndrome, possibly related to B cell proliferation due to reactivated EBV infection. Whether such interactions are of importance in the development of AIDS remains to be determined. 1C3-Rin-3 Method: Sample Size: Policy Keys: Antibodies to HTLV-II, two kinds of EBV, and cytomegalovirus were measured for each subject. Each subject was also given a brief physical examination for lymphadenopathy and Kaposi's sarcoma. Lymphadeno- pathy syndrome was defined as lymph nodes greater than 1 cm In diameter at two or more contiguous locations outside the groin present for at least 3 months. The study cohort included 64 healthy homosexual and bisexual male volunteers (63 whites and | black) who were solicited by advertisements and public notices. The mean age of this group was 33 years (range, 18 to 60 years). The cohort reported a mean of 34 (range, 0 to 350) different male sex partners in the year before enrollment. Most of the subjects were enrolled into the study by September 1983, while six were enlisted in January and February 1984. Ten homosexual men with lymphadenopathy syndrome were also studied. Controls for laboratory tests were 27 healthy heterosexual men (26 whites and 1 black) with a mean age of 31 years (range, 24 to 52 years). 1) Cofactors: Epstein-Barr Virus (IC3), 2) Immunological Aspects (IIE) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Perrillo, Robert P., MD; Regenstein, Fredric G., MD; Roodman, Stanford T., PhD. Chronic Hepatitis B in Asymptomatic Homosexual Men with Antibody to Human Immunodeficiency Virus. Annals of Internal Medicine, September 1986, Vol. 105, No. 3: 382-383. Veterans Administration Medical Center; Washington University School of Medicine; St. Louis University School of Medicine, St. Louis, Missouri. This report describes the histologic, immunologic, and virologic features in 12 asymptomatic homosexual men with chronic hepatitis B who tested positive for the human immunodeficiency virus (HIV). They are compared with age-matched antibody-negative controls. None of the 12 patients had evidence of AIDS, and all were in good general health. Four men had generalized lymphadenopathy 2 to 5 years earlier, which had resolved. Homosexual men with antibody to HIV had less severe histologic injury than their antibody-negative homosexual and heterosexual controls who also had chronic hepatitis B. These findings suggest that the antibody-positive patients are less immunologically responsive to hepatitis B virus, even in the absence of clinically evident immunodeficiency. This may mean that antibody- positive patients are more difficult to treat for their chronic hepatitis B because of impaired immune responses, defective regulation of viral proliferation, and larger virus populations. These patients are probably more able to infect sexual partners and health care workers with hepatitis B. This case-control study compared asymptomatic homosexual men with chronic hepatitis B and positive antibody tests for HIV with homosexual and heterosexual men with chronic hepatitis B who were not positive for HIV antibody. Tests were performed to determine T-cell function, histologic findings, and DNA polymerase levels (a marker of active viral replication). Twelve homosexual men who were hepatitis carriers and positive for HIV antibody were included in this study. These 12 were compared with 12 HIV-antibody-negative homosexual men and 12 HIV-antibody-negative heterosexual men, all of whom were also hepatitis B carriers. 1) Cofactors: Hepatitis (IC3), 2) Immunological Aspects (IIE), 3) Precursors of AIDS (IIIB) 1C3-Per-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Greenberg, Alan E.; Sulzer, Alexander J.; Schable, Charles A.; Collins, William E.; Nguyen-Dinh, Phuc. Evaluation of Serological Cross-Reactivity Between Antibodies to Plasmodium and HTLV-II[/LAV. The Lancet, 2 August 1986, Vol. 2, No. 8501: 247-248. Malaria Branch, Division of Parasitic Diseases, and AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. Serum samples from 460 patients with present or previous Plasmodium (the causative agent of malaria) infections, high antimalarial antibodies, and no apparent risk of exposure to human T-cell lymphotropic virus type [II (HTLV-II) were tested for HTLV-II antibody. Only one sample, from a 2l-year-old African woman, was strongly positive by enzyme-linked immunosorbent assay (ELISA) and Western blot test. No samples from 100 HTLV-IlI-positive American homosexual men were strongly reactive for antibodies to the four Plasmodium species that infect humans. The authors conclude that exposure to Plasmodium does not result in HTLV-II seropositivity and that HTLV-III antibodies do not strongly cross-react with malarial antibodies. All serum samples were tested for antibodies to Plasmodium by a standard indirect fluorescent antibody technique. An ELISA test kit was used for HTLV-III antibody testing. A sample was considered positive for HTLV-II only if it was also positive by Western blot testing. Test results were presented for each of six different groups. Serum samples were selected from 460 patients with existing or previous Plasmodium infections and no apparent risk of exposure to HTLV-III. All had high antimalarial antibodies. Patients came from six different populations: 78 American travelers whose samples were collected in 1964-74; nine neurosyphilitics with induced Plasmodium falciparum and Plasmodium malariae infections in 1962-63; 351 specimens collected in 1985 from two African and two South American populations with chronic malarial exposure. Specimens were also collected from 100 American homosexual men in 1982-84; these samples were repeatedly positive for HTLV-III antibodies. 1) Cofactors: Clinical Conditions (Malaria) (IC3) 1C3-Gre-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Birx, Deborah L., MD; Redfield, Robert R., MD; Tosato, Giovanna, MD. Defective Regulation of Epstein-Barr Virus Infection in Patients with Acquired Immunodeficiency Syndrome (AIDS) or AIDS-Related Disorders. The New England Journal of Medicine, 3 April 1986, Vol. 314, No. 14: 874-879. Department of Allergy and Immunology, Walter Reed Army Medical Center, Washington, DC; Department of Viral Diseases, Walter Reed Institute of Research, Washington, DC; Division of Biochemistry and Biophysics, Office of Biologics Research and Review, Food and Drug Administration, Bethesda, Maryland. Patients with AIDS acquire undifferentiated B-cell lymphomas that are similar to African Burkitt's lymphoma (a malignant lymphoma often involving facial bones, ovaries, and abdominal lymph nodes) and contain Epstein-Barr virus. This study found that in test tube assays of immunological function, B cells from seven AIDS patients and 10 AIDS- related complex (ARC) patients produced abnormally low numbers of immunoglobulin-secreting cells (compared with normal controls) and that T-cell suppression of immunoglobulin-secreting cell production, which was greater than 80% in normal controls positive for Epstein-Barr virus, was absent in AIDS and ARC patients. Instead, these patients' T cells showed markedly increased immunoglobulin production induced by Epstein-Barr virus. Patients with AIDS or ARC may be predisposed to the development of lymphomas containing Epstein-Barr virus because they have a profound defect of T-cell immunity to this virus and abnormally high numbers of B cells infected by this virus in their circulatory systems. Unseparated mononuclear cells and cell subsets enriched for B and T cells were purified from peripheral blood by standard techniques. Testing for Epstein-Barr virus-induced nuclear antigen, for the HTLV-III- related antigen P-15, and for cell surface determinants was performed by immunofluorescence, with the use of appropriate human serum samples and monoclonal antibodies. Seven AIDS patients and 10 ARC patients were studied, along with 18 age-matched normal controls. All AIDS and ARC patients had antibodies to HTLV-II. All patients and all controls had antibodies to Epstein-Barr virus. 1) Cofactors: Epstein-Barr Virus (IC3), 2) Immunological Aspects (IIE) 1C3-Bir-6 Author(s): Title: Source: Institution: Findings: Method: Daul, Carolyn Beach, MD, PhD; deShazo, Richard D., MD; Andes, W. Abe, MD; Pankey, G.A., MD. Immunologic Studies in Homosexual and Hemophiliac Subjects with Persistent Generalized Lymphadenopathy: A Comparative Analysis. Journal of Allergy and Clinical Immunology, February 1986, Vol. 77, No. 2: 295-301. Herbert F. Harvey Laboratory, Clinical Immunology Section, and Section of Hematology/Oncology, Departments of Medicine and Pediatrics, Tulane University School of Medicine, New Orleans; Oschner Medical Institutions, New Orleans, Louisiana. A group of male homosexuals and a group of hemophiliacs, each group including some cases of persistent generalized lymphadenopathy, were compared in this study to establish whether similar mechanisms of immune dysfunction are operative in both groups, which have quite different risk factors for AIDS. The eight homosexual men without lymphadenopathy had decreased percentages of helper T cells, increased percentages of suppressor T cells, and low helper/suppressor T-cell ratios, but these results were not significantly different from those for the control subjects. The same immunologic measures were abnormal in both the hemophiliacs and the 10 homosexual subjects with lymphadeno- pathy. Within each group, individuals with lymphadenopathy had more T- lymphocyte subpopulation abnormalities than asymptomatic individuals, but again these differences were not significant. Lymphocyte proliferative responses were significantly depressed in all patient groups compared with control responses. The responses of the hemophiliacs with and without lymphadenopathy were not significantly different, whereas the homosexual group with lymphadenopathy had significantly lower responses than the asymptomatic homosexuals and the lowest responses of all groups. Hemophiliac subjects without lymphadenopathy were the only group aside from the controls that displayed a significant correlation between helper/suppressor T-cell ratio and lymphocyte proliferative response, although the same trend was present in all groups. Homosexual subjects had lower mitogenic responses than would be expected for their helper/suppressor T-cell ratios compared with control subjects and hemophiliacs. These findings suggest that additional factors may be operative in the mononuclear cell populations of homosexual subjects that depress lymphocyte function. These factors may help to explain the higher incidence of AIDS in homosexual subjects than in hemophiliac patients. Peripheral blood mononuclear cells were isolated and enumerated by standard methods. T-lymphocyte populations and subsets were identified by OKT11, OKT4, and OKT& monoclonal antibodies. Cells bearing HLA- DR and a natural killer cell-associated antigen (Leu7) were also identified with monoclonal antibodies. These studies were performed by direct immunofluorescence. Lymphocyte proliferation of &4-day-old mononuclear cell cultures containing phytohemagglutinin were also evaluated. Findings were presented for cases and controls. 1C3-Dau-7 Sample Size: Policy Keys: Subject groups consisted of 18 male homosexuals and 26 factor VIII- deficient hemophiliacs. The homosexuals had a mean age of 33 years, were residents in the New Orleans area, and referred themselves or requested evaluation for possible AIDS; all were sexually active, and most had had multiple sexually transmitted diseases in the past. None were clinically ill at the time of study, but 10 were diagnosed as having persistent, generalized lymphadenopathy, defined as lymphadenopathy for 3 months or longer in two or more sites outside the groin. The hemophiliacs had a mean age of 30 years and were studied while attending the Louisiana Comprehensive Care Hemophilia Center in New Orleans; all patients had used lyophilized (freeze-dried) factor VIII clotting concentrates for 4 years or more; all appeared to be in good health, but 10 were diagnosed as having persistent, generalized lymphadenopathy as discussed above. Twenty-four age-matched, healthy male volunteers served as controls. 1) Cofactors: Immunologic Status (IC3), 2) Precursors of AIDS: Lymphadenopathy (IIIB), 3) Populations: Homosexuals, Hemophiliacs (IA 1,3), 4) Immunologic Aspects, (IIE) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Halbert, Seymour P.; Kiefer, David J.; Friedman-Kien, Alvin E.; Poiesz, Bernard. Antibody Levels for Cytomegalovirus, Herpes Simplex Virus, and Rubella in Patients with Acquired Immune Deficiency Syndrome. Journal of Clinical Microbiology, February 1986, Vol. 23, No. 2: 318-321. Cordis Laboratories, Miami, Florida (Halbert, Kiefer); New York University Medical Center, New York, New York (Friedman-Kien); State University of New York and Veterans Administration Medical Center, Syracuse, New York (Poiesz). This study was undertaken to determine more precisely the quantitative range of cytomegalovirus (CMV) antibody levels in AIDS patients compared with levels found in controls; the scope of the study was expanded to include another virus characterized by latency, herpes simplex virus (HSV), and one which is not, rubella virus (German measles). Significantly higher proportions of patients with AIDS or lymphadenopathy syndrome (LAS) were found to be positive for antibod- ies to CMV and HSV compared with control groups of commercial blood donors. No differences were found in incidence of antibodies to rubella virus in these groups. The entire distribution of antibody concentrations to CMV and HSV in AIDS patients was shifted upward, indicating hy- peractive humoral immune responses to these viruses. But antibody levels for rubella virus showed the same distribution as for controls. No correlation was found between CMV and HSV antibody concentrations in individual AIDS and LAS patients. This was a case-control study in which CMV and HSV antibody determinations were carried out by standardized enzyme immunoassays (Cordis Labs). Sera from a total of 66 patients with AIDS or LAS were compared with sera from a total of 612 controls. Case samples were available from #41 patients who had AIDS with Kaposi's sarcoma, 15 who had AIDS with opportunistic infections, and 10 who had LAS. Control sera were from healthy commercial blood donors in Florida, matched for age and sex to the AIDS group. An additional group of control sera available from the Michigan State Health Department had previously been assayed for rubella virus antibodies; they were obtained primarily from young adult women being screened for rubella-immune status. 1) Cofactors: CMV or Herpes Simplex Virus (IC3) 1C3-Hal-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Ranki, Annamari; Valle, Sirkka-Liisa; Antonen, Jaakko; Suni, Jukka; Jokipii, Liisa; Jokipii, Anssi M.M.; Saxinger, Carl; Krohn, Kai. Immunosuppression in Homosexual Men Seronegative for HTLV-IIIL. Cancer Research, September 1985, Vol. 45 (Suppl.): 4616s-4618s. Departments of Dermatology (Ranki, Valle), Serology and Bacteriology (Jokipii, Jokipii), University of Helsinki, Helsinki, Finland; Institute of Biomedical Sciences, University of Tampere, Tampere, Finland (Antonen, Krohn); Aurora Hospital, Helsinki, Finland (Suni); Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Saxinger). The backgrounds of homosexual men with immunological abnormalities were studied and related to susceptibility to human T-cell lymphotropic virus type [II (HTLV-II) infection. In a cohort of male homosexual men in Finland, 90% were HTLV-III antibody negative. Of these seronegative cases, 10% showed decreased helper/suppressor T-cell ratios. In this immunosuppressed group, more signs of opportunistic infections and AIDS-related complex (ARC) were apparent than in other HTLV-III- negative subjects. During a l6-month follow-up period, four seronegative cases converted to a positive HTLV-II antibody status; three of these had immunosuppression as well. The authors conclude that persons showing in vitro immunosuppression are more susceptible to HTLV-II infection or that alteration in T-cell subsets signals a pre- antibody-positive early phase of HTLV-III infection. This follow-up study, which was started in summer 1983, included immunologic and antibody testing of homosexual men. Every 3 to 6 months the subjects were given a physical examination and an interview which included questions about sexual practices. Antibodies to HTLV-II were assessed by an enzyme immunoassay and confirmed by the Western blotting method. Immunologic studies, including the determination of blood lymphocyte subsets and their in vitro responses to certain mitogens and antigens, were performed. Helper and suppressor T cells were determined with monoclonal antibodies. Antibodies to a panel of common viruses were also measured, and fecal samples were examined for intestinal parasites. A group of 200 male homosexual volunteers in Finland were studied. 1) Cofactors: Immunologic Status (IC3), 2) Disease Stages (IIIC), 3) Immunological Aspects (IIE), 4) Geographic Trends: Europe (Finland) (IB4), 5) Populations: Homomsexuals (IA 1) 1C3-Ran-9 Author(s): Title: Source: Institution: Findings: Method: Schechter, Martin T., MD, MSc, PhD; Boyko, William J., MD, FRCPC; Jeffries, Eric, MB, MPH, FRCPC; Willoughby, Brian, MD, CCFP; Nitz, Rod, MD; Constance, Peter, MB, BS; Weaver, Michael, PhD; Wiggs, Barry, MSc; O'Shaughnessy, Michael, PhD. The Vancouver Lymphadenopathy-AIDS Study: 4. Effects of Exposure Factors, Cofactors, and HTLV-III Seropositivity on Number of Helper T Cells. Canadian Medical Association Journal, 15 August 1985, Vol. 133: 286- 292. St. Paul's Hospital and the University of British Columbia, Vancouver, Canada (Schechter, Boyko, Jeffries, Willoughby, Nitz, Constance, Weaver, Wiggs); and the Division of Viral Studies, Laboratory Centre for Disease Control, Department of National Health and Welfare, Ottawa, Canada (O'Shaughnessy). This report investigated the contributions of various exposure factors (e.g., number of sexual partners, sexual practices) and potential cofactors (e.g., drug use, infectious disease, cigarette smoking) to immune dysfunction in a group of 219 homosexual men. At the time of analysis, 141 men (64%) were human T-cell lymphotropic virus type III (HTLV-II) seronegative and 78 (36%) were seropositive, a rate similar to the overall prevalence of seropositivity (34%) observed in the larger study population from which these 219 subjects were drawn. No sexual practice studied -- insertive or receptive anal intercourse, oral-genital contact, oral-anal contact, "fisting" (manual-anal contact), or large numbers of male sexual partners -- showed any effect on helper T-cell counts after HTLV-III antibody status was taken into account. A history of mononucleosis was associated with a lower mean helper T- cell count in both seronegative and seropositive men. A history of hepatitis in seronegative men correlated with a higher mean helper T- cell count; in seropositive men the correlation was with a lower mean helper T-cell count. No venereal disease (gonorrhea, syphilis, venereal warts, pubic lice, or genital herpes) had an effect on helper T cell count. Illicit drug use -- MDA (an amphetamine), LSD, cocaine, amphetamines, heroin -- did not change the helper T-cell count, but both seropositive and seronegative participants who smoked cigarettes showed higher mean numbers of helper T cells. The authors suggest that in the context of HTLV-II infection, viruses may act synergistically to potentiate the effects of HTLV-II, but that further monitoring is required to understand these effects more fully. The group of 219 men was selected because complete HTLV-III antibody and lymphocyte subset results were available for study. Participants completed a self-administered questionnaire and underwent complete physical exams (including measurement of lymph node size) and laboratory testing on two occasions at least 3 months apart. Testing for HTLV-II antibody was done by enzyme-linked immunosorbent assav 1C3-Sch-10 Sample Size: Policy Keys: (ELISA). ELISA values greater than 10 were considered positive. Sera with ELISA values between 3 and 10 were analyzed by the Western blot technique and reported as positive if antibodies were detected against proteins of molecular weight 41,000 or 24,000 or both. The study sample included 219 male homosexuals from a larger cohort of 726 homosexual men recruited from six general practices in central Vancouver, British Columbia, between November 1982 and February 1984. 1) Cofactors: Drug Exposure, Other Infections (IC3,2), 2) Immunological Aspects (IIE), 3) Transmission: Sexual Activity (IIA) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Carne, C.A.; Sutherland, S.; Ferns, R.B.; Mindel, A.; Weller, [.V.D.; Cheingsong-Popov, R.; Williams, P.; Tedder, R.; Adler, M.W. Rising Prevalence of Human T-Lymphotropic Virus Type III (HTLV-II) Infection in Homosexual Men in London. The Lancet, | June 1985, Vol. 1, No. 8440: 1261-1262. Academic Department of Genitourinary Medicine, Virology Section, Department of Microbiology, Middlesex Hospital Medical School and University College Hospital; Institute of Cancer Research, Chester Beatty Laboratories, London, England. This study describes changes in the prevalence of antibody to human T- cell lymphotropic virus type III (HTLV-II) among unselected British homosexual men attending a London sexually transmitted disease (STD) clinic and examines whether previous infection with hepatitis B virus (HBV) correlates with HTLV-II infection. The prevalence of antibody to HTLV-II was found to have increased from 3.7% (4 of 107) during one week in March 1982 to 21% (26 of 124) during one week in July 1984. Seropositive men had a significantly higher prevalence of infection with HBV than did seronegative men. Of the 33 seropositive men in 1984, 27 (82%) were symptomless or had only local genitourinary symptoms attributable to the STD for which they were attending the clinic. The evidence suggests, according to these authors, that HTLV-III was initially an imported but is now an endemic sexually transmitted agent in the United Kingdom. As of July 1984, at least 2,600 homosexual men in London would probably have been infected. Blood samples from all men who had been tested for syphilis (262 sam- ples) at an STD clinic in London from 22 to 26 March 1982 were frozen and stored. This procedure was repeated for another group of patients from 16 to 20 July 1984 (270 samples). Of the patients seen in 1984, five with persistent generalized lymphadenopathy and one with AIDS were attending an AIDS research clinic and were excluded. Patient notes for the two periods were analyzed retrospectively for age, sexual orientation, nationality, past STDs, and symptoms at presentation to the clinic. The blood samples were tested for antibodies to HTLV-III and the core protein of HBV by radioimmunoassay. One hundred and fifty-three homosexual and bisexual London men were studied in 1982, another 153 homosexual and bisexual London men were studied in 1984. These two groups showed no statistically significant differences in age, social class, nationality, or number of prior STDs. 1) Cofactors: Hepatitis B Virus (IC3), 2) Geographic Trends: Europe (U.K.) (IB4), 3) Populations: Homosexuals (IA1) 1C3-Car-11 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Tedder, R.S.; Shanson, D.C.; Jeffries, D.J.; Cheingsong-Popov, R.; Dalgleish, A.; Clapham, P.; Nagy, K.; Weiss, R.A. Low Prevalence in the UK of HTLV-I and HTLV-II Infection in Subjects with AIDS, with Extended Lymphadenopathy, and at Risk of AIDS. The Lancet, 21 July 1984, Vol. 2, No. 8395: 125-128. Virology Section, Department of Microbiology, Middlesex Hospital Medical School, London (Tedder); Department of Microbiology, St. Stephen's Hospital, London (Shanson); Division of Virology, Department of Medical Microbiology, St. Mary's Hospital Medical School, London (Jeffries); Chester Beatty Laboratories, Institute of Cancer Research, London, England (Cheingsong-Popov, Dalgleish, Clapham, Nagy, Weiss). Since human T-cell leukemia virus type [ (HTLV-I) has been shown to be transmissible by blood transfusion and has been reported in American homosexual AIDS patients, this serological survey was undertaken to determine whether HTLV-I is associated with persisting lymphadenopathy, but not necessarily a cause of AIDS. Antibodies to HTLV-I were detected in 5% of patients with lymphadenopathy syndrome and in less than 1% of unselected homosexual patients and drug abusers. None of 22 AIDS patients, 85 hemophiliacs, or 940 blood donors were positive for HTLV-I antibodies. Three of 13 drug addicts were positive for HTLV-II. Although infection by HTLV-I and HTLV-II occurs more frequently in patients with lymphadenopathy and drug addicts than in the U.K. population as a whole, the low prevalence of these infections in patients with lymphadenopathy or AIDS indicates that these two strains of HTLV are not the cause of AIDS. In a London case-control study in 1982, blood samples were collected from 800 homosexual and 26 promiscuous heterosexual men attending genitourinary clinics in London. Eighty-five samples from hemophiliacs and 113 from drug addicts were also tested. A large group of blood donors was used as a control. Blood was tested for antibodies to HTLV-I and HTLV-II. Eight hundred homosexual and 26 promiscuous heterosexual men were cases; 500 unselected blood donors and 440 selected blood donors born outside northwest Europe were examined. Also, 85 samples from hemophiliacs and 113 from drug addicts were tested. 1) Cofactors: HTLV-I and HTLV-II (IC3), 2) Geographic Trends: Europe (United Kingdom) (IB4) 1C3-Ted-12 Author(s): Title: Source: [nstitution: Findings: Method: Quinnan, Gerald V., Jr., MD; Masur, Henry, MD; Rook, Alain H., MD; Armstrong, Gary; Frederick, Winston, R., MD; Epstein, Jay, MD; Manischewitz, Jody F., MS; Macher, Abe M., MD; Jackson, Lozannie; Ames, John; Smith, Holly A.; Parker, Margaret, MD; Pearson, Gary R., PhD; Parrillo, Joseph, MD; Mitchell, Charles, MD; Straus, Stephen E., MD. Herpesvirus Infections in the Acquired Immune Deficiency Syndrome. Journal of the American Medical Association, 6 July 1984, Vol. 252, No. 1: 72-77. Division of Virology, Office of Biologics Research and Review, Center for Drugs and Biologics, Food and Drug Administration (Quinnan, Rook, Frederick, Epstein, Mitchell, Armstrong, Manischewitz, Jackson); Critical Care Medicine Department and Clinical Pathology Department, Clinical Center, National Institutes of Health (Masur, Parker, Parrillo, Ames); Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health (Straus, Smith), Bethesda, Maryland; Mayo Clinic, Rochester, Minnesota (Pearson). This study investigated the prevalence and clinical significance of herpesvirus infection in patients with and at risk for AIDS. Herpesviruses are well-known causes of serious disease in patients with compromised cellular immunity (for example, bone marrow transplant patients). Frequently occurring infectious agents in these patients include all herpesviruses, including herpes simplex virus (HSV), Epstein- Barr virus (EBV), and cytomegalovirus (CMV). Many AIDS manifestations are similar to those of CMV or EBV infections: a mononucleosislike syndrome (fever, malaise, weight loss) and lymphadenopathy. Of the five groups tested, herpesvirus infection was common in all groups, but CMV and EBV infections were more common than HSV and varicella-zoster virus (VZV) infections. Of 34 AIDS patients, 34 had CMV, 33 had EBV, 8 had HSV, and 4 had VZV. Thirteen AIDS patients died during the study; CMV infections seemed to be related in the deaths of 12 of these 13. Of 9 lymphadenopathy patients, 8 had CMV and all had EBV. Of 13 asymptomatic homosexual men, 5 had active CMV infec- tions; of 8 healthy homosexual men tested, 7 had active EBV infections. The prevalence of herpesvirus infections in AIDS and the frequent serious diseases associated with these, and the prevalence of CMV and EBV in AIDS and lymphadenopathy, may indicate an important interaction between these viruses and the cause of AIDS. All patients were followed up clinically for a minimum of four months or until death. All patients with AIDS were studied for lymphocyte subset abnormalities, isolation of HSV, CMV, and VZV was attempted in culture. Tissue biopsy specimens were cultured for CMV, and lymph node biopsy specimens were cultured for CMV and EBV. Antibody titers against CMV and EBV were measured at initial examination of all patients. Specimens were obtained for repeated tests at four- to eight-week intervals from 14 patients with AIDS and 6 patients with lymphadenopathy. 1C3-Qui-13 Sample Size: Policy Keys: Subjects included 34 AIDS patients, 9 patients with chronic generalized lymphadenopathy, and 13 asymptomatic homosexual males. Twenty- seven of the AIDS patients were male homosexuals, | was a hemophiliac, 1 was a recent Haitian immigrant, 3 had received blood transfusions, and 2 denied belonging to any risk group. Three subjects were female. All of the lymphadenopathy syndrome patients were homosexually active males. All the male homosexual subjects had more than 30 lifetime partners and some recreational drug use. 1) Cofactors: Other Infections (IC3) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Detels, Roger, MD, MS; Visscher, Barbara R., MD, DPH; Fahey, John L., MD; Schwartz, Kendra, MPH; Greene, Richard S., MPH; Madden, David L., DVM, PhD; Sever, John L., MD, PhD; Gottlieb, Michael S., MD. The Relation of Cytomegalovirus and Epstein-Barr Virus Antibodies to T- Cell Subsets in Homosexually Active Men. Journal of the American Medical Association, 6 April 1984, Vol. 251, No. 13: 1719-1722. School of Public Health (Detels, Visscher, Greene, Schwartz); School of Medicine (Fahey, Gottlieb), University of California, Los Angeles; National Institutes of Health, Bethesda, Maryland (Madden, Sever). This study examined the relationships among sexual practices and immune status, measured by distributions of T-cell subsets and levels of antibodies to cytomegalovirus (CMV) and Epstein-Barr virus (EBV), in homosexual men. Of 89 homosexually active study participants, 96% showed antibody to CMV and 94% showed antibody to EBV. The titer of CMV antibody was higher among those practicing receptive anal intercourse, and the amount of CMV antibody was positively correlated with low helper/suppressor T-cell ratio, number of lifetime sexual partners, number of venereal disease episodes, number of T-suppressor cells, and level of EBV antibody. Of the study participants, 12% had a low helper/suppressor T-cell ratio only, 18% showed suppressor T-cell augmentation, and 3% showed helper T-cell deficiency. The level of CMV antibody and the prevalence of receptive anal intercourse were higher in these three groups. However, prevalence of antibody to both CMV and EBV in study subjects not practicing receptive anal intercourse was within the normal range reported for non-homosexually active men. This suggests that CMV infection is acquired through receptive anal intercourse and that it is associated with an increase in suppressor T- cells and, in some cases, a decrease in helper T-cells. Subjects were recruited through a homosexual association at UCLA and asked to complete a self-administered questionnaire about demographic factors, venereal disease history, history of other illness, and specific sexual practices. Blood samples were drawn, separated, and preserved by freezing. Levels of antibody to CMV were determined by enzyme-linked immunosorbent assay. Levels of antibody to EBV were determined by indirect fluorescent antibody technique. Study subjects were 89 homosexual men in Los Angeles, some of whom had generalized symptoms of prodromal AIDS, including lymphadeno- pathy. Their mean age was 27 years, mean number of lifetime sexual partners was 264, and mean total reported episodes of venereal disease was 5.8. 1) Cofactors: Other Infections (CMV, EBV) (IC3), 2) Transmission: Sexual Activity (IIA), 3) Immunological Aspects (IIE), 4) Populations: Homosexuals (IA) 1C3-Det-14 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Services, U.S. Department of Health and Human Services. Human T-Cell Leukemia Virus Infection in Patients with Acquired Immune Deficiency Syndrome: Preliminary Observations. Morbidity and Mortality Weekly Report, 13 May 1983, Vol. 32, No. 18: 233-234. Centers for Disease Control, Atlanta, Georgia. Recent evidence suggests that human T-cell leukemia virus (HTLV) infection occurs in patients with AIDS. HTLV has been isolated from peripheral blood T lymphocytes from several AIDS patients, and a retrovirus related to but clearly distinct from HTLV has been isolated from a lymph node of a patient with lymphadenopathy syndrome (LAS). HTLV has been detected in 2 of 33 (6%) AIDS patients, and antibodies have been found in 19 of 75 (25%) AIDS patients. Such antibodies were rarely found in blood sera collected from homosexual men in New York in 1978 or from blood donors in a mid-Atlantic state who gave blood in 1977. This report reviews several studies attempting to isolate HTLV or antibodies to HTLV from AIDS patients. The study samples included: 33 AIDS patients not described; 75 AIDS patients, 34 with Kaposi's sarcoma alone, 30 with Pneumocystis carinii pneumonia alone, and ll with both diseases; 23 LAS patients not described; 81 New York City homosexual men in 1981; 118 Chicago homosexual men visiting a venereal disease clinic in 1978; and 137 mid- Atlantic blood donors unselected for sexual preference in 1977. 1) Cofactors: HTLV Causes AIDS (IC3) 1C3-Cen-15 [I. Transmission Modes A. Sexual Activity Author(s): Title: Source: Institution: Findings: Method: Sample Size: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Positive HTLV-III/LAV Antibody Results for Sexually Active Female Members of Social/Sexual Clubs--Minnesota. Morbidity and Mortality Weekly Report, 14 November 1986, Vol. 35, No. 45: 697-699. Centers for Disease Control, Atlanta, Georgia. Serologic screening for human T-cell lymphotropic virus type [II/lymphadenopathy-associated virus (HTLV-III/LAV) antibodies was conducted among the members of two social/sexual clubs in Minnesota because the members were known to have been involved in outbreaks of other sexually transmitted diseases. Of 134 volunteers tested in June and July 1986 (75 men and 59 women), 2 women had positive antibody test results for HTLV-III/LAV by both enzyme-linked immunosorbent assay (ELISA) and Western blot. Their antibody results were again positive when the tests were repeated 6 weeks later. The seroprevalence rate of 3% among female club members tested is significantly higher than the rate of zero among 56,000 female blood donors in Minnesota. One woman was married and had sexual relations only with other club members; her husband (also a member) had negative antibody test results. The other woman was unmarried and occasionally had sexual relations with men outside the club. Both women reported having sexual contact with more than 25 other members. Two of five men with whom they had both had contact were negative for HTLV-III/LAV antibody. Two of the other three men were reported to be bisexual and had had repeated vaginal and anal intercourse with both women, but their serologic status could not be determined. An additional bisexual man who was a former member of one of these clubs has developed AIDS, but he had not had sexual contact with either of the seropositive women or the bisexual men mentioned above. To date, 55 of the 134 members tested have participated in follow-up interviews and have received counseling about their sexual practices and attitudes. When asked whether they perceived themselves as being at risk of contracting AIDS, 40 members (73%) replied no. One man reported that he "usually" used condoms. When asked whether they would continue to participate in the activities promoted by social/sexual clubs if they knew that such activities were considered very risky, 98% answered that they would not. When it was known that one member of each club was seropositive, both clubs disbanded. Club members were tested for antibody to HTLV-III/LAV by ELISA. Positive specimens were also tested by Western blot and retested by ELISA and Western blot 6 weeks later. Volunteers for follow-up interviews have been counseled about their sexual practices and attitudes. Of 285 members (143 women and 142 men) of two social/sexual clubs in the Minneapolis-St. Paul area, 134 volunteers (75 men and 59 women) 2A-Cen-—1 Policy Keys: were tested for HTLV-III/LAV antibodies in June and July 1986. The two seropositive women had belonged to two different social/sexual clubs for approximately 2 years. Both denied intravenous drug use, a history of blood transfusions, or receipt of clotting-factor concentrates. One woman was 31 years old and married, and the other was 25 years old and unmarried. 1) Transmission: Sexual Activity (IIA), 2) Information/Education: Public Awareness, Risk Behaviors and Protection (VAl,2), 3) Populations: Heterosexuals (IA6) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Burger, Harold, PhD, MD; Weiser, Barbara, MD; Robinson, William S., MD; Lifson, Jeffrey, MD; Engleman, Edgar, MD; Rouzioux, Christine, PhD; Brun-Vezinet, Francoise, MD; Barre-Sinoussi, Francoise, PhD; Montagnier, Luc, MD; Chermann, Jean-Claude, PhD. Transmission of Lymphadenopathy-Associated ~~ Virus/Human T Lymphotropic Virus Type III in Sexual Partners: Seropositivity Does Not Predict Infectivity in All Cases. The American Journal of Medicine, July 1986, Vol. 81: 5-10. Divisions of Infectious Diseases and Immunology, Department of Medicine, Stanford University School of Medicine, Stanford, California; Laboratoire Central, Virologie, Hopital Claude Bernard, and Departement de Virologie, Unite Oncologie Viral, Institut Pasteur, Paris, France. This study examined the transmission of lymphadenopathy-associated virus (LAV) between long-term sexual partners and the relationship between seropositivity and sexual transmission in nine couples (hetero- sexual and homosexual) at increased risk for AIDS. No consistent pattern of LAV seropositivity or depression of immunity emerged. For two of five heterosexual couples, transmission of LAV occurred from a seropositive man at increased risk to his monogamous wife; in one couple, the wife of a man with hemophilia had LAV antibody and evi- dence of reduced immunity; in the other couple, the wife of a bisexual intravenous drug user had AIDS. Neither woman had a recognized AIDS risk factor except marriage to a seropositive man at increased risk. No clear pattern of LAV seropositivity or T lymphocyte abnormalities were observed in these couples in relation to their sexual histories. Study of the other couples revealed that regular sexual contact with seropositive persons over long periods did not lead to evidence of LAV infection. These findings suggest that the presence of LAV antibody does not always indicate a high degree of infection (or that susceptibility to infection may vary). Subjects were interviewed for sexual and medical history. Virological and immunological testing was performed. Nine Caucasian American couples (five heterosexual and four homo- sexual) at increased risk for AIDS were studied. All 18 subjects were recruited by physician referrals in the San Francisco Bay area. All couples had maintained steady sexual relationships for more than | year. 1) Transmission: Sexual Activity (IIA), 2) Cofactors: Seropositivity and Infectivity (IC4), 3) Populations: Heterosexuals (IA6) 2A-Bur-2 Author(s): Title: Source: Institution: Findings: Method: Sample Sise: Jason, Janine M., MD; McDougal, J. Steven, MD; Dixon, Gloria, RN; Lawrence, Dale N., MD; Kennedy, M. Susan, MT; Hilgartner, Margaret, MD; Aledort, Louis, MD; Evatt, Bruce L., MD. HTLV-II/LAV Antibody and Immune Status of Household Contacts and Sexual Partners of Persons with Hemophilia. Journal of the American Medical Association, 10 January 1986, Vol. 255, No. 2: 212-215. Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Jason, McDougal, Lawrence, Evatt, Dixon, Kennedy); the Hemophilia Center, New York Hospital--Cornell Medical Center (Hilgartner); Mount Sinai School of Medicine (Aledort), New York. This study evaluates the prevalence of antibody to human T-cell lymphotropic virus type III (HTLV-II) and assessed the HTLV-III immune status of 43 hemophiliacs and 88 of their household members and sexual partners. Twelve of the hemophiliacs had AIDS, and five had AIDS- related complex (ARC). Seventeen other hemophiliacs were clinically well but found to be HTLV-III positive, and nine were well and HTLV-III negative. No nonhemophiliac household contacts of healthy hemophiliacs were HTLV-II positive; 2 of 33 nonhemophiliac contacts of hemophiliacs with AIDS or ARC who did not report risk factors were positive for HTLV-III antibodies. One of these was a spouse and one was a sexual partner of a hemophiliac. One of these antibody-positive contacts herself had AIDS, and one had ARC. Antibody-negative nonhemophiliac contacts of hemophiliacs with AIDS or ARC and of antibody-positive hemophiliacs had lower numbers of T-cells than did contacts of antibody-negative hemophiliacs. The authors conclude that risk of HTLV-II transmission may exist for spouses and sexual contacts of hemophiliacs with AIDS or ARC, but the risk for contacts of asymptomatic hemophiliacs is uncertain. This was an epidemiological and immune status study of hemophiliacs and their household contacts and sexual partners. Blood serum specimens of the volunteer subjects were tested for HTLV-III/LAV antibody by Western blot analysis. T-cell subpopulations were quantitated by indirect immunofluorescence, with OKT3, OKT4, and OKT& antibodies. A total of 131 subjects, including 88 household contacts and sexual partners of 43 hemophiliacs, were studied. The subjects in the house- holds with asymptomatic hemophiliacs consisted of the following: participants from nine New York City area households included seven sexual partners, two parents, and nine hemophiliacs; participants from 16 Georgia households consisted of one sexual partner, 17 siblings (4 with hemophilia A themselves), 24 parents, one grandparent, and 16 hemophiliacs; an Ohio household included a hemophiliac participant, one parent, and one sibling. The households with hemophiliacs with ARC consisted of five symptomatic hemophiliacs, five sexual partners, one 2A-Jas-3 Policy Keys: son, and two parents. The group of households with hemophiliacs with AIDS consisted of 12 AIDS-afflicted hemophiliacs, nine sexual partners, four siblings, four parents, and nine children. 1) Transmission: Sexual Activity (IIA), 2) Populations: Hemophiliacs (IA3), 3) Transmission: Casual Contact (IIF), 4) Geographic Trends: U.S. (IB1) Author(s): Title: Source: Institution: Findings: Methods: Sample: Goedert, James J.; Biggar, Robert J.; Winn, Deborah M.; Mann, Dean L.; Byar, David P.; Strong, Douglas M.; DiGloia, Richard A.; Grossman, Ronald J.; Sanchez, William C.; Kase, Ronald G.; Greene, Mark H.; Hoover, Robert N.; Blattner, William A. Decreased Helper T Lymphocytes in Homosexual Men: II. Sexual Practices. American Journal of Epidemiology, 1985, Vol. 121, No. 5: 637-644. Environmental Epidemiology Branch (Goedert, Biggar, Winn, Kase, Greene, Hoover, Blattner), Laboratory of Human Carcinogenesis (Mann), and Biometry Branch (Byar), Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland (Strong). This study of the sexual practices of 245 homosexual male outpatients found that an increasing number of homosexual partners was correlated, in the entire study group combined, with decreasing helper T-cell counts and reduced helper/suppressor T-cell ratios. Three risk groups were defined a priori: high-risk men from central Manhattan, intermediate- risk men from Washington, DC, with AIDS-area homosexual contacts, and low-risk Washington, DC, men without such contacts. Suppressor T-cell counts were unrelated to the number of partners in all three groups. Increasingly frequent receptive anal intercourse correlated with decreasing helper T-cell counts most clearly in the New York City group, somewhat less so in the intermediate-risk Washington exposed group, and not at all in the Washington unexposed group. This association persisted after adjusting for other sexual practices, the number of sexual partners, and other confounding variables. The authors conclude that a transmissible agent associated with receptive anal intercourse best explains these results, and that the cause of these low helper T-cell counts may also be the cause of AIDS. Comparisons were made of homosexual men having sexual contacts with persons from high-risk areas (San Francisco, New York, and Los Angeles) with homosexual men without such contacts. Patients who agreed to participate completed a self-administered questionnaire about medical conditions, drug use, and sexual practices. All subjects were given physi- cal exams by one of two physicians, including drawing blood samples for white blood cell count and for OKT4 and OKT& monoclonal antibody tests as measures of helper and suppressor T-cell counts. Descriptive and multivariate statistical analyses were performed. A total of 245 homosexual men were recruited from the patient populations from May to June 1982 of a private physician in New York City (85 patients), and two private physicians in Washington, D.C. (160 patients). The New York City group had an average age of 36 years, was 91% white, averaged 78 homosexual partners in the previous year, and averaged 59 days of nitrite inhalant use in the previous year. Among the Washington group, 96 men (60%) reported at least one sexual contact between January 1980 and June 1982 with men in one of three high-risk 2A-Goe-4 Policy Keys: cities (New York, San Francisco, and Los Angeles). This "exposed" group of D.C. men had a mean age of 33 years, was 80% white, averaged 42 homosexual partners in the previous year, and averaged 42 days of nitrite inhalant use in the previous year. The Washington "unexposed" group of 64 men (40%) had a median age of 34 years, was 78% white, averaged 26 homosexual partners in the previous vear, and averaged 24 days of nitrite inhalant use in the previous year. I) Transmission: Sexual Activity (IIA), 2) Cofactors: Demographic Status (ICl), 3) Geographic Trends: U.S. (IBl), 4) Populations: Homosexuals (IA 1), 5) Immunologic Aspects (IIE) Author(s): Title: Source: Institution: Findings: Method: Gazzard, B.G.; Farthing, C.; Shanson, D.C.; Lawrence, A.G.; Tedder, R.S.; Cheingsong-Popov, R.; Dalgleish, A.; Weiss, R.A. Clinical Findings and Serological Evidence of HTLV-II Infection in Homosexual Contacts of Patients with AIDS and Persistent Generalised Lymphadenopathy in London. The Lancet, | September 1984, Vol. 2, No. 8401: 480-483. Departments of Medicine, Clinical Microbiology, Dermatology, and Genitourinary Medicine, St. Stephen's Hospital, London (Gazzard, Farthing, Shanson, Lawrence); Virology Section, Department of Microbiology, Middlesex Hospital Medical School, London (Tedder); Chester Beatty Laboratories, Institute of Cancer Research, London, England (Cheingsong-Popov, Dalgleish, Weiss). Between 1980 and 1984, 28 Caucasian men resident in central London who had had anogenital intercourse with patients who had either AIDS or persistent generalized lymphadenopathy were followed up to observe the clinical spectrum of disease in men who had had sexual contact with subjects with AIDS or lymphadenopathy and to correlate development of symptoms with HTLV-II seropositivity. The pattern of sexual links indicated that within this group there were two clusters, one of 7 men and one of 13 men. Seventeen of the total 28 contacts became ill with either AIDS or lymphadenopathy; among those in the clusters, 4 died of AIDS, 11 had lymphadenopathy, and of the rest, 2 had no lymphadeno- pathy. Sixteen of the 19 men in the clusters who were tested for human T-cell lymphotropic virus type III (HTLV-II) antibody were positive, as were 7 of those not in the clusters. None of the four who died of AIDS had had contact with each other. Two in the first cluster seemed to have been linked by a symptomless HTLV-III-negative sexual contact, who was also probably the link between the two clusters. In the second cluster the chief "carrier" seemed to be a seropositive man who later developed lymphadenopathy. Controls for antibody status were lll men attending a genitourinary medicine clinic who had no known contact with either AIDS or lymph- adenopathy patients and who were being screened for syphilis. Of these, 19 of 86 who were homosexual and 0 of 25 who were heterosexual were positive for HTLV-III antibodies. Only | of the 19 seropositive controls became ill with lymph node disease; the other 18 remained well. These findings are consistent with the hypothesis that HTLV-II is the sexually transmitted causative agent of AIDS and lymphadenopathy. This contact-tracing study consisted of cluster analysis and prospective study of homosexual men who had had anogenital intercourse with men suffering from AIDS or lymphadenopathy, with a 4-year (1980-84) follow- up, as well as a case-control study of antibodies to HTLV-II and subsequent illness. Serological tests and clinical examinations were performed. 2A-Gaz-5 Sample Size: Policy Keys: Twenty-eight white homosexual contacts of patients with AIDS or chronic lymph node disease in London were studied. Controls for antibody status were lll patients attending a genitourinary clinic in 1984, undergoing testing for syphilis. 1) Transmission: Sexual Activity (IIA), 2) Populations: Homosexuals (IA1), 3) Geographic Trends: Europe (U.K.) (IB4) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Auerbach, David M., MD; Darrow, Willaim W., PhD; Jaffe, Harold W., MD; Curran, James W., MD, MPH. Cluster of Cases of the Acquired Immune Deficiency Syndrome: Patients Linked by Sexual Contact. The American Journal of Medicine, March 1984, Vol. 76: 487-492. Field Services Division, Epidemiology Program Office, and AIDS Activity, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. This study investigates the possibility that homosexual patients with AIDS had been sexual partners of each other. Nine of 13 male homosexual AIDS patients in California were found to have had sexual contact with one or more AIDS patients within 5 years prior to onset of symptoms. The study linked 40 patients in 10 U.S. cities by sexual contact with AIDS patients. On the basis of six pairs of patients, a mean latency period of 10.5 months (range, 7 to l4 months) was estimated between sexual contact and onset of symptoms. The implication of this clustering is that AIDS Is caused by an infectious, sexually transmitted agent. The 40 patients linked by sexual contact were significantly more likely to be white and to have only Kaposi's sarcoma than a comparison group of 208 nonlinked AIDS patients, but differences between the two groups In dimensions of intravenous drug use, homosexual exclusivity, Manhattan residence, deceased status when reported, and age 35 years or older were not significant. Interviews with a subset of linked and nonlinked patients demonstrated that linked patients were more likely than nonlinked patients to have met sexual partners in bathhouses, to have frequently used inhaled amyl or butyl nitrite, and to have participated in manual-rectal intercourse ("fisting"). Use of other recreational drugs and participation in other sexual activities were not significantly different for the two groups. Patients in both groups tended to have large numbers of sexual partners. These observations suggest that AIDS is caused by an infectious agent and that sexual partners of AIDS patients appear to be at increased risk for AIDS. Sexual-contact histories were obtained for 19 previously healthy homosexual males in Southern California with biopsy-confirmed Kaposi's sarcoma or Pneumocystis carinii pneumonia. Interviews were conducted with the 8 living patients and close companions of the ll deceased patients to obtain names of sexual partners during the 5 years prior to illness. For a link to be noted, the named sexual partner (or his surviving close companion) had to confirm (or not deny) the contact. Forty linked patients were compared with 208 nonlinked patients, those who were not known to have been sexual partners of other AIDS patients. Twenty-nine linked patients and 49 nonlinked patients were interviewed on certain soclal and sexual behavior patterns. The study sample consisted of 19 previously healthy Southern California homosexual men with biopsy-confirmed Kaposi's sarcoma or P. carinii pneumonia; 8 were living and 11 were deceased. These patients were linked by sexual contact to 40 patients in 10 U.S. cities. Comparison 2A-Aue-6 Policy Keys: data are also presented for 208 other homosexual male patients with AIDS who were reported to the Centers for Disease Control as of [2 April 1982, but not named as sexual partners of patients included in the cluster. 1) Transmission: High-Risk Sexual Behavior (IIA), 2) Incubation Period (IIIC), 3) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA1), 4) Populations: Homosexuals (IA). Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Detels, Roger; Schwartz, Kendra; Visscher, Barbara R.; Fahey, John L.; Greene, Richard S.; Gottlieb, Michael S. Relation Between Sexual Practices and T-Cell Subsets in Homosexually Active Men. The Lancet, 19 March 1983, Vol. I, No. 8325: 609-611. School of Public Health and School of Medicine, University of California, Los Angeles, California. This early study investigated the immunological status of young, healthy, homosexually active men in Los Angeles. Whereas previous studies had found that a decrease in both suppressor and helper T cells was a characteristic of AIDS, this study found a low (less than or equal to 0.8) helper /suppressor T-cell ratio in 27% (24 of 89) of the study group due to a significantly raised mean number of suppressor T cells. Passive (receptive) anal intercourse was found to be associated with this condition, which the authors call acquired immune augmentation, in healthy, actively homosexual males; those practicing receptive anal intercourse had a significantly higher mean number of suppressor cells than did those practicing only active (insertive) anal intercourse or no anal intercourse. Whether acquired immune augmentation is a precursor of AIDS or an unrelated disorder needs to be determined. (Current belief is that patients with this disorder were infected with human immunodefi- ciency virus.) Subjects completed a self-administered interview schedule that asked for demographic information, venereal disease history, general illness information, age at first intercourse, estimated number of lifetime sexual partners, and specific sexual practices engaged in. Blood samples were drawn, separated, and tested for immunofluorescence in the presence of Leu-2 and Leu-3 commercial antibodies. A group of 89 healthy, homosexually active Los Angeles men was recruited from a gay and lesbian association at the University of California, Los Angeles; their ages ranged from 20 to 44 years (mean, 27). Study subjects reported a mean number of lifetime sexual partners of 264 and a mean number of venereal disease episodes of 5.8. Ten subjects reported chronic lymphadenopathy. 1) Transmission: Sexual Activity (IIA), 2) Immunological Aspects (IIE), 3) Populations: Homosexuals (IA 1), 4) Precursors of AIDS (IIIB) 2A-Det-7 [I. Transmission Modes B. LV. Drug Abuse (shared needles) Author(s): Title: Source: Institution: Findings: Method: Robertson, J.R.; Bucknall, A.B.V.; Welsby, P.D.; Roberts, J.J.K.; Inglis, J.M.; Peutherer. J.F.; Brettle, R.P. Epidemic of AIDS Related Virus (HTLV-III/LAV) Infection Among Intravenous Drug Abusers. British Medical Journal, 22 February 1986, Vol. 292, No. 6519: 527-529. Edinburgh Drug Addition Study, West Granton Medical Group, Edinburgh (Robertson, Roberts, Bucknall); City Hospital, Edinburgh (Welsby, Brettle, Inglis); Bacteriology Department, University of Edinburgh, Edinburgh, Scotland (Peutherer). During late 1983 and early 1984, human T-cell lymphotropic virus type [lI/lymphadenopathy-associated virus (HTLV-III/LAV) infection became epidemic in an economically poor section of Edinburgh and then became endemic to the area. This clinical study tested 164 current and former intravenous (I.V.) heroin users in this section of Edinburgh for HTLV- I[II/LAV infection. Of these, 83 (51%) were seropositive for antibodies to HTLV-III/LAV (60 men, 23 women; mean age, 24.1 years), well above the prevalence reported elsewhere in Britain and Europe and close to that reported in New York City. Because of the lapse of time between the latest sample tested and the present, and because of continued drug use, prevalence may now be as high as 85% in this population. There were 81 (49%) seronegative patients (55 men, 26 women; mean age, 26.9 years). Although complete data are unavailable, the authors hypothesize that 57 patients may have seroconverted after serum samples were tested. At the time of the study, no patient had AIDS, although a growing number showed signs of AIDS-related illnesses. The mean duration of heroin use was 4.6 years for seropositive patients and 6.1 years for seronegative patients, indicating seropositivity was not related to duration of drug use. However, a correlation was found between the frequency of sharing equipment and seropositivity. Although it is not clear how the virus was introduced into this population (this cohort reported very little use of heroin outside Edinburgh), the rapid spread of infection appears to have resulted from a combination of exclusive intravenous use of heroin (98%), the frequency of sharing equipent (83%), and specifics of injection practices. In particular, equipment, which belonged to the supplier and was used by different groups of people each day, was at best rinsed with tap water between injections. No serious attempt at sterilization was made despite the routine practice of "washout": drawing blood back into the syringe after injection to flush out any remaining heroin. These practices appear to have continued throughout 1984 and have been moderated only recently owing to anxiety about the risk of AIDS. This clinical study tested stored blood samples for antibody to HTLV- I[II[/LAV by enzyme-linked immunosorbent assay; positive results were confirmed by immunofluorescence or Western blot analysis or both. If the most recent serum was positive, previous samples (when available) were tested until negative results were obtained to identify the period of 2B-Rob-1 Sample Size: Policy Keys: seroconversion. Case summaries of patients' drug practices, lifestyle, and behavior were obtained from case notes and interviews. Stored blood samples (obtained between March 1981 and March 1984) for 164 current or former L.V. heroin users regularly attending an Edinburgh, Scotland, general practice (usually on a weekly basis) were examined. The subjects included long-term users, casual users, and nonaddicts who had experimented with heroin. 1) Transmission: LV. Drug Use (IIB), 2) Populations: [.V. Drug Users (IA2), 3) Geographic Trends: Europe (Scotland) (IB4) [I. Transmission Modes C. Blood Transfusion and Blood Products Author(s): Title: Source: Institution: Findings: Method: Anderson, Kenneth C., MD; Gorgone, Barbara C., MT(ASCP)SBB; Marlink, Richard G., MD; Ferriani, Roberta, BA; Essex, Myron E., DVM, PhD; Benz, Patricia M., BA; Groopman, Jerome E., MD. Transfusion-Acquired Human Immunodeficiency Virus Infection Among Immunocompromised Persons. Annals of Internal Medicine, October 1986, Vol. 105, No. 4: 519-527. Blood Component Laboratory, Divisions of Medicine and Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Cancer Biology, Harvard University School of Public Health, Boston, Massachusetts; Division of Hematology/Oncology, Department of Medicine, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts. This article documents nearly uniform transmission of human immunodeficiency virus (HIV) via blood products from a single donor to several immunocompromised patients with cancer. Serum samples from the asymptomatic index donor and from 9 of 10 living recipients of his blood products and preserved sera from two deceased recipients became positive for HIV antibody at a median of about | year after transfusion. High neutralizing activity levels of HIV antibody were noted in the asymptomatic donor, and moderate levels were observed in seropositive recipients who had not yet manifested symptoms or signs of HIV infec- tion. In contrast, absence of neutralizing activity was shown in the recipients with apparent symptoms. Serum samples drawn before the implicated transfusion from five of the nine seropositive recipients confirm that they were seronegative at that time, suggesting that seroconversion occurred after the transfusion. Only one recipient is alive and seronegative 2 years after transfusion. She was among the earliest patients transfused, and it is therefore possible that the donor was not yet infected with HIV. The spouse of one patient was found to be asymptomatic but HIV seropositive, while spouses and family members of nine other recipients remain seronegative and healthy. The seropositive index donor was the only donor who had provided blood components for all 11 recipients. Of the 66 other donors who provided blood components to more than one recipient, 53 have been shown to be seronegative, and the remaining 13 have not been tested. These data strongly support the view that this cluster of HIV infections is related to the one index seropositive donor. The authors conclude that HIV transmitted by transfusion appears to have an extremely high attack rate, even when the seropositive donor who is not immunocompromised remains healthy. A seropositive donor was identified, prompting investigation of all his previous donations and the recipients of those donations. Clinical histories of all recipients before and after receipt of this donor's blood products were reviewed. Living recipients and their sexual contacts and family members, as well as sexual contacts of deceased recipients, were 2C-And-1 Sample Size: Policy Keys: traced and medically counseled. They were tested for antibodies to HIV. The interval from transfusion to seropositivity or death was calculated. Their immunologic and clinical status was also assessed. The index seropositive donor had donated blood 14 times during the 17 months before the start of serologic screening for HIV in March 1985. The 25 (13 male, 12 female) multiply-transfused patients with cancer who received blood components from the index donor were studied. Ten were alive at the start of the study and 15 had died. Dates of transfusions ranged from November 1983 to February 1985. Six spouses, the parents and an identical twin of one pediatric patient, and the parents of three other recipients were also included in the study. 1) Transmission: Blood Products (IIC), 2) Incubation Period and Disease Stages (IIIC), 3) Transmission: Sexual Activity (IIA), 4) Cofactors: Immunocompromised Host (IC3) Author(s): Titles Source: Institution: Findings: Method: Sample Size: Policy Keys: Wood, Chester C., MD; Williams, Alan E., PhD; McNamara, James G., MD; Annunziata, Josephine A., BS; Feorino, Paul M., PhD; Conway, Christopher O., MS. Antibody against the Human Immunodeficiency Virus in Commercial Intravenous Gammaglobulin Preparations. Annals of Internal Medicine, October 1986, Vol. 105, No. 4: 536-538. Section of Clinical Immunology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut; The American Red Cross Biomedical Research and Development Laboratories, Bethesda, Maryland; Centers for Disease Control, Atlanta, Georgia. Intravenous gamma globulin made from donated blood products is the main treatment for patients with humoral immunologic defects. In this study, commercial preparations of intravenous gamma globulin available in the U.S. were tested for the presence of antibody against human immunodeficiency virus (HIV) and for evidence of viral infectivity. Similarly, the sera of immunodeficient patients before and after infusion were screened for antibodies against HIV. Eleven of 18 lots of gamma globulin were positive for antibody to HIV by Western blot analysis, but none of 17 preparation samples showed signs of viral activity (reverse transcriptase activity or virus antigen expression). All preinfusion serum samples from the patients were seronegative by Western blot, while 8 of 15 samples were seropositive after infusion. Seropositive patients returned to a seronegative state within 28 days after infusion. The authors conclude that although gamma globulin products contain antibody to HIV, the antibody appears to be transient and passive and is not associated with infection. In more than 3 years of intravenous gamma globulin preparation use, no immunologic, serologic, or epidemiologic evidence of transmission of AIDS by these preparations has been documented. The authors suggest that current methods of preparation either exclude or inactivate the virus. Eighteen lots of intravenous gamma globulin were tested for antibody to HIV by enzyme-linked immunosorbent assay (ELISA) and Western blot techniques. Assays for viral activity were also performed. Serum samples from patients were obtained immediately before and 30 minutes after an infusion. These paired samples were also tested for HIV by ELISA and Western blot. Twenty patients with immunologic defects receiving intravenous gamma globulin were studied. None of the patients had any clinical evidence of AIDS. Most of them had been receiving monthly intravenous gamma gobulin therapy for more than 2 years. 1) Transmission: Blood Products (IIC), 2) Blood Product Safety: Inactivation of Virus (VB3) 2C-Woo-2 Author(s): Titles Source: [nstitutions Findings: Method: Sample Size: Policy Keys: Goldman, Michel; Liesnard, Corinne; Vanherweghem, Jean-Louis; Dolle, Nicole; Toussaint, Charles; Sprecher, Suzy; Cogniaux, Jacqueline; Thiry, Lise. Markers of HTLV-III in Patients with End Stage Renal Failure Treated by Haemodialysis. British Medical Journal, 19 July 1986, Vol. 293: 161-162. Cliniques Universitaires de Bruxelles, Hopital Erasme, Universite Libre de Bruxelles (Goldman, Liesnard, Vanherwegham, Dolle, Toussant); Institut Pasteur du Brabant, Brussels, Belgium (Sprecher, Cogniaux, Thiry). Patients and staff from a Belgian dialysis unit were tested for human T- cell lymphotropic virus type [II (HTLV-II) antibodies. Eight of 100 patients had HTLV-II antibodies; in five of these patients, past or present infection with HTLV-III was confirmed by other tests. The putative source of HTLV-III was unrelated to dialysis in two patients, whereas blood transfusion was the most likely cause of contamination in the others. No staff member was positive for HTLV-II. The authors state that the lack of seropositivity among staff members confirms that the risk of nosocomial infection with HTLV-III is low if precautions similar to those recommended for the control of hepatitis B infection are used. This study involved HTLV-II antibody testing of dialysis patients and dialysis unit staff and investigation of possible source of exposure. Positivity for antibodies to HTLV-II was assessed by enzyme-linked immunosorbent assay with Western blot confirmation. Positive patients were investigated for risk factors for AIDS and took part in further blood tests and virological studies. A total of 100 dialysis patients and 49 unit staff in a Brussels dialysis unit were studied. 1) Transmission: Blood Transfusion and Blood Products (IIC), 2) Transmission: Health Care Accidents (IIE), 3) Geographic Trends: Europe (Belgium) (I1B4) 2C-Gol-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Peterman, Thomas A., MD, MSc; Lang, Gordon R., MD; Mikos, Norine J., RN; Solomon, Steven L., MD; Schable, Charles A., MS; Feorino, Paul M., PhD; Britz, Judith A., PhD; Allen, James R., MD, MPH. HTLV-III/LAV Infection in Hemodialysis Patients. Journal of the American Medical Association, 2 May 1986, Vol. 255, No. 17: 2324-2326. AIDS Branch, Division of Viral Diseases (Peterman, Feorino, Allen, Schable), and Hospital Infections Program (Solomon), Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; Neomedica Dialysis Centers, Chicago, Illinois (Lang, Mikos); Electro- Nucleonics Inc., Columbia, Maryland (Britz). This study was undertaken to ascertain the potential for human T-cell lymphotropic virus type III (HTLV-II) transmission in dialysis centers, where the blood of patients with impaired kidney function is filtered and cleared of toxins and wastes. Twenty-five of 520 (4.8%) hemodialysis patients were found to be blood test positive for HTLV-III antibodies. Four had high reactivity on enzyme immunoassay (EIA) and positive results of Western blot tests, and one of the four had a positive HTLV-III culture. The remaining 21 positive subjects had low reactivity on EIA, negative results in Western blot tests, and negative cultures. All had received blood transfusions, and 19 had antibodies to antigens associated with the cell line used to propogate HTLV-III for the serologic tests. HTLV-II was not found to have been transmitted in the dialysis centers. Frequent blood transfusion places dialysis patients at risk for HTLV-III infection, but may more commonly lead to false-positive results of EIA tests. The initial EIA screening for HTLV-III antibodies was performed at a commercial laboratory. New blood specimens were sent for blinded repeat EIA testing with a commercial kit at the Centers for Disease Control. Positive specimens were retested by Western blot analysis. T- cell subset analysis was done for seropositive patients and seronegative controls. Specimens from seropositive patients were cultured for HTLV- III itself. Patient records were reviewed for age, sex, race, diagnosis, medication, length of time on dialysis, dialysis appointments missed due to hospitalization, number of renal transplants, and units of blood received in the dialysis center. Patients and staff members found to have positive HTLV-III EIA results were interviewed to determine whether they had risk factors for AIDS. Dialysis center records were reviewed for these patients and for seronegative controls who were matched for the dialysis center. A group of 25 hemodialysis patients and two dialysis center staff members reported to have positive HTLV-III EIA results were studied, as well as seronegative controls, matched by dialysis center. 1) Transmission: Blood Transfusion (Dialysis Centers) (IIC), 2) Blood Product Safety: Cause of False Negative Results (VBI) 2C-Pet-4 Author(s): Title: Source: Institution: Findings: Method: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Safety of Therapeutic Immune Globulin Preparations with Respect to Transmission of Human T-Lymphotropic Virus Type III/Lympha- denopathy-Associated Virus Infection. Morbidity and Mortality Weekly Report, 11 April 1986, Vol. 35, No. 14: 231-233. Centers for Disease Control, Atlanta, Georgia. Immunoglobulins produced by plasma fractionation have not been implicated in transmission of AIDS, although batches produced prior to 1985 were not screened for antibody to human T-cell lymphotropic virus type III (HTLV-II). Current epidemiologic and laboratory evidence shows that these preparations carry no discernible risk of AIDS. This report reviews the background of immunoglobulin production and screening for HTLV-III that has occurred since 1985. Since August 1983, the Centers for Disease Control (CDC) has enrolled 938 persons who have been exposed to blood or body fluids of AIDS patients in a prospective surveillance study. To date, 451 entrants have been followed up and tested for HTLV-III antibodies. Of these, 183 are health care workers who received immunoglobulins as prophylaxis against hepatitis B virus infection. One of these 183 recipients is now positive for HTLV-III, but no preexposure serum was available for this individual, and seropositivity may have predated the exposure to hepatitis (needlestick injury) and the immunoglobulin prophylaxis. No documented seroconversions have occurred in any of 183 health care workers studied. Other studies have reported 16 subjects who received immunoglobulins who were strongly positive for HTLV-III antibody. Each patient had been given one to five ampules of immunoglobulins; 31 doses were administered to the 16 individuals. Low levels of passively acquired HTLV-II antibody were detected shortly after injection, but reactivity did not persist over time. Six months after injection, none of the 16 individuals had antibodies to HTLV-II. Other studies have yielded similar negative results. CDC information for 10,227 AIDS patients provides data on 358 patients (4%) who reported past treatment with immunoglobulin. All but seven of these were also members of high-risk groups for AIDS. The percentage of patients with no recognized risk factors for AIDS was not significantly different among those who received immunoglobulins and those who did not. Recent laboratory studies conducted by the Food and Drug Administration show that the margin of safety based on the removal of HTLV-II infectivity by the fractionation process in the production of immunoglobulins is extremely high. This report reviews relevant epidemiological and laboratory studies, including a study conducted by the CDC in which health care workers 2C-Cen-5 receiving immunoglobulins for hepatitis prophylaxis were followed for evidence of HTLV-III infection. Sample Size: This review includes reports from CDC studies and surveillance efforts, with sample sizes specified above. Policy Keys: 1) Transmission: Blood Products (immunoglobulins) (IIC), 2) Transmission: Health Care Accidents (IIE) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Giudizi, M.G.; Biagiotti, R.; Almerigogna, F.; Mazzetti, M.; Alessi, A.; Massai, G.; Longo, G.; Scano, G.; Morfini, M.; Romagnani, S. HTLV-II Seropositivity in Symptom-Free Italian Haemophiliacs: Correlation with Consumption of Commercial Concentrate and Abnormalities of T and B Lymphocytes. Scandinavian Journal of Haematology, 1986, Vol. 36, No. 2: 198-202. Division of Allergology and Clinical Immunology, University of Florence (Giudizi, Biagiotti, Almerigogna, Mazzetti, Alessi, Romagnani); Haemophilia Centre, Division of Haematology, Florence (Longo, Morfini); Division of Allergology and Clinical Immunology, University 'La Sapienza', Rome, Italy (Scano). Symptom-free European hemophiliacs exposed to blood clotting-factor VIII concentrate imported from the U.S. were tested for immunologic abnormalities in T- and B-cell function and for the presence of antibody to human T-cell lymphotropic virus type III (HTLV-II). Of 74 apparently healthy hemophiliacs tested, 23 (31%) had an abnormally low helper/suppressor T-cell ratio (less than 1.0). A large proportion had increased levels of serum immunoglobulin and circulating immune complexes. In addition, 38% had antibody to HTLV-III in their blood serum. HTLV-II seropositivity was significantly associated with the amount of clotting-factor concentrate consumed. A strong association between HTLV-III seropositivity and some T-cell abnormalities, such as reduced helper/suppressor T-cell ratios and decreased number of helper T cells, was also demonstrated, while no difference between seropositive and seronegative patients in the absolute number of suppressor T cells was found. Patients were examined and blood samples were drawn. T-cell subpopulations were counted by indirect immunofluorescence with OKT 3, OKT4, and OKT8 monoclonal antibodies. Antibody to HTLV-III structural proteins was assayed by indirect immunofluorescence. Information on replacement therapy between 1981 and 1984 was obtained from the hospital or patient records. A total of 74 consecutive hemophiliacs (62 with hemophilia A and 12 with hemophilia B) at the hemophilia center in Florence, Italy, were examined. Commercial clotting-factor concentrates manufactured from large plasma pools in the U.S. were used by all. None was known to be homosexual or an intravenous drug abuser. Control subjects consisted of 47 healthy volunteer members of the laboratory staff, their parents, and their children. 1) Transmission: Blood Products (IIC), 2) Immunological Aspects (IIE), 3) Populations: Hemophiliacs (IA3), 4) Geographic Trends: Europe (Italy) (IBY) 2C-Giu-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Verani, Paola; Mariani, Guglielmo; Mannucci, Pier M.; De Rossi, Giulio; Nicoletti, Loredana; Titti, Fausto; Falcione, Emanuela; Pasqualetti, Daniela; Ammassari, Michele; Gringeri, Alessandro; Mandelli, Franco; Rossi, Giovanni B. Prevalence of HTLV-III/LAV Antibodies in Italian Asymptomatic Hemophiliacs Given Commercial Concentrates of Factors VIII and IX. Journal of Medical Virology, 1986, Vol. 19: 143-149. Department of Virology, Istituto Superiore di Sanita, Rome, Italy (Verani, Nicoletti, Titti, Rossi); Department of Human Biopathology, Section of Hematology, University "La Sapienza", Rome, Italy (Mariani, De Rossi, Falcione, Pasqualetti, Mandelli); A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Ill Clinical Medicine, University and Maggiore Hospital, Milan, Italy (Mannucci, Ammassari, Gringeri). This study examined a group of 222 Italian patients with hemophilia A or B who were given only American plasma for serological and immunologi- cal features associated with AIDS or AIDS-related complex (ARC). Seventeen of 54 hemophiliacs (31%) tested for antibody to human T-cell lymphotropic virus type III (HTLV-II) were positive in 1983, 32 of 100 (32%) tested were positive in 1984 and 57 of 133 (43%) were positive in 1985. An increase in seropositivity from 1983 to 1985 was evident. This finding was independent of the type of hemophilia (A or B) but directly correlated to the amount of concentrate administered in the previous year. Immunological data showed that seropositivity was significantly associated with a low helper/suppressor T-cell ratio and with a reduced helper T-cell subpopulation. Data for 47 hemophiliacs tested in both 1984 and 1985 showed that 100% (seven of seven) of those negative in 1984 and multiply transfused during the ensuing year had seroconverted by 1985, whereas 33% (6 of 18) of those not multiply transfused had seroconverted. Blood samples were obtained from all patients and tested for serological and immunological evidence of AIDS or ARC. The study included 222 patients (175 with hemophilia A and 47 with hemophilia B) enrolled during the yearly checkup in hemophilia centers in Milan and Rome, Italy. All patients were clinically well, without any symptoms of AIDS or ARC, and all patients had received commercial factor VIII or factor IX concentrates made with plasma from the U.S. Patients were evaluated before the introduction of heat-treated concentrates in [taly in December 1984. 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3), 3) Geographic Trends: Europe (Italy) (IB4) 2C-Ver-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Peterman, Thomas A., MD, MSc; Jaffe, Harold W., MD; Feorino, Paul M., PhD; Getchell, Jane P., DrPH; Warfield, Donna T.; Haverkos, Harry W., MD; Stoneburner, Rand L., MD, MPH; Curran, James W., MD, MPH. Transfusion-Associated Acquired Immunodeficiency Syndrome in the United States. Journal of the American Medical Association, 22/29 November 1985, Vol. 254, No. 20: 2913-2917. Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Peterman, Jaffe, Feorino, Getchell, Haverkos, Curran, Warfield); New York City Department of Health, New York (Stoneburner). By 15 August 1985, 194 cases of possible transfusion-associated AIDS had been reported to the Centers for Disease Control (CDC). Cases received their transfusions in 30 states, although 38% of the cases were transfused in New York or California. Sixty percent of tranfusion-related cases occurred in males, and infants accounted for 10% of these cases, suggesting an increased susceptibility to developing AIDS. Investigations l to 6 years after the transfusion have identified high-risk donors for 47 cases. Of the 47 high-risk donors tested, 40 were positive for antibodies to HTLV-II, including 5 with no risk factors for AIDS. HTLV-II was isolated from 23 of 26 seropositive high-risk donors, most of whom remained asymptomatic. Blood components that transmitted HTLV-II included red cells, platelets, plasma, and whole blood. The time from transfusion to diagnosis of AIDS ranged from 4 to 84 months. The authors expect that the risk of developing AIDS after a blood transfusion has been low and will be lowered further by using both self-deferral and antibody screening. This study was a retrospective follow-up of possible transfusion- associated cases of AIDS. AIDS victims or close relatives were interviewed and hospital records reviewed when possible. Blood donors were interviewed with a standard questionnaire and examined for lymphadenopathy and skin lesions. Blood specimens from blood donors and recipients were tested by enzyme-linked immunosorbent assay, with an optical density of greater than 0.249 considered reactive and less than 0.151 considered nonreactive; specimens giving intermediate results were retested for confirmation. A total of 194 possible transfusion-associated cases of AIDS reported to the CDC by 15 August 1985 were studied. Cases met all of the following criteria: AIDS by CDC definition, low helper/suppressor T-cell ratio (if tested), transfusion of blood or single-donor blood product between 1978 and onset, and no other known risk factor for AIDS. 1) Transmission: Blood Transfusion (IIC), 2) Incubation Period (IIIC), 3) Blood Product Safety: Screening and Self-Deferral (VB2), 4) Geographic Trends: U.S. (IB1) 2C-Pet-8 Author(s): Title: Source: Institution: Findings: Method: Allain, J.P.; Courouce, A.M.; Muller, J.Y.; Bach, J.F.; Boiteux, F.; Gazengel, C.; Girot, R.; Torchet, F.; Bardos, P.; Goudeau, A.; Lesage, G.; Bastit, D.; Bosser, C.; Frommel, D.; Guerois, C.; Leroy, J.; Larrieu, M.J.; Laurian, Y.; Lambert, T.; Montagnier, L.; Noel, B.; Paitre, M.Ly Revillard, J.P.; Cordier, G.; Vincent, S.; Lafont, S.; Rouzioux, C.; Brun- Vezinet, F.; Verroust, F. Immunologic and Virologic Status of Multitransfused Patients: Role of Type and Origin of Blood Products. Blood, October 1985, Vol. 66, No. 4: 896-901. Centre National de Transfusion Sanguine, Paris (Allain, Courouce, Muller); Hopital Necker-Enfants Malades, Paris (Bach, Boiteux, Gazengel, Girot, Torchet); Hopital Bretonneau, Tours (Bardos, Goudeau, Lesage); Centre Regional de Transfusion Sanguine, Rouen (Bastit); Croix Rouge Francaise, St. Alban-Leysse (Bosser); INSERM & Hopital de la Salpetriere, Paris (Frommel); Hopital Trousseau, Tours (Guerois, Leroy); INSERM & Hopital de Bicetre, Kremlin Bicetre (Larrieu, Laurian, Lambert); Institut Pasteur, Paris (Montagnier); Centre de Transfusion Sanguine, Chambery (Noel); Centre de Transfusion Sanguine, Le Havre (Paitre); INSERM & Hopital E. Herriot, Lyon (Revillard, Cordier, Vincent, Lafont); Hopital Claude Bernard, Paris (Rouzioux, Brun- Vezinet); Croix Rouge Francaise, La Queue les Yvelines, France (Verroust). To determine whether clinical, immunologic, and virologic status differed among French hemophiliacs depending on the origin (local or U.S.) of their clotting factor concentrates, patients were divided into five groups according to the type of blood product they received. The groups were local factor VIII, a mixture of local and imported factor VIII, imported factor IX, local factor IX, and washed red blood cells. The overall prevalence of immunoglobulin G antibodies to lymphadenopathy- associated virus (LAV) was 45%. The highest rate was observed in hemophiliacs who received factor VIII concentrates collected mainly in America; intermediate values were found for hemophiliacs receiving local factor VIII and factor [X concentrates; and the lowest values were in patients treated with washed red blood cells. Lymphadenopathy, decreased skin hypersensitivity reactions, decreased total lymphocyte count, and altered helper/suppressor T-cell ratios occurred at significantly higher rates in patients positive for LAV antibody. These abnormalities were also encountered, however, in seronegative patients. A correlation between treatment intensity and immunologic disturbances was found in factor VIII recipients regardless of LAV antibody status. Full blood counts and total lymphocyte counts were calculated for each serum sample, using monoclonal antibody OKT3 for total T cells, OKT4 for helper cells, and OKT8 for suppressor cells. An enzyme-linked immunosorbent assay was used to test for antibodies to LAV. Tests were 2C~-A11-9 Sample Size: Policy Keys: also run for antibodies to cytomegalovirus (CMV), Epstein-Barr virus, hepatitis A and B viruses, and human T-cell lymphotropic virus type I (HTLV-D). Group I consisted of 80 hemophilia A patients (60 severe and 20 mild or moderate), ranging in age from | to 67 years (median, 15.4). These patients were treated exclusively with factor VIII preparations made from plasma collected in France. Group II comprised 219 patients with hemophilia A (191 severe, 28 moderate or mild), aged | to 63 years (median, 15.9). These patients were treated with a mixture of imported factor VIII mostly manufactured from American plasma. Group III included 48 patients with severe hemophilia A who had been receiving mostly factor IX concentrates since 1981. Group IV comprised 58 hemophilia B patients (40 severe, 18 moderate or mild), aged 2 to 66 years (median, 20.1). All of these patients had been treated only with French factor IX concentrates. Group V consisted of 20 patients with congenital anemias. This group was included to compare the other groups with a population of multitransfused patients who did not receive plasma derivatives. The age range was 5 to 25 years (median, 13). 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3), 3) Geographic Trends: Europe (France) (IB4) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Biberfeld, Gunnel; Bottiger, Blenda; Karlsson, Anders; Sandstrom, Erik; Morfeldt-Mansson, Linda; Blomback, Margareta; Nilsson, Inga-Marie; Wiechel, Barbro; Saxinger, Carl; Gallo, Robert. HTLV-II Infection in Homosexuals and Hemophiliacs in Sweden. Cancer Research, September 1985, Vol. 45 (Suppl.): 4609s-461 Is. Department of Immunology, National Bacteriological Laboratory, Stockholm (Biberfeld, Bottiger); Department of Dermatology and Venerology, Sodersjukhuset, Stockholm (Karlsson, Sandstrom); Department of Infectious Diseases, Karolinska Institute, Roslagstull Hospital, = Stockholm = (Morfeldt-Mansson); Coagulation Laboratory, Karolinska Hospital, Stockholm (Blomback); Coagulation Laboratory, Malmo General Hospital, Malmo, Sweden (Nilsson); Stockholm City Blood Center, Stockholm, Sweden (Wiechel); Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Saxinger, Gallo). Groups of Swedish homosexual men, hemophiliacs, and male blood donors were tested for antibodies to human T-cell lymphotropic virus type III (HTLV-II). HTLV-II antibodies were found in 13 of 13 (100%) homosexual men with AIDS, in 63 of 67 (94%) homosexual men with lymphadenopathy, in 17 of 45 (38%) symptomatic homosexual men, and in 6 of 78 (8%) asymptomatic homosexual men. Antibodies were not found in any of 108 male blood donors. Homosexual men with positive findings had lower helper/suppressor T-cell ratios than homosexual men without HTLV-II antibodies. Among hemophilia A patients, HTLV-II antibodies were present in 40 of 48 (83%) cases treated with American factor VIII concentrate and in 17 of 29 (59%) cases treated with both American and Swedish concen- trates. No HTLV-II infection was found in the 13 hemophiliacs treated exclusively with Swedish factor VIII. Of 21 hemophilia B patients treated with Swedish factor IX concentrate, all were negative, and one of three hemophilia patients treated with imported factor [X concentrate was positive for HTLV-II infection. Helper/suppressor T-cell ratios were lower in HTLV-Ill-positive than in HTLV-III-negative hemophilia A patients. This was a case-control seroepidemiological study of homosexual male and hemophiliac residents of Sweden. Blood specimens collected in 1983 and 1984 were tested for antibodies to HTLV-II by enzyme-linked immunosorbent assay, with cases having values at least three times over that of a standard negative control serum confirmed by Western blotting. T-cell subsets were determined by direct or indirect immuno- fluorescence. A total of 203 homosexual men and 114 hemophiliacs resident in Sweden were tested. The homosexual group included 13 men with AIDS (as defined by the Centers for Disease Control), 67 men with persistent generalized lymphadenopathy, 45 other symptomatic men, and 78 asymptomatic men. The hemophiliac group included 90 patients with hemophilia A (61 adults and 29 children aged 15 years or less) and 24 2C-Bib-10 patients with hemophilia B (20 adults and 4 children). A control group of 108 Swedish male blood donors was also studied. Policy Keys: 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs, Homosexuals ([A3,1), 3) Geographic Trends: Europe (Sweden) (IB4), 4) Immunological Aspects (IIE) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Gjerset, George F.; McGrady, Gene; Counts, Richard B.; Martin, Paul J.; Jason, Janine; Kennedy, Susan; Evatt, Bruce; Hansen, John A. Lymphadenopathy-Associated Virus Antibodies and T Cells in Hemo- philiacs Treated with Cryoprecipitate or Concentrate. Blood, September 1985, Vol. 66, No. 3: 718-720. Puget Sound Blood Center, Fred Hutchinson Cancer Research Center, and University of Washington, Seattle; Division of Host Factors, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. This study evaluated T-cell subsets and T-cell function in hemophiliac patients receiving commercial concentrates or single-donor cryoprecipi- tate (cold-precipitated clotting factor) in relation to the presence or absence of lymphadenopathy-associated virus (LAV) antibodies. Antibod- ies to LAV were detected in 53% of all 48 patients in 1983 and in 63% in 1984. More of the 33 patients treated with commercial concentrate were positive (65% in 1983, 77% in 1984) compared with the 15 patients treated only with single-donor cryoprecipitate (31% in 1983, 40% in 1984). Patients using any concentrate since 1981 were 3.9 times more likely to convert from negative to positive status than patients using cryoprecipitate only. The rate of conversion for these two groups was 71% and 18%, respectively. LAV antibody-positive patients were more likely to have a significant reduction in the ratio of helper to suppressor T cells, absolute numbers of helper cells, and T-cell function. Except for two individuals, patients remained well and free of unusual infections or other clinical evidence of immunodeficiency. Patient comparisons are based on assessments of T-cell subsets and function. Helper and suppressor T cells were identified by direct immunofluorescence with Leu-3 and Leu-2-equivalent monoclonal anti- bodies. T-cell function was assessed by testing mitogen-induced proliferation of peripheral blood mononuclear cells. LAV antibodies were assessed by Western blot. The study included 48 hemophiliac patients with factor VIII or factor IX deficiency treated at the Puget Sound Blood Center in Seattle, Washington. Forty-three were studied in January 1983 and 41 in January 1984. Of 42 patients with factor VIII deficiency, l4 were moderately affected and 27 were severely affected. The other six patients had severe factor IX deficiency. Patients were grouped according to treatment: 15 receiving cryoprecipitate only, 19 receiving cryoprecipitate and concentrate, and l4 receiving concentrate only. The median age of the patients was 28 years and was comparable for all treatment groups. Controls consisted of healthy volunteers, with a median age of 36 years (range, 13 to 47), with no known risk factors for AIDS. 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3) 2C-Gje-11 Author(s): Title: Source: [nstitution: Findings: Method: Dienstag, Jules L., MD; Werner, Barbara G., PhD; McLane, Mary F.; Snydman, David R., MD; Grady, George F., MD; Craven, Donald E., MD; Crumpacker, Clyde S., MD; Polk, B. Frank, MD; Platt, Richard, MD; Allan, Jonathan, DVM; Essex, Max, DVM, PhD. Absence of Antibodies to HTLV-III in Health Workers after Hepatitis B Vaccination. Journal of the American Medical Association, 23/30 August 1985, Vol. 254, No. 8: 1064-1066. Boston Inter-Hospital Hepatitis B Vaccine Study Group [Medical Services, Massachusetts General Hospital (Dienstag); State Laboratory Institute, Department of Public Health, Commonwealth of Massachusetts (Werner, Snydman, Grady); Department of Medicine, Tufts-New England Medical Center (Snydman); Department of Medicine, Boston University Hospital (Craven); Department of Medicine, Boston City Hospital (Craven); Department of Medicine, Beth Israel Hospital (Crumpacker); Department of Medicine, Brigham and Women's Hospital (Polk); Department of Medicine, New England Deaconess Hospital (Platt)]; Department of Cancer Biology, Harvard School of Public Health (McLane, Allan, Essex); Department of Medicine, Harvard Medical School (Dienstag, Crum- packer, Polk, Platt); Department of Medicine, Tufts University School of Medicine (Werner, Snydman, Grady); Department of Medicine, Boston University School of Medicine (Craven), Boston, Massachusetts. Since a proportion of the plasma used in a hepatitis B vaccine produced in the U.S. is obtained from homosexual men who may be at risk for AIDS, this study tested serum samples of plasma recipients 15 months after vaccination for antibodies to human T-cell lymphotropic virus type II (HTLV-II). Half of a group of 200 health care workers received inactivated hepatitis B vaccine lots made from plasma collected between 1977 and 1979, while the other half received placebo injections. None of the 200 subjects had serological evidence of HTLV-II infection. Although the prevalence of AIDS and HTLV-III was not as great in 1979 as it is now, the authors conclude that the hepatitis B vaccine is apparently safe and does not transmit AIDS, despite high-risk donors, because data failed to demonstrate a risk of infection with HTLV-II in recipients of vaccine obtained from persons at risk for AIDS. In addition, both lots investigated in this study and commercial lots manufactured in 1981 were subjected to the same elaborate three-step inactivation process as well as exhaustive safety testing, including inoculation of chimpanzees, which are susceptible to AIDS, without evidence of transmission of HTLV-IIIL. Half of the subjects had received a full course of three 20 u injections of inactivated hepatitis B vaccine and half received a full course of three placebo injections. The plasma from which these vaccine lots were purified had been collected between 1977 and 1979. Serum samples obtained 15 months after initial vaccination, beginning in November 1980, were selected. For participants whose serum samples showed any questionable anti-HTLV-III reactivity, prevaccination serum samples were tested as well. Samples were tested by indirect membrane 2C-Die-12 Sample Size: Policy Keys: immunofluorescence and samples apparently positive by immuno- fluorescence staining were retested by a radioimmunoprecipitation assay. Serum samples were selected by consecutive code numbers and without information about participant identity from 200 health workers involved in a recently reported Boston Inter-Hospital Hepatitis B Vaccine Study. 1) Transmission: Hepatitis B Vaccine (IIC), 2) Blood Product Safety: Inactivation of Virus (VB3) 3) Populations: Health Care Workers (IA7) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jaffe, Harold W., MD; Sarngadharan, Mangalasseril G., PhD; DeVico, Anthony L.; Bruch, Lilian; Getchell, Jane P., DrPH; Kalyanaraman, Vaniambadi S., PhD; Haverkos, Harry W., MD; Stoneburner, Rand L., MD; Gallo, Robert C., MD; Curran, James W., MD. Infection with HTLV-III/LAV and Transfusion-Associated Acquired Immunodeficiency Syndrome: Serologic Evidence of an Association. Journal of the American Medical Association, 9 August 1985, Vol. 254, No. 6: 770-773. Division of Viral Diseases, Center for Infectious Diseases, and Division of Field Services, Epidemiology Program Office, Centers for Disease Control, Atlanta, Georgia (Jaffe, Getchell, Kalyanaraman, Haverkos, Stoneburner, Curran); Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland (Sarngadharan, DeVico, Bruch); New York City Department of Health, New York (Stoneburner); Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Gallo). Patients with transfusion-associated AIDS and their blood donors were studied for serologic evidence of infection with human T-cell lymphotropic virus type I[lI/lymphadenopathy-associated virus (HTLV- III/LAV). All 19 patients with AIDS were seropositive. In all 28 donor sets containing high-risk donors, at least one donor was seropositive. Of 255 donors not considered high risk, two were positive for HTLV-III/LAV antibody. When 30 seropositive high-risk donors were evaluated an average of 29 months after donation, 4 (13%) had developed AIDS and 8 (27%) had lymphadenopathy. The authors conclude that HTLV-III/LAV causes AIDS and that seropositive high-risk donors may be at relatively high risk for developing AIDS and related conditions, as may the recipients of their blood. This study traced donors providing blood used by patients who later developed AIDS, tested donors for HTLV-III/LAV antibody by enzyme- linked immunosorbent assay, and followed them for development of AIDS. Patients with transfusion-associated AIDS were also tested for antibody to HTLV-III/LAV. A total of 308 specimens were studied from 19 transfusion-related AIDS cases who had no risk factor other than transfusion in the past 5 years, 28 sets of their high-risk blood donors, and 255 low-risk donors. 1) Transmission: Blood Transfusion (IIC), 2) Disease Stages (IIIC) 2¢c-Jaf-13 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Feorino, Paul M., PhD; Jaffe, Harold W., MD; Palmer, Erskine, PhD; Peterman, Thomas A., MD; Francis, Donald P., MD; Kalyanaraman, V.S., PhD; Weinstein, Robert A., MD; Stoneburner, Rand L., MD; Alexander, W. James, MD; Raevsky, Cathy; Getchell, Jane P., DrPH; Warfield, Donna; Haverkos, Harry W., MD; Kilbourne, Barbara W., MPH; Nicholson, J.K.A., PhD; Curran, James W., MD. Transfusion-Associated Acquired Immunodeficiency Syndrome: Evidence for Persistent Infection in Blood Donors. The New England Journal of Medicine, 16 May 1985, Vol. 312, No. 20: 1293-1296. AIDS Program, Centers for Disease Control, Atlanta, Goergia (Curran); Department of Internal Medicine, Michael Reese Hospital, Chicago, Illinois; New York City Department of Health, New York; Jefferson County (Alabama) Department of Health, Birmingham; Colorado Department of Health, Denver. To determine how long infection persists in high-risk donors and to correlate infection with seropositivity, this study attempts to isolate human T-cell lymphotropic virus type IlI/lymphadenopathy-associated virus (HTLV-III/LAV) from patients with transfusion-associated AIDS and high-risk donors identified in these investigations. HTLV-III/LAV was found in 22 of 25 identified high-risk blood donors from 12 to 52 months (mean, 28) after they had donated blood. Similar studies were conducted of six of 24 patients with AIDS who had received donations from this group. Patients who received blood from these donors tested positive for antibodies to the virus between 14 and 37 months (mean, 26) after transfusion. The median time from transfusion to diagnosis of AIDS was 29 months for adults and 14 months for children. The study suggests that isolation of HTLV-III/LAV from both blood donors and their recipients indicates that HTLV-III/LAV plays a causative role in the development of AIDS and that infection may be persistent and asymptomatic. The authors support the use of blood-screening techniques as a supplement to efforts to prevent transfusion-associated AIDS. AIDS patients with no known risk factors who had received blood or blood products between 1978 and the onset of disease were categorized as transfusion-associated cases. Their blood donors were identified and given confidential interviews and physical exams, and blood samples were drawn for T-cell subset analyses. Donors were defined as high risk if they had AIDS or AIDS-related complex, had a helper/suppressor T-cell ratio of less than 1.0, or belonged to a known at-risk group. A direct immunofluorescence test was performed, as well as enzyme-linked immunosorbent assay. Seven patients with transfusion-associated AIDS and 27 high-risk blood donors were identified. Complete cultures were available for 6 patients with AIDS and 25 donors. 1) Transmission: Blood Transfusion (IIC), 2) Incubation Period and Disease Progression (IIIC) 2C-Feo-14 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kloster, Bruce E., MD; Tomar, Russell H., MD; Stockman, James A., III, MD; Lamberson, Harold V., MD, PhD; Merl, Stuart A., MD; John, Patricia A., MS; Groth, Diane M., RN, CPNP; Poiesz, Bernard J., MD. Antibodies to Human T-Cell Lymphotropic Virus-I Membrane Antigens and Inverted T4/T8 Ratios in Hemophiliacs. American Journal of Clinical Pathology, April 1985, Vol. 83, No. 4: 450- 456. Departments of Pathology, Division of Clinical Pathology, Medicine, and Pediatrics, Upstate Medical Center, Syracuse; American Red Cross, Syracuse; Barbara Kopp Research Institute, Syracuse, New York. This study examined blood serum samples from 71 AIDS patients and 46 hemophiliac children for the presence of human T-cell lymphotropic virus (HTLV) antibodies. Thirty-seven of 71 (52%) AIDS patients and 7 of 46 (15%) hemophiliac patients had high HTLV antibody levels. None of 78 control subjects had these high antibody levels. All seven of the hemophiliac patients used factor VIII concentrates, and all had lowered T-cell ratios. No relationships were found between lowered T-cell ratios and the presence of cytomegalovirus, Toxoplasma gondii, or hepatitis B virus. The authors conclude that these findings provide further evidence that HTLV-like organisms cause AIDS and that it can be transmitted via blood products. This was a case-control study of AIDS patients and hemophiliac children, in which HTLV antibodies and T-cell ratios were measured. Antibodies to HTLV-associated membrane antigens were measured in an indirect membrane Immunofluorescence assay with the reference HTLV-I- infected cell line HUT-102-B2. Lymphocyte subpopulations were measured by indirect membrane immunofluorescence with monoclonal antibodies T4 and T8. Cytomegalovirus, T. gondii, and hepatitis B virus antigens and antibodies were measured by enzyme-linked immunosorbent assay. Serum samples were obtained from 71 AIDS patients, 52 from the Centers for Disease Control (6 females, 46 males) and 19 (1 female, 18 males) from the Upstate Medical Center, Syracuse, New York, and from 46 hemophiliac children (aged 16 months to 19 years) and 78 healthy controls (aged 18 months to 78 years) from the Pediatric Hematology Clinic at the Upstate Medical Center. Controls were drawn from laboratory or hospital workers and their children. 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3) 2C-Klo-15 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Rouzioux, Ch., PhD; Brun-Vezinet, F., MD; Courouce, A.M., PhD; Gazengel, C., MD: Vergoz, D., MD; Desmyter, J., MD; Vermylen, J., MD; Vermylen, C., MD; Klatzmann, D., MD; Geroldi, D., MD; Barreau, C., PhD; Barre-Sinoussi, F., PhD; Chermann, J.C., PhD; Christol, D., MD; Montagnier, L., MD. Immunoglobulin G Antibodies to Lymphadenopathy-Associated Virus in Differently Treated French and Belgian Hemophiliacs. Annals of Internal Medicine, April 1985, Vol. 102, No. 4: 476-479. The Laboratoire Central de Virologie, Hopital Claude Bernard; Centre National de Transfusion Sanguine; Centre d'Hemophilie, Hopital Necker; Laboratoire d'mmunologie, Nephrologique et Transplantation, Hopital Pitie-Salpetriere; and Department de Virologie, Institut Pasteur, Paris, France; Rega Institute and Faculty of Medicine, Leuven, Belgium; and Universita di Pavia, Pavia, Italy. A survey was conducted to detect antibodies to the lymphadenopathy- associated virus (LAV) in the blood of two groups of French hemophiliacs and one group of Belgian hemophiliacs who differed in their mode of treatment and the origin of blood products, and in a control group. Seropositivity for LAV occurred more frequently (58.9%) in French patients who had been heavily transfused with blood products of French and foreign origin than in patients who had been less frequently transfused (10.3%) or in Belgians treated only with local blood products (3.4%). In a healthy French control group, only one person in 330 was found to be seropositive to LAV. The type of hemophilia (A or B) these patients had did not influence seropositivity to LAV, but the amount of blood products they had received did influence seropositivity to LAV. Results indicate that LAV is transmitted via blood-derived products. The three sample groups were broken down into those with hemophilia A and hemophilia Bj; these six groups were further broken down into those receiving less than 800 U of blood-clotting factor VIII or clotting factor IX per kg of body weight per year and those treated with 800 U or more of these factors. Blood tests for LAV used enzyme-linked immunosorbent assay techniques. A total of 245 European hemophiliacs were studied: group [ (128) of French patients from a Parisian hemophilia center, group II (58) of French patients from a different Parisian medical center, and group III (59) of native Belgian patients. The control group consisted of 300 unselected French blood donors and 30 laboratory workers. 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3), 3) Geographic Trends: Europe (France, Belgium) (IB4) 2C-Rou-16 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Goedert, James J.; Sarngadharan, M.G.; Eyster, M. Elaine; Weiss, Stanley H.; Bodner, Anne J.; Gallo, Robert C.; Blattner, William A. Antibodies Reactive with Human T Cell Leukemia Viruses in the Serum of Hemophiliacs Receiving Factor VIII Concentrate. Blood, February 1985, Vol. 65, No. 2: 492-495. Environmental Epidemiology Branch and Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland; Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland; Division of Hematology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania; Biotech Research Laboratories, [nc., Rockville, Maryland. This study evaluates the frequency of antibodies to the AIDS virus (human T-cell lymphotropic virus, HTLV-III) in the blood of hemophiliac patients who had received transfusions with several different types of blood products. Ninety percent of patients frequently transfused with a concentrate of factor VIII had antibodies to HTLV-III. Fifty percent of those treated with both factor VIII and factor [IX concentrates had antibodies to HTLV-III. No hemophiliac patients treated with factor [X concentrate alone, volunteer plasma, or cryoprecipitate (a cold- precipitated, usually single-donor, preparation of blood-clotting factors) showed antibodies to HTLV-II. Two of the patients with antibodies to HTLV-II have developed AIDS-related illness. The predominant antibody specificities appear directed against p24 and p41, the presumed core and envelope antigens of HTLV-II, suggesting that factor VIII concentrate may transmit the antigens. The presence of HTLV-II in clotting factor concentrate and the effectiveness of screening and viral neutralization procedures remain to be determined. This was a prevalence study conducted between September 1982 and April 1984 at the Milton S. Hershey Medical Center, Hershey, Pennsylvania. Blood samples from hemophiliac patients who had been transfused with various blood-clotting factor preparations were frozen and then blindly tested for HTLV-II antibodies by the Western blot technique, with a ratio of >5 considered positive. A total of 109 hemophiliac patients at the Milton S. Hershey Medical Center hemophiliac clinic in Hershey, Pennsylvania, were studied. Of the group, 69 were hemophilia A patients who had ever received factor VIII but not factor IX concentrate; a subset of 48 of these patients received factor VIII concentrate at least twice a month. Six hemophilia A patients were treated with both factor VIII and [IX concentrates. Twelve hemophilia B patients were treated with factor [X concentrate, and 22 patients were treated only with cryoprecipitate. 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3) 2C-Goe-17 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Erfle, V.; Hehlmann, R.; Mellert, W.; Goebel, F.D.; Rasokat, H.; Lechler, E.; Hellstern, P.; Kohler, M.; Seifried, E.; Heimpel, H. Prevalence of Antibodies to Human T-Lymphotropic Virus-III (HTLV-II) in Hemophiliacs and Other Patients Chronically Substituted with Blood Products. Blut, 1985, Vol. 51: 243-249. Abteilung fur Pathologie, Gesellschaft fur Strahlen- und Umwelt- forschung, Neuherberg (Erfle, Mellert); Medizinische Poliklinik, Ludwig- Maximilians-Universitat Munchen, (Hehlmann, Goebel); Hautklinik, Universitat Koln, (Rasokat); Medizinische Klinik, Universitat Koln, (Lechler); Abteilung fur Klinische Hamostaseologie und Transfusions- medizin, Universitatskliniken Homburg/Saar (Hellstern, Kohler); Zentrum Innere Medizin, Universitat Ulm, Federal Republic of Germany (Seifried, Heimpel). The prevalence of antibodies to human T-cell lymphotropic virus type III (HTLV-II) was determined in German hemophiliacs and other patients who received blood products and in blood donors in three German cities: Ulm, Cologne, and Homburg/Saar. Fifty-eight of 140 (41.4%) hemophil- lacs were seropositive, and in all cases for which the origin of blood factors given to these patients could be determined, the blood products came from the U.S. Two of 36 (5.6%) polytransfused patients, most with acute leukemias, who were transfused with blood products from local donors were positive for HTLV-II antibodies. None of the blood donors tested were positive for HTLV-III antibodies. Serum samples collected in the second half of 1984 had a four times higher proportion of positives than serum samples collected in the first half of 1983. Since treatment schedules, severity of cases, and requirement for coagulation factors were similar among the hemophiliac groups, this study indicates increasing HTLV-II contamination of blood- clotting factor products (and thus an increaseing number of infected hemophiliacs) over the years. The prevalence of antibodies to HTLV-II was determined by enzyme- linked immunosorbent assay (ELISA) and confirmatory tests (including the Western blot technique), and the results were compared for groups of hemophiliacs, polytransfused patients, and blood donors. The sample included 140 German hemophiliacs (35 from Ulm, tested January to May 1983; 64 from Cologne, tested January to June 1984; 23 from Homburg/Saar, tested September to October 1984; 17 from Homburg/Saar treated with heat-inactivated blood products, tested November 1984 to January 1985; and one, type A, from Reutlingen), 36 polytransfused patients (most with acute leukemias and aplastic anemias) who had received between 10 and 180 transfusions, and 237 blood donors (206 from Munich, and 31 who donated blood to the group of polytransfused patients). 2C-Erf-18 Policy Keys: 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3), 3) Geographic Trends: Europe (West Germany) (IB4) Author(s): Title: Source: Institution: Findings: Method: Sacks, Henry S., PhD, MD; Rose, David N., MD; Chalmers, Thomas C., MD. Should the Risk of Acquired Immunodeficiency Syndrome Deter Hepatitis B Vaccination?: A Decision Analysis. Journal of the American Medical Association, 28 December 1984, Vol. 252, No. 24: 3375-3377. Clinical Trials Unit (Sacks, Chalmers) and the Departments of Medicine (Sacks, Rose, Chalmers), Community Medicine (Rose), and Biomathematical Sciences (Sacks), Mount Sinai School of Medicine of The City University of New York, New York, New York. Fear that the AIDS causative agent contaminates the currently available hepatitis B vaccine stocks may have discouraged vaccine use. This study presents the findings of a decision analysis model formulated to compare the risk of death from hepatitis B and AIDS (in those vaccinated) with the risk of death from hepatitis B alone in those who wait 2 years for a synthetic vaccine to become available. Based on best estimates, among 100,000 people with a 5% annual risk of hepatitis B infection, such as surgeons, there would be 29 deaths without vaccination and 4 deaths with vaccination, all from hepatitis. Combining the probabilities that minimize the vaccine's benefits and maximize its risks (such as the highest likely rate of vaccine-induced AIDS), 10 persons would die of hepatitis without the vaccine and 10 would die with the vaccine (2 of hepatitis and 8 of AIDS). Conversely, combining probabilities that maximize the vaccine's benefits and minimize its risks, 95 persons would die without vaccination while just 5 would die with vaccination. Among 100,000 people with a 10% annual incidence of hepatitis B infection, such as dialysis patients, the benefit-risk ratio is even higher. Given an estimate of vaccine-induced AIDS of zero and a 95% confidence that the vaccine-induced AIDS rate is less than 8 per 100,000, the authors postulate that the rate would have to be considerably higher before postponement of vaccination for hepatitis B would be rational for those for whom vaccination has been recommended. The outcomes expected within 2 years for two alternative strategies -- using the current hepatitis B vaccine now or waiting 2 years -- were compared. The model applies to people for whom the vaccine has been recommended: health care personnel working in areas where hepatitis B is highly endemic (dialysis staff, surgeons, oral surgeons) and people with an especially high risk for hepatitis B (homosexually active men, intravenous drug abusers, institutionalized mentally retarded persons, hemophiliacs, and dialysis patients). Published rates of hepatitis B infection among these groups were converted to probabilities. Best-estimate analyses of the outcome of both strategies for hypothetical cohorts of 100,000 people with similar hepatitis B rates were performed. In addition, sensitivity analyses combining probabilities 2C-Sac-19 Sample Size: Policy Keys: at extremes of their reasonable ranges were performed to test whether the decision was sensitive to such variations. A case fatality rate for hepatitis B infection of 0.3% was used for the annual rate, and the range 0.1% to 1.0% was used in the sensitivity analysis. For the efficacy of the vaccine, 87.5% was used for the best estimate and a range of 80% to 95% was used in the sensitivity analysis. As of November 1984, 40,000 people had received the hepatitis B vaccine at least 27.5 months previously, and no case of AIDS had occurred in individuals who did not have other risk factors. Therefore, the best estimate of the vaccine-induced AIDS rate is zero, and one can be 95% confident that the highest likely rate is 8 cases per 100,000 population. The AIDS case fatality rate was calculated as 100%. Not applicable. 1) Transmission: Blood Products (Hepatitis B Vaccine) (IIC), 2) Populations: Health Care Workers (IA7) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Melbye, Mads; Madhok, Rajan; Sarin, Prem S.; Lowe, Gordon D.O.; Goedert, James J.; Froebel, Karin S.; Biggar, Robert J.; Stenbjerg, Stener; Forbes, Charles D.; Gallo, Robert C.; Ebbesen, Peter. HTLV-III Seropositivity in European Haemophiliacs Exposed to Factor VIII Concentrate Imported from the USA. The Lancet, 22/29 December 1984, Vol. 2, No. 8417/8: 1444-1446. Institute of Cancer Research, Radiumstationen, Aarhus, Denmark; University Department of Medicine, Royal Infirmary, Glasgow, United Kingdom; Environmental Epidemiology Branch and Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland; and Blood Bank, Aarhus Municipal Hospital, Aarhus, Denmark. Scottish and Danish hemophiliacs were tested for antibodies to human T- cell lymphotropic virus type II (HTLV-II). Since 1979 the Scottish patients had been treated largely with factor VIII concentrate produced in Scotland, whereas all but two of the Danish patients had received both locally prepared concentrate and commercial concentrate made from U.S. donor material. [t was found that 15.6% of Scottish and 59.1% of Danish hemophiliacs tested positive for HTLV-II antibodies. None of 11 hemophiliacs not treated between 1979 and 1984 was positive. Furthermore, 6.7% of 30 subjects who had been treated with locally produced concentrate only were antibody positive, compared with 39.7% of 58 subjects who had been treated with commercial concentrate. Among 52 users of both commerically and locally produced factor VIII concentrate, seropositivity was directly correlated with the use of commercial concentrate but not locally produced material. The authors conclude that European hemophiliacs were exposed to HTLV- [II via some factor VIII concentrates obtained from the U.S. This study consisted of antibody testing of European hemophiliacs, comparing those exposed to U.S.-produced factor VIII concentrates with those using only locally produced concentrates and those using both types of concentrates. Blood was taken from Danish hemophiliacs in Aarhus in April 1984 and frozen; blood was taken from Scottish hemophiliacs at Glasgow in December 1983 and July 1984. Antibody to HTLV-II was measured by enzyme-linked immunosorbent assay, with samples run in duplicate and results recorded as positive if the sample/background ratio was greater than 5. A total of 22 healthy Danish hemophiliacs and 77 healthy Scottish hemophiliacs were studied. 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3), 3) Geographic Trends: Europe (Scotland, Denmark) (IB4) 2C-Mel-20 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Kitchen, L.W.; Barin, F.; Sullivan, J.L.; McLane, M.F.; Brettler, D.B.; Levine, P.H.; Essex, M. Aetiology of AIDS--Antibodies to Human T-Cell Leukaemia Virus (Type III) in Haemophiliacs. Nature, 22 November 1984, Vol. 312: 367-369. Department of Cancer Biology, Harvard School of Public Health, Boston (Kitchen, Barin, McLane, Essex); Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester; New England Comprehensive Hemophiliac Center, and Department of Medicine, Worcester Memorial Hospital, Worcester, Massachusetts (Sullivan, Brettler, Levine). This study tracked seropositivity to human T-cell lymphotropic virus type [Il (HTLV-II) in 50 hemophiliacs over a 2-year period. Results indicate that exposure to HTLV-III is widespread among asymptomatic hemophil- lacs and may have increased from 1983 to 1984. Of 34 hemophiliacs tested during 1983, 18 (53%) tested positive for antibodies to HTLV-II; of 16 hemophiliacs tested during 1984, 15 (94%) tested positive. For the 33 (66% of the total sample) who tested positive, antigens most consistently detected included the following viral proteins: gp4l, gpl20, gpl60, p24, and p53. Other studies have found these proteins to be the most frequently detected by HTLV-IIl antibodies from AIDS patients. The control group tested antibody negative on both tests. The incubation period for AIDS following blood transfusion has been estimated to be 10 months to 4 years. The authors suggest further studies to (1) confirm this trend, (2) investigate whether a significant proportion of asymptomatic hemophiliacs are exposed to inactivated HTLV-III rather than a live virus, due to the manufacturing process of commercial factor VIII concentrate, and (3) to determine whether the presence of antibodies to HTLV-III indicates immunization, infection, or an asymptomatic carrier state in hemophiliacs. This prospective study of seroconversion in hemophiliacs used two tests. Blood sera were initially examined at 1:4 dilution by indirect membrane immunofluorescence on an HTLV-III-infected cell line (H9/HTLV-III) and an uninfected cell line (H9). Sera were then tested by radioimmuno- precipitation. Fifty hemophiliacs (aged | to 69 years, no median age given) from the New England Area Comprehensive Hemophiliac Center in Worcester, Massachusetts, were studied. Of the 50 tested, 44 had hemophilia A, and 6 had hemophilia B. Ali hemophilia A patients had moderate to severe hemophilia and received home infusions of commercial clotting factor VIII concentrate. At serum collection, | had clinical AIDS and 49 were asymptomatic. Two of the 49 developed AIDS within 3 to 6 months after the beginning of the study, making a total of three patients with AIDS in the sample. A control group of 29 healthy laboratory workers was also tested. 2C-Kit-21 Policy Keys: 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3), 3) Blood Product Safety: Inactivation of Virus (VB3) Author(s): Title: Source: Institution: Findings: Method: Chamberland, Mary E., MD, MPH; Castro, Kenneth G., MD; Haverkos, Harry W., MD; Miller, Bess [., MD; Thomas, Pauline A., MD; Reiss, Rebecca, MS; Walker, Juliette, MS; Spira, Thomas J., MD; Jaffe, Harold W., MD; Curran, James W., MD, MPH. Acquired Immunodeficiency Syndrome in the United States: An Analysis of Cases Outside High-Incidence Groups. Annals of Internal Medicine, November 1984, Vol. 101, No. 5: 617-623. Division of Field Services, Epidemiology Program Office, and AIDS Activity, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; New York City Department of Health, New York, New York. Two hundred and one cases of AIDS were reported to the Centers for Disease Control (CDC) from | June 1981 through January 1984 that could not be classified into any group identified to be at risk for this syndrome. Noncharacteristic patients were more likely to be female and less likely to be white than characteristic patients and were less likely to live in states other then New York, New Jersey, and Florida. Of the noncharacteristic patients, 25% were 50 years old or older, compared with 9% of the characteristic patients. Thirty-five had received transfusions of single-donor blood components in the 5 years preceding diagnosis of the syndrome, and 30 were sexual partners of persons belonging to a high-risk group. Information was incomplete for most remaining patients, but many of these patients were demographically similar to populations recognized to be at increased risk for AIDS; previously identified risk factors may have been present but not reported for some of them. Also, a few persons who met the case definition for AIDS probably had opportunistic disease for other reasons and did not have AIDS. The slow emergence of AIDS in new populations is consistent with transmission through sexual contact or parenteral exposure to blood. This paper describes the demographic and epidemiologic features of the first 201 cases of AIDS reported in the U.S. that could not be categorized into the groups identified by the CDC that are at most risk for AIDS: homosexual and bisexual men, intravenous drug users, hemophiliacs, and Haiti-born residents of the U.S. Data were presented for comparison with characteristic patients with AIDS. Persons less than 15 years of age are not included. When possible, living patients were interviewed by doctors or public health advisors affiliated with the CDC or local health departments. Questionnaires were used to obtain information about sociodemographic characteristics, medical history, family history, sexual practices, drug use, and occupational history. Six patients were not given questionnaires. For some patients, physicians, family members, or sexual contacts were interviewed to obtain supplemental information, especially if patients had died or were critically ill. 2C~Cha-22 Sample Size: Policy Keys: Two hundred and one AIDS patients who could not be classified into one of the characteristic AIDS risk groups are referred to as noncharacteristic cases. The 201 noncharacteristic patients differed from characteristic patients in sex, race, residence, and disease distribution. Data for 3,137 characteristic patients with AIDS reported to the CDC are presented for comparison. 1) Transmission: Blood Transfusion (IIC), 2) Transmission: Sexual Activity (IIA), 3) Populations: Heterosexuals (IA6), 4) Geographic Trends: U.S. (IB) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jaffe, H.W.; Francis, D.P.; McLane, M.F.; Cabradilla, C.; Curran, J.W.; Kilbourne, B.W.; Lawrence, D.N.; Haverkos, H.W.; Spira, T.J.; Dodd, R.Y.; Gold, J.; Armstrong, D.; Ley, A.; Groopman, J.; Mullins, J.; Lee, T.H.; Essex, M. Transfusion-Associated AIDS: Serologic Evidence of Human T-Cell Leukemia Virus Infection of Donors. Science, 23 March 1984, Vol. 223: 1309-1312. Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Jaffe, Francis, Cabradilla, Curran, Kilbourne, Lawrence, Haverkos, Spira); Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts (McLane, Mullins, Lee, Essex); American Red Cross Blood Services Laboratories, Bethesda, Maryland (Dodd); Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (Gold, Armstrong, Ley); Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts (Groopman). To evaluate further the serologic relationship of human T-cell lymphotropic virus (HTLV) or a related virus to AIDS, sera from persons who donated blood to 12 patients who later developed transfusion- associated AIDS were tested. The occurrence of positive results for antibody to HTLV membrane antigens (HTLV-MA) was significantly greater among donors to the AIDS patients (9 of [17, 7.7%) than among random donors (1 of 298, 0.3%). Of 12 sets of blood donors examined, 9 sets included a donor whose serum was positive for the presence of antibodies to HTLV-MA. In six of these nine sets, the donor who tested positive was also identified as a possible source of AIDS transmission when epidemiologic and immunologic criteria were used. The high prevalence of antibodies in homosexual male donors was surprising, since these antibodies were rare in homosexual controls. For 12 patients with transfusion-associated AIDS, investigations of the patients' blood donors were completed, including interviews for risk factors, examination for physical findings suggestive of AIDS, and analysis of blood samples. An assay for antibodies to HTLV-MA was used to examine blood serum. A total of 298 randomly selected serum specimens were used as controls. Of 157 people who donated blood to the 12 patients, 117 (74.5%) were evaluated. Control specimens were collected during 1979 and 1980 in Philadelphia (100 specimens), Madison, Wisconsin (99 specimens), and Tucson, Arizona (99 specimens). Included for comparison were 81 previously tested serum samples collected in 1981 from homosexual men matched by age, race, and residence to AIDS patients and 45 samples obtained in 1982 from homosexual men in Ithaca, New York. 1) Transmission: Blood Transfusion (IIC), 2) Populations: Blood Donors (IA7) 2C-Jaf-23 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Gascon, Pedro, MD, PhD; Zoumbos, Nicholas C., MD, PhD; Young, Neal S., MD. Immunologic Abnormalities in Patients Receiving Multiple Blood Transfusions. Annals of Internal Medicine, February 1984, Vol. 100, No. 2: 173-177. Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Immunologic testing was done for patients receiving multiple blood transfusions. Natural killer cell function was depressed in these patients, but helper/suppressor T-cell ratios were normal. Virtually all of these patients showed evidence of chronic viral infection and immunologic activation. The results show that chronic exposure to foreign antigens may be associated with immunologic abnormalities, but that frequently transfused patients do not have the same immunologic profile as reported for some homosexuals and hemophiliacs. This was a case-control study of multiply-transfused patients with testing for immunologic function. The T-cell subpopulations were quantitated by direct immunofluorescence with OKT3, OKT4, and OKT8& monoclonal antibodies. Natural killer cell activity and human interferon levels were assayed as well. Cases studied included 32 with sickle cell disease, 29 with beta- thalassemia (an inherited disorder in which the production of the beta- chain component of hemoglobin is depressed), and 12 with other anemias. Six hemophilia patients also contributed samples. Fifty normal laboratory personnel served as controls. 1) Transmission: Blood Transfusion and Blood Products (IC), 2) Cofactors: Immunological Abnormalities (IC3), 3) Immunological Aspects (IIE) 2C-Gas=-24 Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Curran, James W., MD; Lawrence, Dale N., MD; Jaffe, Harold, MD; Kaplan, Jonathan E., MD; Zyla, Lawrence, D., MPH; Chamberland, Mary, MD; Weinstein, Robert, MD; Lui, Kung-Jong, PhD; Schonberger, Lawrence B., MD; Spira, Thomas J., MD; Alexander, W. James, MD; Swinger, Gary, DVM; Ammann, Arthur, MD; Solomon, Steven, MD; Auerbach, David, MD; Mildvan, Donna, MD; Stoneburner, Rand, MD; Jason, Janine M., MD; Haverkos, Harry W., MD; and Evatt, Bruce L., MD. Acquired Immunodeficiency Syndrome (AIDS) Associated with Trans- fusions. The New England Journal of Medicine, 12 January 1984, Vol. 310, No. 2: 69-75. AIDS Program, Centers for Disease Control, Atlanta, Georgia (Curran); Department of Internal Medicine, Michael Reese Hospital, Chicago, [llinois; New York City Department of Health, New York; Beth Israel Medical Center, New York; Tennessee Department of Public Health, Nashville; Jefferson County (Alabama) Department of Public Health, Birmingham; University of California-San Francisco Medical Center, San Francisco. It was found that 18 (28%) of 64 AIDS patients without previously known risk factors had received transfusions of blood components in the 5 years before the onset of illness. These patients were significantly more likely to be white and older than other AIDS patients with no known risk factor. All of these 18 AIDS patients had Pneumocystis carinii pneumonia. They had received blood from 2 to 48 (median, 14) donors 15 to 57 (median, 27.5) months before being diagnosed with AIDS. At least one high-risk donor was identified in each case in which investigation could be completed; five of the six identified high-risk donors had low helper/suppressor T-cell ratios, and four had lymphadenopathy. The authors suggest that these findings strengthen evidence that AIDS may be transmitted in blood. Medical and social histories were obtained for all 64 AIDS patients not known to have been at risk, including detailed information on receipt of blood transfusion or blood products in the 5 years preceding the onset of illness. Persons who had donated blood to these patients were contacted for a confidential interview and a physical exam to obtain blood samples for T-cell subset analysis and other immunological studies. Donors whose samples were found to be abnormal were retested. Characteristics of patients with transfusion-associated AIDS were compared with those of others without known risk factors who had P. carinii pneumonia Sixty-four (3%) of the 2,157 AIDS cases reported to the Centers for Disease Control by 22 August 1983 who had no recognized risk factor for AIDS were tested. A subset of 18 (28%) of these 64 are included in this study because they had received blood transfusions in the five years before the onset of illness. 1) Transmission: Blood Transfusion (IIC), 2) Incubation Period (IIIC) 2C-Cur-25 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jason, J.M.; Evatt, B.L.; Chorba, T.L.; Ramsey, R.B. Acquired Immunodeficiency Syndrome (AIDS) in Hemophiliacs. Scandinavian Journal of Haematology, 1984, Suppl. 40, Vol. 33: 349-356. Division of Host Factors, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. This report summarizes the epidemiologic findings in reported cases of AIDS in hemophiliacs through September 1983. The mortality rate for the 23 hemophiliac AIDS cases was 70% within the study's time frame. Only 2 of the 23 had other known risk factors for AIDS. Most of the U.S. victims did not reside in high-risk areas. All patients had received clotting-factor concentrate, and often other blood products as well, in the 5 years prior to AIDS diagnosis. Hemophiliac AIDS patients resembled transfusion-associated and intravenous drug abuse AIDS patients and differed from homosexuals with AIDS in regard to associated diagnoses. The evidence points to the possibility that AIDS is caused by an agent transmissable through blood products. Thus, there is a need for blood-related AIDS precautions. Case reports on U.S. hemophiliacs with AIDS were obtained through the Centers for Disease Control's (CDC) AIDS surveillance system, interviews with attending physicians, reviews of reports of suspected AIDS in hemophiliacs, and review of requests to the CDC for pentamidine isethionate to treat Pneumocystis carinii pneumonia. Clinical information, demographic data, and laboratory data were obtained, and blood tests were performed to assess immune system function. Twenty-three hemophiliacs were documented as having AIDS between 1 January 1982 and 6 October 1983; 18 in the U.S., 4 in Europe (Spain and Wales), and | in Canada. Twenty-two had hemophilia A, and one had hemophilia B. Their ages ranged from 9 to 74 years (median, 35). Twenty-one were white, and two were black. 1) Transmission: Blood Products (IIC), 2) Populations: Hemophiliacs (IA3) 2C-Jas-26 [I. Transmission Modes D. Perinatal Author(s): Title: Source: Institution: Findings: Method: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Recommendations for Assisting in the Prevention of Perinatal Transmission of Human T-Lymphotropic Virus Type IlI/Lymphadeno- pathy-Associated Virus and Acquired Immunodeficiency Syndrome. Morbidity and Mortality Weekly Report, 6 December 1985, Vol. 34, No. 48: 721-732. Centers for Disease Control, Atlanta, Georgia. Recommendations are presented that are intended to assist health care providers and health departments in developing procedures to prevent perinatal (before, during, or after birth) transmission of human T-cell lymphotropic virus type III (HTLV-II). As of | December 1985, 217 (1%) of all AIDS cases identified occurred among children under 13 years of age; 60% of these children have died. These 217 cases represent only the more severe manifestations of HTLV- [ll infection; cases of AIDS-related complex (ARC) are not reported to the Centers for Disease Control (CDC), and a number of infected children may be asymptomatic as well. Of the 217 known cases, 165 (76%) have as their only risk factor a mother belonging to a high-risk group. An additional 18% were exposed to transfusions of blood or blood products; risk information is missing on the remaining 6%. Of the 217, 48% had mothers who were intravenous (I.V.) drug abusers, 17% had mothers who were born in Haiti, and 10% had mothers who were sex partners of either [.V. drug abusers or bisexual men. Forty-five percent of these patients resided in New York City, and Florida and New Jersey accounted for an additional 32%. HTLV-III is believed to be transmitted to fetuses or offspring of infected mothers during pregnancy, during labor and delivery, or shortly after birth. Transmission after birth has been implicated in at least one case in a child born to a mother who acquired the virus during a postpartum blood transfusion. HTLV-III has been isolated from the breast milk of infected women as well. The risk that infected mothers may transmit HTLV-III to their offspring and the risk of illness among pregnant women are discussed. It is not known whether pregnancy increases a woman's susceptibility to HTLV-II, but at least one study suggests that this is the case. Perinatal infection of offspring is not inevitable, however; of three children born to women who became infected by artificial insemination with semen from an infected donor, all were in good health more than | year after birth. Other instances of children born to infected women demonstrate that some children do not acquire HTLV-III from their mothers. Public health recommendations are also presented. This report presents surveillance data and a review of pediatric AIDS patients who acquired AIDS from their mothers in the perinatal period, 2D-Cen-1 Sample Size: Policy Keys: mechanisms of perinatal transmission, risk of perinatal transmission from infected mothers, and risk of illness among infected pregnant women. The information and recommendations presented in this report were developed and compiled by CDC and the U.S. Public Health Service in consultation with individuals representing a wide spectrum of agencies and organizations in the U.S. Cases of AIDS in children under 13 years of age (total, 217) reported to CDC as of | December 1985 were examined. 1) Transmission: Perinatal (IID), 2) Populations: Pediatric Cases (IA4), 3) Transmission: Blood Transfusions (IIC), 4) Transmission: Sexual Activity (IIA), 5) Geographic Trends: U.S. (IBl), 6) Cofactors: Pregnancy (IC3), 7) Transmission: Breast Milk, Artificial Insemination (IIG), 8) Other Characteristics of Disease: HTLV-III in Breast Milk (IIIF) Author(s): Title: Source: Institution: Findings: Method: Kaplan, Mark H.; Pahwa, Savita G.; Popovic, Mikulas; Sarngadharan, M.G.; Gallo, Robert C. A Classification of HTLV-II Infection Based on 75 Cases Seen in a Suburban Community. Cancer Research, September 1985, Vol. 45 (Suppl.): 4655s-4658s. Department of Medicine, Division of Infectious Diseases and Immunology (Kaplan), and Department of Pediatrics (Pahwa), North Shore University Hospital, Manhasset, New York; Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Popovic, Gallo); Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland (Sarngadharan). Patients infected with human T-cell lymphotropic virus type III (HTLV- [[I) were seen in a suburban hospital and studied for their clinical manifestations of infection, infection in their families and sexual partners, and progression of disease. Patients were classified by their clinical presentation into groups 0 to 6. Groups 0 to 3 all showed antibody to the p41 HTLV-III protein. Group 0 (9 patients) had no evident disease, Group | (16 patients) had lymphadenopathy with or without exaggerated infection, Group 2 (7 patients) had persistent lymphadenopathy with chronic hepatitis B surface antigenemia or profound hypergammaglobulinemia, and Group 3 (7 patients) had oral candidiasis with or without lymphadenopathy. Group 4 included 26 adults and 6 children with AIDS. Group 5 was a special classification for immunocompromised patients with antibody to p41 who also had underlying tumors requiring chemotherapy, and opportunistic infection. Patients in group 6 had lymphomas and antibody to p41 HTLV- III protein. (Numbers of cases are not specified for groups 5 and 6.) Four patients in group 4 developed group 6 disorders. HTLV-III infection spread in families (8 of 36 family members), all from infected mothers to their children. Of 17 sexual partners of patients, 6 were infected. Five of these six infected partners were homosexuals. An unusual number of the AIDS cases were due to blood transfusion (4 of 29), as was | of 46 other HTLV-III disorders. Two infants also presented with severe intracranial defects. The authors suggest a classification scheme for studying the clinical manifestations of HTLV-II infection; they believe the incidence of HTLV-II infection is grossly underestimated. This study consisted of case reports and clinical and epidemiologic studies of contacts of a group of patients seen at North Shore University Hospital in suburban New York City. All AIDS patients and those with generalized lymphadenopathy were monitored, as well as patients known to be in identified risk groups. Blood sera were tested for HTLV-II antibody by Western blot, and T-cell subpopulations were identified by indirect immunofluorescence with OKT3, OKT4, OKT8, and OKTII monoclonal antibodies to determine immune status. 2D-Kap-2 Sample Size: A group of 75 HTLV-III-infected patients seen in a suburban New York City hospital were studied. Patients were divided into nine groups and subgroups by type and level of HTLV-III-defined illness. Policy Keys: 1) Transmission: Perinatal, Sexual Activity, Blood Transfusion (IID,A,C) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Scott, Gwendolyn B., MD; Fischl, Margaret A., MD; Klimas, Nancy, MD; Fletcher, Mary Ann, PhD; Dickinson, Gordon M., MD; Levine, Robert S., MD; Parks, Wade P., PhD, MD. Mothers of Infants with the Acquired Immunodeficiency Syndrome: Evidence for Both Symptomatic and Asymptomatic Carriers. Journal of the American Medical Association, 18 January 1985, Vol. 253, No. 3: 363-366. Departments of Pediatrics (Scott, Levine, Parks), Medicine (Fischl, Klimas, Fletcher, Dickinson), Microbiology and Immunology (Fletcher, Parks), and Epidemiology (Levine), Division of Immunology and Infectious Diseases, University of Miami School of Medicine, Miami, Florida. Sixteen mothers of 22 infants with AIDS were followed up for evidence of clinical and immunologic abnormalities. With one exception, all mothers were clinically well at delivery but had evidence of immune system dysfunction during the study, with T-cell abnormalities. During the 30-month follow-up period, AIDS developed in five of the mothers and AIDS-related complex (ARC) in seven. Subsequent pregnancies in 11 mothers produced four affected infants, suggesting that mothers can be persistently infected. Six mothers delivered subsequent infants who remained unaffected by AIDS. The authors suggest that the mothers were the likely source of infection in their infants, that they have persistent immunologic abnormalities, and that they are at risk of developing AIDS or ARC. This study consists of case reports and prospective study of mothers of AIDS cases and their subsequent children. The mothers and their infants were followed up with repeated physical examinations and immunologic studies every 3 to 6 months between November 1982 and May 1984. Each new sibling born after an AIDS index case was also examined, studied immunologically, and followed up prospectively. Sixteen mothers of 22 affected infants were studied. Fourteen of the infants met the Centers for Disease Control criteria for AIDS in infants, while the remaining eight had ARC, defined as clinical and immunologic characteristics similar to those of the infants with AIDS but without opportunistic infection or Kaposi's sarcoma. Twelve subsequent infants of the same mothers were also studied. Twelve of the mothers were Haitians, two were American blacks, and two were white. Ages ranged from 18 to 42 years (mean, 28). 1) Transmission: Perinatal (IID), 2) Populations: Pediatric Cases (IA4) 2D-Sco-3 Author(s): Title: Source: Institution: Findings: Method: Cowan, Morton J., MD; Hellmann, David, MD; Chudwin, David, MD; Wara, Diane W., MD; Chang, R.S., MD, DSc; Ammann, Arthur J., MD. Maternal Transmission of Acquired Immune Deficiency Syndrome. Pediatrics, March 1984, Vol. 73, No. 3: 382-386. Departments of Pediatrics and Medicine, University of California, San Francisco; and Department of Medical Microbiology, University of California, Davis. Three female half-siblings, all daughters (by different fathers) of a drug- abusing prostitute with AIDS, were all found to have clinical and laboratory evidence of AIDS. All three had chronic Candida infection; two had diffuse lymph node swelling and chronic active Epstein-Barr virus (EBV) infection. Two children had died, both of Pneumocystis carinii pneumonia. Case | was born with heart and lung problems, including a heart defect, and with cytomegalovirus infection. She required numerous blood transfusions, at 23 months she showed signs of EBV infection, and she had two bouts with pneumonia during her first year. She died at age 4 of P. carinii pneumonia. Case 2 was born with jaundice, but she received no blood products in infancy. She began to have recurrent respiratory tract infections at 8 months of age and was hospitalized for same at 14 months. She also showed signs of EBV infection. She had been hospitalized for otitis media and pneumonia several times between the ages of 15 months and 3 years, but survived to the date of receipt for publication (3 years, 8 months). Case 3, the product of a 35-week pregnancy, was delivered by cesarean section and appeared well, but developed an upper respiratory tract infection at 2 months and Candida infection in the mouth and vaginal area. At 5 months she showed enlargement of both liver and spleen. At 6 months she was hospitalized with P. carinii pneumonia, of which she died. Case 4, the mother of the three girls, was a white 29-year-old resident of San Francisco who began using [.V. drugs at age 20, became a heroin addict, often shared needles, and became a prostitute at age 23, with an estimated 1,500 sexual contacts (many with bisexual men) per year for 4 years, reduced to 200 contacts per year after she was 27 years old. She had gonorrhea, swollen lymph nodes, and an enlarged spleen and was alive at the time of receipt of this article for publication. The authors suspect that all three children had an acquired immunodeficiency disease similar to AIDS. They think it most likely that the children acquired this condition from the mother shortly before or after birth. They consider case 3's cesarean delivery and subsequent development of AIDS to be evidence of transmission of an infectious agent across the placenta. Clinical histories were recorded for each of the four cases. Percentages and numbers of T cells among lymphocytes were determined. These and other tests all used standard, accepted techniques. 2D-Cow-4 Sample Size: A San Francisco prostitute who was a drug addict with AIDS and her three daughters were studied; the three daughters all had different fathers. Policy Keys: 1) Transmission: Maternal (IID), 2) Populations: Pediatric Cases (IA4), 3) Incubation Period (Pediatric Cases) (IIIC) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Scott, Gwendolyn B., MD; Buck, Billy E., MD; Leterman, Joni G., MD; Bloom, Frederick L., MD; Parks, Wade P., PhD, MD. Acquired Immunodeficiency Syndrome in Infants. The New England Journal of Medicine, 12 January 1984, Vol. 310, No. 2: 76-81. Division of Allergy, Immunology, and Infectious Diseases, Department of Pediatrics, Department of Microbiology and Immunology, and Department of Pathology, University of Miami School of Medicine, Miami, Florida. Fourteen Miami infants with clinical and laboratory features of AIDS were studied. Patients were predominantly of Haitian parentage, although two cases occurred in children of non-Haitian intravenous drug abusers. One patient had received a blood transfusion prior to developing clinical manifestations of AIDS. The predominant clinical findings included severe failure to thrive, persistent candidiasis, chronic lung infection, lymphadenopathy, and diarrhea. [Immunologic studies showed that most of the infants had lowered helper/suppressor T-cell ratios. Lymphopenia (decrease in white blood cells) was not common, although it is in adult AIDS patients. Bacterial infections were common, and bacterial sepsis (poisoning) was the major cause of death in the seven infants who died by the time of this report. At autopsy, two infants were found to have Kaposi's sarcoma. The authors suggest that these findings indicate the likelihood of trans- mission of the AIDS infectious agent from mother to child during pregnancy, at birth, or after birth. This study consists of case reports of infants diagnosed with AIDS in Miami, including clinical and blood test data. Fourteen infants (eight girls, six boys) with clinical and laboratory features of AIDS were identified in Miami, Florida from November 1980 to July 1983 and admitted to Jackson Memorial Hospital. 1) Transmission: Perinatal (IID), 2) Populations: Pediatric Cases (IA4) 2D-Sco-5 II. Transmission Modes E. Health Care Accidents Author(s): Title: Source: Institution: Findings: Mann, Jonathan M., MD, MPH; Francis, Henry, MD; Quinn, Thomas C., MD; Bila, Kapita, MD; Asila, Pangu Kaza, MD, MPH; Bosenge, Ngaly, MD; Nzilambi, Nzila, MD; Jansegers, Leopold, MD; Piot, Peter, MD; Ruti, Kalisa, MD; Curran, James W., MD, MPH. HIV Seroprevalence Among Hospital Workers in Kinshasa, Zaire: Lack of Association with Occupational Exposure. Journal of the American Medical Association, 12 December 1986, Vol. 256, No. 22: 3099-3102. Project SIDA, Ministry of Health, Kinshasa, Zaire (Mann, Francis, Bosenge, Nzilambi); AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Mann, Curran); National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (Francis, Quinn); Mama Yemo Hospital, Kinshasa, Zaire (Bila, Jansegers); Ministry of Health, Kinshasa, Zaire (Asila, Ruti); Institute of Tropical Medicine, Antwerp, Belgium (Piot). Personnel at Mama Yemo Hospital in Kinshasa, Zaire, were tested for antibody to human immunodeficiency virus (HIV) to determine whether seroprevalence was related to occupational exposure to patients and their blood. Of the 2,384 personnel tested, 152 (6.4%) were found to be seropositive. Prevalence was higher among women than among men (8.1% versus 5.2%). Workers most likely to be seropositive were relatively young, unmarried (both of these may be indirect measures of sexual behavior), had had a blood transfusion or hospitalization during the previous 10 years, and had received medical injections during the previous 3 years. Medical, administrative, and manual workers had similar rates of seropositivity, and seropositivity was not associated with any measure of patient, blood, or needle contact. This lack of association is significant in view of the fact that hospitals in developing countries have fewer injection control resources than hospitals in the United States and Europe. For instance, gloves, gowns, masks, disinfectants, and hand-washing facilities are not routinely available; needles and syringes are nearly always reused, so injection equipment is nearly always washed by hand before sterilization; and since late 1983 approximately 750 AIDS patients have been hospitalized annually at Mama Yemo Hospital. While all seropositive staff members in this study were able to work, 15% had physical findings or symptoms such as lymphadenopathy. Whether HIV infection occurred as a result of medical care procedures or whether medical care was sought as a result of previous HIV infection cannot be determined. The authors conclude that occupational risks of HIV infection are low even in developing countries. This finding is consistent with American and European studies which have demonstrated low occupational HIV transmission to health care workers. The authors suggest that infection control measures aimed at preventing hepatitis B virus, HIV, and other infections should be promoted in developing countries, rather than focusing on identification and special handling of HIV-infected patients. 2E-Man-1 Method: Sample Size: Policy Keys: The seroprevalence study was timed to coincide with a medical examination offered by the hospital's employee health unit. The interview questionnaire collected demographic data and information about potential occupational and nonoccupational risk factors for HIV exposure. Questions about sexual partners or practices were omitted to make the study acceptable in this specific hospital context. Information about age, sex, and marital status, however, may serve as indirect measures of sexual behavior. Serum samples from all subjects were tested for antibody to HIV by enzyme-linked immunoassay (ELISA). Half of the sera positive by ELISA were confirmed by Western blot; the confirmation rate was 97%. From 15 through 25 October 1984, 2,384 of the 2,492 employees at Mama Yemo Hospital in Kinshasa, Zaire, completed the study. Almost all were Zairian citizens and had lived in Kinshasa a median of 19 years. Their mean age was 36.7 years; 61% were men and 39% women. Medical workers constituted 66% of the employees, administrative 21%, and manual workers 13%. Overall, staff had worked in their present occupation at Mama Yemo for a median of 8 years, and 30% had previously worked in another medical setting. 1) Transmission: Health Care Accidents (IIE), 2) Geographic Trends: Africa (Zaire) (IB5), 3) Other Transmission: Medical Care in Developing African Countries (IIG) Author(s): Title: Source: Institutions Findings: Methods: Sample Size: Policy Keys: Henderson, David K., MD; Saah, Alfred J., MD, MPH; Zak, Barbara IJ., BSN; Kaslow, Richard A., MD, MPH: Lane, H. Clifford, MD; Folks, Thomas, PhD; Blackwelder, William C., PhD; Schmitt, James, MD; LaCamera, Deborah J., BSN; Masur, Henry, MD; Fauci, Anthony S., MD. Risk of Nosocomial Infection with Human T-Cell Lymphotropic Virus Type IlI/Lymphadenopathy-Associated Virus in a Large Cohort of Intensively Exposed Health Care Workers Annals of Internal Medicine, May 1986, Vol. 104, No. 5: 644-647. Hospital Epidemiology Service and Critical Care Medicine Service, Clinical Center; Laboratory of Clinical Investigation, Laboratory of Immunoregulation, Office of the Director, and Epidemiology and Biometry Section, Microbiology and Infectious Disease Program, National Institute of Allergy and Infectious Disease; Occupational Medical Service, Office of Research Services, Office of the Director, National Institutes of Health, Bethesda, Maryland. A group of 531 health care workers was studied prospectively; 150 of these employees reported percutaneous or mucous membrane exposure to blood or body fluids from AIDS patients in 1981. None of the 150 exposed employees had evidence of human T-cell lymphotropic virus type III (HTLV-II) infection on follow-up from 6 to 46 months following expo- sure. Of the 53l employees, 3 had evidence of HTLV-III infection; all were positive when they entered the study and none reported work- associated exposure. All three acknowledged membership in a high-risk group. This study provides strong evidence that the risk of transmission of HTLV-III in the hospital is extremely low. This prospective study of health care workers, including a subgroup who were exposed to AIDS from their patients, involved a questionnaire repeated every 6 months covering demographic characteristics, job descriptions, and type and frequency of procedures done on AIDS patients. Blood samples collected on each occasion were tested for HTLV-III antibody by enzyme-linked immunosorbent assay, with positive or borderline results confirmed by Western blot. Other blood tests for lymphocyte subsets and immunologic function were done. A group of 531 health care workers in the Clinical Center of the National Institutes of Health was studied, 150 of whom reported exposure to blood or body fluids from AIDS patients (40 with needlestick exposures and 110 with mucuous membrane exposures). Positive controls were 30 AIDS patients, and negative controls were 16 healthy heterosexuals. 1) Transmission: Health Care Accidents (IIE), 2) Populations: Health Care Workers (IA7) 2E-Hen-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: McCray, Eugene, MD; The Cooperative Needlestick Surveillance Group. Occupational Risk of the Acquired Immunodeficiency Syndrome Among Health Care Workers. The New England Journal of Medicine, 24 April 1986, Vol. 314, No. 17: 1127-1132. Epidemiology Branch, Hospital Infections Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. In this ongoing surveillance effort, a nationwide prospective study is being conducted of health care workers with documented parenteral or mucous membrane exposure to body fluids of AIDS patients. By 31 December 1985, 938 health care workers were being followed up in the surveillance project. The average length of follow-up was 15 months at this point, and 531 people had been studied for more than 1 year. Needlestick injuries and cuts with sharp instruments accounted for 76% of the exposures. Over 85% of all exposures were to blood or serum, as opposed to other body fluids. None of the health care workers had clinical signs or symptoms of AIDS at the time of this report. Analysis of helper/suppressor T-cell ratios were done for 341 (36%), and tests for human T-cell lymphotropic virus type III (HTLV-II) antibodies were done for 451 (48%). Seven health care workers who had low T-cell ratios were retested, and only three had persistently low ratios. Only 2 of 451 health care workers tested had HTLV-II antibodies. One of these two cases, a nurse with documented parenteral exposure, also had a sexual partner who was positive for HTLV-III, thus sexual transmission cannot be ruled out. This study suggests that the risk to health care workers of infection with HTLV-II through exposure to AIDS patients is low and appears to be mainly related to parenteral exposure to blood. This was a prospective surveillance study, with immunologic testing of HTLV-Ill-exposed health care workers. Exposed workers received the following evaluations upon enrollment and at each follow-up visit (every 6 months): clinical history, physical exam, and laboratory blood tests -- white-cell count with differential, platelet count, HTLV-II antibody by enzyme-linked immunosorbent assay with positive results confirmed by Western blot technique, and T-cell subpopulation quantitated by indirect immunofluorescence with monoclonal antibodies (OKT3, OKT4, and OKT8). Upon enrollment, each health care worker completed a questionnaire about nonoccupational risk factors for AIDS. This report presents surveillance results for health care workers enrolled from 15 August 1983 to 31 December 1985. A total of 938 U.S. health care workers, exposed through the end of 1985 to HTLV-II infection from AIDS patients, largely through needlesticks and cuts with sharp instruments, were studied. Health care workers were eligible if they had been exposed to blood or other body fluids of a 2E-McC-3 patient with AIDS or an AIDS-related illness through parenteral or mucous membrane contact. Policy Keys: 1) Transmission: Health Care Accidents (IIE) Author(s): Title: Source: Institution: Findings: Methods: Sample Size: Weiss, Stanley H., MD; Saxinger, W. Carl, PhD; Rechtman, David, MD; Grieco, Michael H., MD; Nadler, Jeffrey, MD; Holman, Susan, RN, MS; Ginzburg, Harold M., MD; Groopman, Jerome E., MD; Goedert, James J., MD; Markham, Phillip D., PhD.; Gallo, Robert C., MD; Blattner, William A., MD; Landesman, Sheldon, MD. HTLV-II Infection Among Health Care Workers: Association with Needle-Stick Injuries. Journal of the American Medical Association, 18 October 1985, Vol. 254, No. 15: 2089-2093. Environmental Epidemiology Branch (Weiss, Goedert, Blattner) and Laboratory of Tumor Cell Biology (Saxinger, Markham, and Gallo), National Cancer Institute, Bethesda, Maryland; National Institute on Drug Abuse, Rockville, Maryland (Ginzburg); Downstate Medical Center, Brooklyn, New York (Rechtman, Nadler, Landesman, Holman); St Luke's- Roosevelt Hospital Center, New York (Grieco); New England Deaconess Hospital, Boston, Massachusetts (Groopman). Health care workers and clinical laboratory personnel from hospitals in high-risk communities were studied to evaluate routes of exposure to and infection with human T-cell lymphotropic virus type [II (HTLV-II). Six of 23 (26%) health care workers with recognized risk factors for AIDS had HTLV-II antibodies. Thirty-nine of 278 (14%) workers at one hospital, as well as a total of 5 from other hospitals, reported possible exposure through the skin to HTLV-III, usually needlestick injuries. Three HTL V-III-positive subjects reported possible exposure to HTLV-III via needlesticks but had no other recognized AIDS risk factors. One was a symptomatic female, and her apparent source of HTLV-III infection was two puncture wounds, without injection of blood, made by needles used on AIDS patients. HTLV-II was found in her asymptomatic, long- term male sexual partner, indicating possible female-to-male transmission. (The article does not discuss her sexual partner's risk factors or the possibility of transmission from him to her.) In the two other workers with exposure, heterosexual transmission could not be ruled out. The risk of hospital HTLV-II transmission appears to be low and to be related to exposure through the skin (e.g., by needlestick injury). HTLV-III testing in health care workers and clinical laboratory personnel was conducted by enzyme-linked immunosorbent assays for antibody to the virus, with borderline and positive results confirmed by Western blot. Subjects also completed questionnaires covering health status, demographics, known risk factors for HTLV-II exposure, and dates and modes of occupational exposure to AIDS patients and their specimens. A total of 361 health care workers and clinical laboratory personnel were studied: 239 interns, residents, and fellows from a single hospital with a large AIDS population; 39 day shift laboratory workers from the same 2E-Wei-4 hospital; and 83 attending physicians, medical students, physician assistants, nurses, and drug treatment program staff from several other institutions. Policy Keys: 1) Transmission: Health Care Accidents (IIE), 2) Populations: Health Care Workers (IA7), 3) Transmission: Heterosexual (IIA) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Update: Prospective Evaluation of Health-Care Workers Exposed via the Parenteral or Mucous-Membrane Route to Blood or Body Fluids from Patients with Acquired Immunodeficiency Syndrome--United States. Morbidity and Mortality Weekly Report, 22 February 1985, Vol. 34, No. 7: 101-103. Centers for Disease Control, Atlanta, Georgia. In August 1983 the Centers for Disease Control initiated prospective surveillance of health care workers with documented exposure to potentially infectious body fluids from patients with AIDS. As of 31 December 1984, 361 such exposures were reported. The majority of exposures occurred in direct-patient-care areas of hospitals, including intensive care units, patients' rooms, and the emergency room. Laboratories, operating rooms, and morgues were the site of other exposures. Postexposure care varied considerably. Forty- eight percent of the exposed workers received wound care only or no care at all, while 35% received immunoglobulin either alone or In combination with other treatment. Complete epidemiologic data for 226 of the patients involved in these exposures was obtained as well. Tests for antibody to human T-cell lymphotropic virus type III (HTLV-II) and immunological and other abnormalities among exposed workers have all been negative. There are as yet no confirmed cases of health care workers acquiring AIDS through direct exposure to AIDS patients' body fluids. This study was a prospective follow-up of exposed health care workers, including T-cell studies and HTLV-II antibody testing. The enrollment phase of the project, initiated in August 1983, is designed to last 3 years. A total of 361 health care workers who had been directly exposed to body fluids of AIDS patients were reported from 33 states and the District of Columbia; 208 (58%) were nurses, 66 (18%) were physicians or medical students, 31 (9%) were laboratory workers, 26 (7%) were phlebotomists, 15 (4%) were respiratory workers, and the rest had less-direct patient contact. 1) Transmission: Health Care Accidents (IIE) 2E-Cen-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Hirsch, Martin S., MD; Wormser, Gary P., MD; Schooley, Robert T., MD; Ho, David D., MD; Felsenstein, Donna, MD; Hopkins, Cyrus C., MD; Joline, Carol, RN; Duncanson, Frederick, MD; Sarngadharan, M.G., PhD; Saxinger, Carl, PhD; Gallo, Robert C., MD. Risk of Nosocomial Infection with Human T-Cell Lymphotropic Virus III (HTLV-II). The New England Journal of Medicine, 3 January 1985, Vol. 312, No. 1: 1- 4. Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, Boston; Division of Infectious Diseases, Department of Medicine, Westchester County Medical Center and New York Medical College, Valhalla, New York; Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland; Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland. This study examined the risk of infection among hospital employees after needlestick injuries or repeated exposure to specimens from AIDS patients. All 33 exposed hospital employees were found to be seronegative for human T-cell lymphotropic virus type III (HTLV-II), as were all the other at-risk hospital personnel tested, despite repeated exposure in many cases over a 3-year period. By contrast, all of the AIDS (22) and AIDS-related complex (ARC) (7) patients with whose blood these people had contact were seropositive for HTLV-III antibody. The implication is that hospital workers' risk of HTLV-II infection is substan- tially less than that of hepatitis B infection, although hospital precautions should not be relaxed. It would seem that the established precautions are adequate and that risk of transmission within hospitals is low. Serum samples were taken from hospital employees who reported needlestick or other exposure to the blood of patients with AIDS or ARC and sent to the National Cancer Institute, where they were screened by enzyme-linked immunosorbent assay--assayed twice, with absorbance readings more than three times the normal average taken as a positive indicator. Negative samples were subjected to the more sensitive Western blot technique. Eighty-five hospital employees at Massachusetts General Hospital and Westchester County (New York) Medical Center were studied who were victims of needlestick or blood exposure to blood of AIDS or ARC patients: 33 accident victims, 20 researchers, 8 pathologists, 9 endoscopists, and 15 other personnel. Of the 33 accident victims, 23 were women and 10 were men. Ages of accident victims ranged from 22 to 46 years (mean, 30 years). I) Transmission: Health Care Accidents (IIE), 2) Infection Control in Occupational Settings (VC) 2E-Hir-6 Author(s): Title: Source: Institution: Findings: Method: Sample: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Prospective Evaluation of Health-Care Workers Exposed via Parenteral or Mucous-Membrane Routes to Blood and Body Fluids of Patents with Acquired Immunodeficiency Syndrome. Morbidity and Mortality Weekly Report, 6 April 1984, Vol. 33, No. 13: 181-182. Centers for Disease Control, Atlanta, Georgia. In August 1983 the Centers for Disease Control (CDC) initiated prospective surveillance of health care workers with documented parenteral (intravenous or through the skin) or mucous membrane exposure to potentially infectious body fluids from AIDS patients. By December 1983, 51 such health care workers were enrolled in the study. None of these subjects have developed signs or symptoms of AIDS at the time of this report. All but one of these subjects has been followed for less than 12 months. Exposure occurred between April 1981 and November 1983. The majority of exposures occurred in direct patient care areas. Twenty-seven (53%) exposures occurred in patients' rooms or on wards, and 12 (24%) occurred in intensive-care units; 7 (14%) took place in laboratories, and 5 (10%) occurred in operating rooms or morgues. The types of exposure included needlestick injuries, cuts with sharp instruments, mucosal exposure, and contamination of open skin sores with potentially infective body fluids. Postexposure treatment consisted of local care only in 41%, administration of hepatitis B virus immunoglobulin with or without immunoglobulin or tetanus prophylaxis in 24%, immunoglobulin alone or with tetanus in 31%, and tetanus only in 4%. The risk of AIDS transmission to health care workers through accidental exposure as described above remains unidentified, although currently available data suggest that the risk is small. Recommended health care worker precautions have been published, and it is urged that workers become familiar with and adhere to these recommendations. This report describes a prospective study of health care workers exposed to blood or body fluids of patients with AIDS. The enrollment phase of the study, which was initiated in August 1983, is designed to last 3 years. A total of 51 exposed health care workers, including 19 (37%) from New York, 9 (18%) from Texas, 7 (14%) from Pennsylvania, 5 (10%) from New Jersey, and 11 (21%) from seven other states are described. Twenty-four (47%) of the exposed workers were nurses, nine (18%) were physicians, five (10%) were phlebotomists, three (6%) were respiratory therapists, 2E-Cen-7 and the remaining ten (20%) were workers with less direct patient contact, such as laboratory and maintenance personnel. Policy Keys: 1) Transmission: Health Care Accidents (IIE) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Rhame, Frank S., MD, and The Membership of the Association for Practitioners in Infection Control. In-Hospital Needlesticks and Other Significant Blood Exposures to Blood from Patients with Acquired Immunodeficiency Syndrome and Lymphadenopathy Syndrome. American Journal of Infection Control, April 1984, Vol. 12, No. 2: 69-75. Infection Control Program, University of Minnesota Hospitals and Clinics, and Infectious Disease Section, Department of Medicine and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota. A recent survey conducted to assess the frequency of exposure of health care personnel to the blood of AIDS patients reported a total of 200 in- hospital needlestick or other significant blood exposures, 157 to blood of AIDS patients and 43 to blood of patients with lymphadenopathy syndrome (LAS). Nineteen of the AIDS exposures and 20 of the LAS exposures occurred before July 1982. No AIDS cases have been reported as a result of these exposures, including the 39 exposures which occurred more than a year before the survey. However, prospective follow-up is necessary to provide further information about these exposures. A direct-mail survey was sent to 5,834 U.S.-based members of the Association for Practitioners in Infection Control (APIC) with a proposal to establish an APIC National Registry of Hospital Exposure to AIDS and a questionnaire. Hospital information was taken from the 1972 American Hospital Association Guide. The 1,904 responses accounted for health care personnel who are members of the APIC (33% response rate, 5,834 surveys sent), or 42% of U.S. hospitals with more than 250 beds. 1) Transmission: Health Care Accidents (IIE), 2) Populations: Health Care Personnel (IA7) 2E-Rha-8 [I. Transmission Modes F. Casual Contact Author(s): Title: Source: Institution: Findings: Method: Sample Size: Berthier, A.; Fauchet, R.; Genetet, N.; Pommereuil, M.; Chamaret, S.; Fonlupt, J.; Gueguen, M.; Ruffault, A.; Montagnier, L. Transmissibility of Human Immunodeficiency Virus in Haemophilic and Non-Haemophilic Children Living in a Private School in France. The Lancet, 13 September 1986, Vol. 2, No. 8507: 598-601. Maison a Caractere Sanitaire, Internat d'Hemophiles Rey-Leroux, La Bouexiere, France; Laboratoire d'Hematologie and Laboratoire de Virologie, Centre Hospitalier Regional, Rennes, France; Centre Regional de Transfusion Sanguine, Rennes, France; Unite d'Oncologie Virale, Institut Pasteur, Paris, France. This study investigated the transmissibility of human immunodeficiency virus (HIV) in hemophiliac and nonhemophiliac chidren living together in a boarding school in France. Six patients presented with symptoms during the study. By the end of a 3-year study period, half of the hemophiliac children but none of the nonhemophiliac children showed evidence of HIV antibody. All children had had close casual contact, some of them for several years. The first seroconversions in the hemophiliacs in the study group occurred in 1982, later than those reported in the U.S but at about the same time as those reported in Europe. Since then, seroconversion in these groups has proceeded at the same rate in both locations. The risk of infection with HIV appeared to be related both to the frequency of treatment and to the type of blood product used: seven severe hemophiliacs who received local frozen cryoprecipitates only and the six patients with anti-factor VIII inhibitor treated with autoplex (noncontaminated due to its preparation method) remained HIV antibody negative. Preexisting immunological abnormalities also appeared to be aggravated by the presence of HIV. Study findings show that the transmissibility of HIV among casual contacts is low, and the authors conclude that there is no reason to exclude HIV antibody carriers from communities. Virological and immunological data were collected for all subjects. Hemophiliac sera were examined prospectively from October 1983 through November 1985, with at least two or three serological tests done at intervals of 3 months, and retrospectively from 1980 to 1983, for evidence of HIV and other viruses to determine the time of seroconversion compared with that in nonhemophiliac children living in the school. For nonhemophiliac subjects, testing was conducted and repeated throughout the study period, 1983 through 1985. Three groups of hemophiliac patients and two groups of nonhemophiliac children were studied. Hemophilia patients included 24 children with severe hemophilia living at the school, who had received treatment with local frozen or commercial concentrates (group 1); 20 home-treated severe hemophiliacs, including adults (group 2); and 15 moderately hemophiliac children living with their families and rarely or never 2F-Ber-1 transfused (group 3). Nonhemophiliac subjects included 70 children living at the school with hemophiliacs and 20 healthy children living with their families (day students), selected as pediatric controls. Policy Keys: 1) Transmission: Casual Contact (IIF), 2) Populations: Hemophiliacs (IA3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Mann, Jonathan M., MD, MPH; Quinn, Thomas C., MD; Francis, Henry, MD; Nzilambi, Nzila, MD; Bosenge, Ngaly, MD; Bila, Kapita, MD; McCormick, Joseph B., MD; Ruti, Kalisa, MD; Asila, Pangu Kaza, MD, MPH; Curran, James W., MD, MPH. Prevalence of HTLV-III/LAV in Household Contacts of Patients with Confirmed AIDS and Controls in Kinshasa, Zaire. Journal of the American Medical Association, 8 August 1986, Vol. 256, No. 6: 721-724. Project SIDA (Mann, Francis, Nzilambi, Bosenge), Ministry of Health (Ruti, Asila), Mama Yemo Hospital (Bila), Kinshasa, Zaire; AIDS Program (Mann, Curran) and Special Pathogens Branch, Division of Viral Diseases (McCormick), Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (Quinn, Francis). Household contacts of 46 patients with AIDS and 43 human T-cell lymphotropic virus type III (HTLV-III)-negative controls in Kinshasa, Zaire, were tested for evidence of HTLV-III infection. Twenty of 204 (9.8%) case household members and 3 of 155 (1.9%) control household members had blood tests positive for antibodies to HTLV-II. Eleven of 18 (61.1%) spouses of patients were positive, compared with | of 27 (3.7%) control spouses. Except for spouses, the rate of HTLV-II positivity did not differ significantly between case and control household members. For adults in case households who were not spouses, the number positive for HTLV-III was identical to that predicted from sex- and age-specific prevalence rates. These preliminary data support conclusions from household studies conducted in the United States and Europe and from studies of hospital workers in the United States and Africa which suggest that HTLV-II transmission other than by classic routes (i.e., sexual transmission, exposure to blood or blood products, and mother-infant transmission) occurs very rarely. This study consisted of case-control HTLV-III testing of household contacts of AIDS patients and HTLV-Ill-negative persons. The CDC definition of AIDS was modified to fit the available technology, although all such patients were repeatedly positive for antibodies to HTLV-IIIL. These results were confirmed by Western blot. Household contacts were considered positive for antibodies to HTLV-III if it was reactive on two enzyme-linked immunosorbent assays and confirmed by Western blot. All members of households were sought for interviews and blood tests. A total of 204 case household members and 155 control household members were studied. Case household contacts consisted of 18 spouses and 186 others (19 parents, 64 children, 75 siblings); the control household contacts consisted of 127 spouses and 128 others (18 parents, 49 children, 37 siblings, 14 other family, 10 nonfamily). 2F-Man-2 Policy Keys: 1) Transmission: Casual Contact (IIF), 2) Transmission: Sexual Activity (IIA), 3) Geographic Trends: Africa (Zaire) (IB5) Author(s): Title: Source: Institution: Findings: Method: Friedland, Gerald H., MD; Saltzman, Brian R., MD; Rogers, Martha F., MD; Kahl, Patricia A., RN; Lesser, Martin L., PhD; Mayers, Marguerite M., MD; Klein, Robert S., MD. Lack of Transmission of HTLV-III/LAV Infection to Household Contacts of Patients with AIDS or AIDS-Related Complex with Oral Candidiasis. The New England Journal of Medicine, 6 February 1986, Vol. 314, No. 6: 344-349, Division of Infectious Diseases, Department of Medicine, Departments of Pediatrics, Biostatistics, and Epidemiology, Montefiore Medical Center, North Central Bronx Hospital, and Albert Einstein College of Medicine, Bronx, New York; AIDS Branch, Centers for Disease Control, Atlanta, Georgia. To determine the risk of transmission of human T-cell lymphotropic virus type IlI/lymphadenopathy-associated virus (HTLV-III/LAV), nonsexual household contacts of patients with AIDS or AIDS-related complex (ARC) with oral candidiasis were studied. The contacts (68 children and 33 adults) had shared household items and facilities and had close personal interaction with the patient for a median of 22 months (range, 3 to 48) during the period of presumed infectivity. No household contact had AIDS, but one child met the criteria for ARC. Two of 101 contacts were positive for HTLV-III antibodies as tested by enzyme-linked immunosorbent assay (ELISA), but only one was positive by Western blot. The former was interpreted as a false-positive; the latter was the 5-year-old daughter of two intravenous (I.V.) drug abusers and may have contracted the infection perinatally (at birth or in utero) rather than through household contact, because she had had signs of HTLV-II infection since infancy. Immunologic testing of the household contacts gave the following results: 79 of 86 tested had normal lymphocyte counts, while the remaining 7 had low counts; 84 of 94 had normal immunoglobulin G levels, while 9 had elevated levels and | had a low level; 92 of 100 had a normal percentage of helper T cells, 6 had a low percentage, and 4 had low helper/suppressor T-cell ratios; 83 of 86 had normal absolute numbers of T cells, and 3 had low counts. Only one subject, the 5-year-old seropositive child, had more than one immu- nologic abnormality. This important study supports the view that longstanding household exposure to patients with AIDS is associated with little or no risk of transmission of HTLV-III/LAV infection. Evaluation of household contacts began in October 1984 and continued through April 1985. Household contacts were defined as persons who were not sexual partners but who lived in the same household as the AIDS index case for at least 3 months in the period starting 18 months before the onset of symptoms. Each contact was interviewed and given a physical examination and laboratory tests. The interview focused on demographic characteristics, medical history, possible risk factors for AIDS, history of sexual activity and drug use, and duration and type of 2F-Fri-3 Sample Size: Policy Keys: exposure to the AIDS patient. Physical examinations focused on the presence of lymphadenopathy, oral candidiasis, weight loss, and failure to thrive. Laboratory evaluation included complete blood count and measurement of immunoglobulins, T-cell subsets, and antibodies to HTLV-III/LAV by ELISA. A total of 101 household contacts of 39 AIDS and ARC patients constituted the study population. Of the 39 index patients, 37 had AIDS and two had ARC with oral candidiasis; 27 were male and 12 female; 28 were [.V. drug abusers; 3 were homosexual or bisexual, 1 was both; 3 were sexual partners of persons in high-risk groups; and 4 had no documented risk factor for AIDS. None of the household contacts had sexual contact with a patient with AIDS or had any other risk factors. Of the 101 household contacts, 72 were Hispanic, 18 were black, 7 were white, and 4 were in other ethnic groups. Contacts included 68 children under the age of 18 (50 were biologic children of AIDS patients, 18 were not), 3 offspring over age 18, 10 siblings, 11 parents (2 fathers and 9 mothers), and 9 other relatives. Thirty-three of the contacts were older than 18 years, 47 were 6 to 18 years old, and 21 were less than 6 years of age. 1) Transmission: Casual Contact (IIF), 2) Transmission: Perinatal (IID) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Lawrence, Dale N.; Jason, Janine M.; Bouhasin, John D.; McDougal, J. Stephen; Knutsen, Alan P.; Evatt, Bruce L.; Joist, J. Heinrich. HTLV-III/LAV Antibody Status of Spouses and Household Contacts Assisting in Home Infusion of Hemophilia Patients. Blood, September 1985, Vol. 66, No. 3: 703-705. Division of Host Factors, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; Missouri-Illinois Regional Hemophilia Comprehensive Diagnostic and Treatment Center, St. Louis, Missouri; Cardinal Glennon Children's Hospital, St. Louis, Missouri; St. Louis University Medical Center. Adult and pediatric hemophilia A and B patients and nonhemophiliac members of 28 families were studied to observe the extent of risk to infusion assistants and other household contacts of hemophiliacs. All 50 household contacts, including three spouses of human T-cell lymphotropic virus type [II (HTLV-II)-positive patients, were immunologically normal and tested negative for antibodies to HTLV-II. The average time since seroconversion among hemophiliacs was estimated at 20 months. Family members who acted as infusion assistants collectively experienced 44 person-years of exposure without becoming positive for HTLV-III antibodies. These results are interpreted to suggest that the likelihood of transmission of HTLV-II from hemophiliacs to persons assisting in their therapy is extremely low. This study involved serologic testing of hemophiliacs and their household contacts. The prevalence of seropositivity among household contacts was determined at the time of enrollment in the study; the estimated seroconversion rate among hemophiliacs and the estimated at-risk interval of exposure for infusion assistants were calculated from retrospective evaluation of sera obtained from 17 of the hemophiliacs during the August 1984 study, and 16 comparable others from whom sera had been collected, frozen, and stored between 1981 and 1984. Serum samples were tested by Western blot for antibodies to HTLV-II. T-cell subpopulations were enumerated by fluorescence with OKT3, OKT#4, and OKT8 monoclonal antibodies. Hemophiliacs were also questioned about clotting-factor use, other blood product receipt, sexual practices, any AIDS-associated illnesses or symptoms, and home therapy practices. Twenty-eight St. Louis, Missouri, area families (total, 84 persons) were enrolled in the study in August 1984, each consisting of at least one patient with hemophilia A or B who used commercial clotting-factor concentrates and at least one household contact. The sample consisted of 34 hemophiliacs and 50 household contacts (20 mothers, 8 fathers, 1 2F-Law-4 grandmother, 11 siblings, 6 spouses who were steady sexual partners for 6 months or more, and 4 children). Policy Keys: 1) Transmission: Casual Contact (IIF), 2) Transmission: Health Care Accidents (IIE), 3) Populations: Hemophiliacs (IA3) [I. Transmission Modes G. Other Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Bromwich, P.D.; Walker, A.P.; Gregson, Sue H.; Ross, Caroline F.; Eglin, R.P.; Macey, Joyce E.M. Screening for Antibodies to HTLV-II Amongst the Semen Donors of an AID Programme. British Journal of Obstetrics and Gynaecology, March 1986, Vol. 93: 279- 281. Nuffield Department of Obstetrics and Gynaecology, Public Health Laboratory, John Radcliffe Hospital, Headington, Oxford; British Pregnancy Advisory Service, Austy Manor, Wootton Wawen, West Midlands, England. Concern over the possible transmission of AIDS through artificial insemination with donor semen prompted screening of 233 semen donors for the presence of human T-cell lymphotropic virus type III (HTLV-III). Donors at particular risk for AIDS were excluded from the study. Donors were screened for the presence of hepatitis B virus surface antigens and syphilis, and no donors tested positive for either. After further testing, none of the donors had detectable antibodies to HTLV-II. Given the geo- graphic and social distribution of the donor population, the authors did not find this result surprising, but interpret the results as reassuring for recipients of donated semen. All prospective donors in this study were informed of the risk factors involved in the transmission of HTLV-II, and any who were at particular risk were excluded before further testing. Suitable donors were serologically screened for the presence of hepatitis B virus surface antigen and syphilis. Sera were tested for antibody to HTLV-II with a biotin-streptavidin-enhanced indirect immunofluorescence assay. The subjects in this study were 233 British male semen donors attending branches of the British Pregnancy Advisory Service and the Nuffield Department of Obstetrics and Gynaecology during the early part of 1985. Centers were located in Glasgow, Liverpool, Doncaster, Birmingham, Leamington Spa, Brighton, Bournemouth, and Oxford. The majority of those who became regular donors at these centers were students (74%) or unemployed (11%), mostly exstudents, with the remainder (15%) coming from a wide range of social backgrounds. 1) Transmission: Artificial Insemination (IIG) 2G-Bro-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Stewart, G.J.; Cunningham, A.L.; Driscoll, G.L.; Tyler, J.P.P.; Barr, J.Ay Gold, J.; Lamont, B.J. Transmission of Human T-Cell Lymphotropic Virus Type III (HTLV-III) by Artificial Insemination by Donor. The Lancet, 14 September 1985, Vol. 2, No. 8455: 581-584. Immunology Unit, Department of Medicine, and Departments of Obstetrics and Gynaecology and Virology, Westmead Hospital; Sydney AIDS Clinic, Sydney Hospital, Sydney, Australia. A study of eight women who received artificial insemination (AI) with frozen sperm from an asymptomatic carrier of human T-cell lymphotropic virus type III (HTLV-II) revealed that four recipients were seropositive. Of the seropositive group, one had generalized persistent lymphadenopathy, and the other three remained symptom-free 3 years after Al. The seronegative group received semen stored for an average of 12.75 months, receiving an average of l4 donations from the seropositive donor. The seropositive group received semen stored for an average of 6.8 months, also receiving an average of l4 donations from the seropositive donor. Each seropositive woman had also received semen from other donors. Of these six additional donors, five were tested and all five were seronegative. These six other donors had donated semen to 30 other women at the same clinic. Of 28 of these women tested, all were healthy and seronegative. The husbands of the four seropositive women were tested, and all were seronegative, despite regular sexual contact without condoms, up to 3 years after the Al. Three children of three seropositive recipients, all over | year old, were tested; all are in good health and are seronegative, despite the fact that their mothers contracted the virus many months before conception. This study indicates that HTLV-III can be transmitted via Al without other bodily contact. The findings confirm the role of semen in heterosexual transmission of the virus and suggest that in women with HTLV-II antibodies pregnancy and subsequent breastfeeding do not necessarily lead to infection of the infant. Sera for this laboratory study were screened for HTLV-II by enzyme- linked immunosorbent assay. Positive results were confirmed by Western blot. Circulating lymphocyte subsets were determined by using monoclonal antibodies against T4 and T8 markers and analyzed by flow cytometry. The study group included eight AI recipients of sperm from a symptomless carrier of HTLV-III, their husbands, three children of three seropositive recipients (all over | year old), five other semen donors, and 28 healthy Al recipients of their semen. 2G-Ste-2 Policy Keys: 1) Transmission: Artificial Insemination (IIG), 2) Transmission: Perinatal (IID), 3) Transmission: Sexual Activity (IIA), 4) Geographic Trends: Australia (IB3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Ziegler, John B.; Johnson, Richard O.; Cooper, David A.; Gold, Julian. Postnatal Transmission of AIDS-Associated Retrovirus From Mother to Infant. The Lancet, 20 April 1985, Vol. 1, No. 8434: 896-898. Prince of Wales Children's Hospital and St. Vincent's Hospital, Centre for Immunology, University of New South Wales; Albion Street Centre, Sydney Hospital, Sydney, Australia. The third child of a previously healthy woman was delivered by cesarean section. After delivery, the mother received a blood transfusion. One unit of blood came from a male in whom AIDS developed 13 months later. The baby was breast-fed for 6 weeks. The mother proved to have lymphadenopathy, antibody to human T-cell lymphotropic virus type [II (HTLV-III), and a reduced helper/suppressor T- cell ratio. The infant failed to thrive and had eczema from 3 months on and also had antibodies to HTLV-IIl. The infant had normal T-cell ratios, and the father and other siblings all tested negative for HTLV-III antibody. Since the mother's blood transfusion happened after the baby's birth, the infant was presumably infected via breast milk or by some other form of close contact with the mother. This study is a case report of postnatal AIDS transmission. One infant, his mother, and other family members were studied. 1) Transmission: Breast Milk (IIG), 2) Incubation Period (IIIC) 2G-Zie-3 III. Characteristics of Disease A. Diagnostic Definitions and Clinical Manifestations of AIDS 1. Kaposi's Sarcoma Author(s): Titles Source: Institution: Findings: Method: Sample Size: Policy Keys: Otu, A.A. PhD, FRCSEd. Kaposi's sarcoma and HTLV-II: a study in Nigerian adult males. Journal of the Royal Society of Medicine, September 1986, Vol. 79: 510- S514. Department of Surgery, College of Medical Sciences, University of Calabar, Nigeria. This study examines sera from 37 adult Nigerian men with Kaposi's sarcoma (KS), 30 contemporary controls with primary cell carcinoma of the liver, and 150 healthy non-tumor-bearing negative controls were tested for antibody to human T-cell lymphotropic virus type [1I/lymphadenopathy-associated virus (HTLV-III/LAV). None of the serum samples was positive for antibody to HTLV-III[/LAV. Ten of the 37 KS patients received multiple blood transfusions in the course of treatment (blood is not screened for HTLV-III/LAV in most regions of tropical Africa). Although the men were tested before and after multiple transfusions, no seroconversion occurred. The authors conclude that Nigerian KS is not associated with infection by HTLV-III/LAV and that endemic tropical African KS and epidemic AIDS-linked KS seem to be two different diseases with possibly different etiological agents. Serum samples were tested for antibody to HTLV-III/LAV by enzyme- linked immunosorbent assay in West Germany. Between January 1978 and December 1982, 37 adult male KS patients were tested. Their ages ranged from 18 to 55 years (mean, 30 years). Thirty patients, 25 male and 5 female, with histologically proven primary cell carcinoma of the liver served as the positive control group. Negative control was provided by 150 young adults who attended the University of Calabar (Nigeria) Teaching Hospital outpatient department for unrelated minor ailments. 1) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IlIAl), 2) Geographic Trends: Africa (Nigeria) (IB5) 3A1-0Otu-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Mittelman, A., MD; Wong, G., PhD; Safai, B., MD; Myskowski, P., MD; Gold, J., MD; Koziner, B., MD. Analysis of T Cell Subsets in Different Clinical Subgroups of Patients with the Acquired Immune Deficiency Syndrome: Comparison with the "Classic" Form of Kaposi's Sarcoma. The American Journal of Medicine, June 1985, Vol. 78: 951-956. Memorial Sloan-Kettering Cancer Center, New York, New York. This study was conducted to describe the range and variability of T-cell subset populations and the helper/suppressor T-cell ratio in different patient groups, including a comparison of AIDS Kaposi's sarcoma (KS) and the classic type of KS. Ninety patients were grouped according to three different forms of AIDS: KS of the recent-outbreak type (38), reactive lymphadenopathy (27), and opportunistic infections (17). A fourth group of patients had classic KS (8). All patients with classic KS had been pre- viously treated with electron-beam irradiation. These four groups were compared with a group of 40 normal control subjects. Peripheral blood mononuclear cells isolated by density separation were reacted with a panel of mouse monoclonal antibodies that recognizes all peripheral blood T cells, as well as helper and suppressor T-cell subsets. The helper /suppressor T-cell ratio was used to define the balance between these two subsets. All three groups with AIDS with or without KS showed a decrease in this ratio. The group with classic KS showed individual T-cell subset values that were also abnormal. According to these authors, these findings confirm the previously reported imbalance of T-cell subsets in patients with AIDS and KS, which is also evident in patients with treated classic KS. Peripheral blood samples were drawn from all patients and incubated overnight. By using immunofluorescent analyses, the percentage of mononuclear cells binding monoclonal antibodies was determined with commercial OKT3, OKT4, and OKT8 antibodies. The ratio of OKT4- positive to OKT8-positive cells was used to analyze the balance between helper and suppressor T-cell subpopulations. Study findings are described for each of four patient groups and their controls. Between 1981 and 1983, 82 young homosexual patients were seen at Memorial Hospital, New York City. These patients were divided into the following three categories: (1) 27 presented with only reactive lymphadenopathy that, on biopsy, was shown to be reactive hyperplasia (cell proliferation of known cause); (2) 17 patients had opportunistic infections; the infections that were observed were due to organisms such as Pneumocystis carinii, mycobacteria, cytomegalovirus, and others; and (3) 38 patients had the newly described form of KS involving not only skin but also nonskin sites. Another group of eight non-AIDS patients had the classic form of KS. All of these patients were elderly, with only skin lesions on their arms and legs, and all had been treated with electron- beam irradiation. Forty normal control subjects were chosen from a large number of anonymous donors seen at the same hospital. 3A1-Mit-2 Policy Keys: 1) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIAl), 2) Populations: Homosexuals (IA 1), 3) Immunological Aspects (IIE) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Moskowitz, Lee B., MD; Hensley, George T., MD; Gould, Edwin W., MD; Weiss, Steven D., MD. Frequency and Anatomic Distribution of Lymphadenopathic Kaposi's Sarcoma in the Acquired Immunodeficiency Syndrome: An Autopsy Series. Human Pathology, May 1985, Vol. 16, No. 5: 447-456. Department of Pathology, University of Miami School of Medicine, Miami, Florida. This study reports the autopsy findings for 52 patients who died with AIDS and Kaposi's sarcoma (KS). Nineteen of the patients had typical KS alone. Forty-nine of the patients had another, unusual variety of KS (the inflammatory variant) as well as the more typical form. The unusual variant was found in all of the risk groups studied. There appeared to be a biologic transition from the variant form of KS to the typical form in many of the cases. The most common organs involved in KS of either type were the lymph nodes and the spleen. The recognition of microscopic evidence of KS in more than 90% of patients in this autopsy series indicates that KS is more common in AIDS than has generally been appreciated. Case reports and autopsy findings from Jackson Memorial Hospital, Cedars Medical Center, and University of Miami in Florida from April 1980 to October 1983 were reviewed. Fifty-two Florida patients who had died of AIDS (by Centers for Disease Control definition) were studied, including 23 Haitians, 19 homosexual men, 5 intravenous drug abusers, 2 hemophiliacs (type A), and 3 persons (1 male, 2 female) of unknown risk. The ratio of men to women was 4.8 to 1. 1) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA1) 3A1-Mos-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Ognibene, Frederick P., MD; Steis, Ronald G., MD; Macher, Abe M., MD; Liotta, Lance, MD, PhD; Gelmann, Edward, MD; Pass, Harvey I[., MD; Lane, H. Clifford, MD; Fauci, Anthony S., MD; Parrillo, Joseph E., MD; Masur, Henry, MD; Shelhamer, James H., MD. Kaposi's Sarcoma Causing Pulmonary Infiltrates and Respiratory Failure in the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, April 1985, Vol. 102, No. 4: 471-475. Critical Care Medicine Department, Clinical Center; Medicine Branch, Laboratory of Pathology, and Surgery Branch, National Cancer Institute; and Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. This study characterized features of pulmonary dysfunction caused by Kaposi's sarcoma (KS). In 66 AIDS patients with KS studied during a 30- month period, there were 30 episodes of pulmonary dysfunction for which biopsies were done. These episodes can be divided into four groups: 6 episodes were due to pulmonary KS, 6 others were due to KS and associ- ated opportunistic infections (Ols), 13 were due to Ols only, and 5 were due to nonspecific interstitial pneumonitis. Clinical manifestations of the lung disease due to KS were not different from those of lung disease due to infections. In AIDS patients, KS is not usually life-threatening, but severe pulmonary dysfunction is one of the most common life-threatening processes. In this study, pulmonary KS did not occur only as a terminal manifesta- tion: three patients had extensive pulmonary KS early in AIDS, and five had KS with AIDS that was minimally progressing. KS may be a cause of diffuse pulmonary infiltrates. Patients responded (temporarily) to combination chemotherapy or whole-lung irradiation. It is important to diagnose KS as a cause of pulmonary dysfunction, because treating pneumonia, particularly Pneumocystis carinii pneumonia, in KS patients with trimethoprim-sulfamethoxazole or pentamidine may give slow results and often cause adverse reactions. Pulmonary KS could only be documented in large tissue sections available from open-lung biopsy or autopsy samples. In this study, a diagnosis of KS was never made by transbronchial biopsy. Results indicate that pulmonary KS cannot be reliably diagnosed without a large piece of tissue, but it is important to note that bronchoscopy was a useful tool for initial diagnosis. This clinical study analyzed lung biopsies, either transbronchial or open thoracotomy (through the chest); patient symptoms (fever, cough, dyspnea); arterial blood gas; chest x-rays; clinical course of disease; and autopsy records. Sixty-six AIDS patients with Kaposi's sarcoma seen between 1982 and 1984 at the National Institutes of Health were studied. 1) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IlIIAl), 2) Treatment: Symptom Management (IVB), 3) Diagnostic Indicators (I[IA3) 3A1-Ogn-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Bayley, A.C.; Cheingsong-Popov, R.; Dalgleish, A.G.; Downing, R.G. Tedder, R.S.; Weiss, R.A. HTLV-II Serology Distinguishes Atypical and Endemic Kaposi's Sarcoma in Africa. The Lancet, 16 February 1985, Vol. 1, No. 8425: 359-361. Department of Surgery, University Teaching Hospital, Lusaka, Zambia (Bayley); Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire (Downing); Chester Beatty Laboratories, Institute of Cancer Research, London (Cheingsong-Popov, Dalgleish, Weiss); Virology Section, Department of Microbiology, Middlesex Hospital Medical School, London, England (Tedder). Serum samples from African patients with Kaposi's sarcoma and AIDS- related disorders and from normal subjects in Uganda and Zambia were tested for antibodies to human T-cell lymphotropic virus (HTLV) types I, [I and III. Nearly 90% of patients with AIDS-related disorders or with atypical, aggressive Kaposi's sarcoma were positive for HTLV-III antibody in both countries. Only 17% of patients with classic (nonfatal, slow-spreading) Kaposi's sarcoma were positive for HTLV-II antibody. Among controls, 20% were positive in Uganda, but only 2% in Zambia. None of the subjects tested had antibodies to HTLV-I or to HTLV-II. These results are further evidence of the emergence of a clinically atypical form of Kaposi's sarcoma in Africans which resembles that seen in American patients with AIDS and is associated with HTLV-III infection. The low frequency of HTLV-II antibodies in the normal Zambian population, together with the first appearance of HTLV-III- associated diseases during the past 2 years, suggests that this virus may be new to Zambia, although it may have been present in Uganda for a longer period of time. Case-control descriptions were provided based on testing for antibodies to HTLV types [, II and III by various assays. The study included 19 patients with AIDS-related disorders, 15 from Zambia and 4 from Uganda; 30 patients with classic Kaposi's sarcoma, 13 from Uganda and 17 from Zambia, including 3 persons originating from Kenya and | from Mozambique; 26 patients with atypical Kaposi's sarcoma, 22 from Zambia, and 4 from Uganda; 158 Zambian controls (mostly newly delivered mothers); and 51 Ugandan controls. 1) Clinical Manifestations: Kaposi's Sarcoma (classic vs. AIDS-related) (IITA1), 2) Geographic Trends: Africa (Uganda, Zambia) (IB5) 3A1-Bay-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Bayley, Ann C. Aggressive Kaposi's Sarcoma in Zambia, 1983. The Lancet, 16 June 1984, Vol. 1, No. 8390: 1318-1320. Department of Surgery, University Teaching Hospital, Lusaka, Zambia. Between 1975 and 1982, 8 to 12 new cases of Kaposi's sarcoma (KS) were reported each year in Lusaka, Zambia, and the clinical presentation and tumor behavior conformed to the descriptions of endemic (i.e., non- AIDS-related) KS in Uganda and Kenya. In 1983, 23 patients presented with KS. Ten men, mean age 41, presented with typical symptoms and signs, and all 10 responded promptly to treatment. Thirteen other KS patients (10 men and 3 women), mean age 27, presented with unusual symptoms, including generalized lymph node disease; sores in the mouth, stomach, or intestines; difficulty in breathing; gross weight loss; and absence of KS patches or swellings on the limbs. Eight of these 13 atypical KS patients failed to respond to treatment and died before the end of 1983. There were no deaths among the patients with typical endemic-type KS. Case reports are presented of patients with endemic and AIDS-like cases of KS who were admitted to the University Teaching Hospital, Lusaka, Zambia, between | January 1983 and 31 December 1983. The study sample included 23 patients: 10 typical (endemic-type) male KS patients (mean age, 41 years) and 13 atypical (AIDS-like) KS patients (10 men, 3 women, age 17 to 38, with a mean age of 27 years), all from Zambia. 1) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IlIALl) 2) Geographical Trends: Africa (Zambia) (IB5) 3A1-Bay-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Patow, Carl A., MD; Steis, Ronald, MD; Longo, Dan L., MD; Reichert, Cheryl M., MD, PhD; Findlay, Peggy A., MD; Potter, Dorothy, MD; Masur, Henry, MD; Lane, H. Clifford, MD; Fauci, Anthony S., MD; Macher, Abe M., MD. Kaposi's Sarcoma of the Head and Neck in the Acquired Immune Deficiency Syndrome. Otolaryngology - Head and Neck Surgery, June 1984, Vol. 92, No. 3: 255- 260. Otolaryngology, Head and Neck Surgery, Walter Reed Army Medical Center, Washington, D.C. (Patow); Medicine Branch, Division of Cancer Treatment (Steis, Longo), Laboratory of Pathology (Reichert, Macher), Radiation Oncology Branch (Findlay); Surgery Branch (Potter), National Cancer Institute, Bethesda, Maryland; Critical Care Medicine Department, Clinical Center (Masur), and Laboratory of Immuno- regulation, National Institute of Allergy and Infectious Diseases (Lane, Fauci), National Institutes of Health, Bethesda, Maryland. To assess the clinical course and complications of Kaposi's sarcoma (KS) in AIDS cases, this study reports the cases of 13 homosexual and bisexual male AIDS patients with KS affecting the head, neck, or oral cavity. Nine of the patients had KS as the initial presentation of AIDS, with five having KS in the head or neck. KS in this group was frequently found in other parts of the body, including the lungs and gastrointestinal system. Study findings suggest that the mortality rate in this subgroup of AIDS patients is very high (62%), with an average life span of 11 months after initial diagnosis. Medical case reports with detailed clinical information from the National Institutes of Health were reviewed. Dates of case collection are not given. Summary case reports are presented. Thirteen cases of KS in eight homosexual and five bisexual men were reviewed; their ages ranged from 21 to 52 years (average, 38). Seven patients reported nonintravenous recreational drug use, while one was an intravenous drug abuser. 1) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IlIAl), 2) Incubation Period and Disease Stages (IIIC), 3) Populations: Homosexuals (IAL) 3A1-Pat-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Downing, R.G.; Eglin, R.P.; Bayley, A.C. African Kaposi's Sarcoma and AIDS. The Lancet, 3 March 1984, Vol. 1, No. 8375: 478-480. Public Health Laboratory Service, Centre for Applied Microbiology and Research, Porton Down, Salisbury (Downing); Department of Virology, Oxford Public Health Laboratory, John Radcliffe Hospital, Oxford, England (Eglin); Department of Surgery, University Teaching Hospital, Lusaka, Zambia (Bayley). Sixteen Zambian patients with Kaposi's sarcoma (KS) were studied to determine whether they had evidence of lymphopenia (decreased numbers of lymphocytes) with decreased T-cell ratios or previous infections with opportunistic pathogens. Tests for viruses commonly associated with AIDS were also performed. Twelve patients had reduced T-cell ratios, and two of these also had lymphopenia. Toxoplasma and Pneumocystis pneumonia were not more prevalent in KS patients than in controls. All 16 patients had antibodies to cytomegalovirus, 15 had antibodies to Epstein-Barr virus, and 13 had antibodies to human T-cell lymphotropic virus (HTLV). Five patients had evidence of previous infection with hepatitis B virus. African patients with KS seem to have immunologic and virus profiles similar to those of American AIDS patients. This study involved case-control testing of African KS patients and healthy African control subjects. Immunologic and virus profiles were assessed. Twenty-six Zambian nationals were included in this study; 16 KS patients and 10 controls. 1) Clinical Manifestations: Kaposi's Sarcoma (IIIAl), 2) Geographic Trends: Africa (Zambia) (IB5) 3A1-Dow-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Volberding, Paul, MD; Conant, Marcus A., MD; Stricker, Raphael B., MD; Lewis, Brian J., MD. Chemotherapy in Advanced Kaposi's Sarcoma: Implications for Current Cases in Homosexual Men. The American Journal of Medicine, April 1983, Vol. 74, No. 4: 652-656. Department of Medicine, San Francisco General Hospital and Cancer Research Institute; Department of Dermatology, University of California, San Francisco, California. This report reviews the relatively new appearance of Kaposi's sarcoma (KS) in young, male homosexuals in several major urban areas of the U.S. (New York, Los Angeles, and San Francisco). These men have a type of KS commonly found in elderly men of Italian or Jewish origin and in black African males. [ts appearance has been associated with immunocompromise, lymphoma, and leukemia, and its histological features have suggested an important interrelationship with the immune system. Because of its geographical distribution in Africa, KS may have a viral association, supported by seroepidemiological evidence. Important epidemiological evidence for the U.S. includes a history of multiple sex partners, previous sexually transmitted diseases, multiple viral infections, and the use of a variety of recreational drugs, including inhaled nitrites. A linkage of KS with immune dysfunction is postulated. Associated immunological abnormalities have included cutaneous anergy (diminished skin sensitivity to certain allergy proteins), reduction in total lymphocytes, reversal of the normal ratio of helper and suppressor T cells, and deficient natural killer cell activity. Clinical impressions to date suggest that the "standard" conservative therapy for KS is not appropriate for the current cases, which frequently involves a systemic and rapidly progressive illness in a host already weakened by concomitant disease. In early reports of current cases of KS in homosexual men, therapy modes differed. The authors suggest that because the frequent underlying immunodeficiencies must be taken into consideration, trials will have to be appropriately aggressive but as immune system-sparing as possible. This was a comparative study using information derived from a study by Templeton and Bhana (National Cancer Institute, 1975) on treatment of KS in Africa and information compiled by investigators from several institutions in collaboration with the Centers for Disease Control and the National Cancer Institute in an attempt to standardize treatment for this new population of KS patients. Not applicable. 3A1-Vol-9 Policy Keys: 1) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIAL), 2) Cofactors: Demographic Status (IC1), 3) Geographic Trends: U.S. (IBl), 4) Populations: Homosexuals (IA1), 5) Immunological Aspects (IIIE), 6) Treatment: Symptom Management (IVB) [II. Characteristics of Disease A. Diagnostic Definitions and Clinical Manifestations of AIDS 2. Opportunistic Infections Author(s): Title: Source: Institution: Findings: Blanche, S., MD; Le Deist, F., MD; Fischer, A., MD; Veber, F., MD; Debre, M., MD; Chamaret, S., MTS; Montagnier, L., MD; Griscelli, C., MD. Longitudinal Study of 18 Children with Perinatal LAV/HTLV-III Infection: Attempt at Prognostic Evaluation. The Journal of Pediatrics, December 1986, Vol. 109, No. 6: 965-970. Unite d'Immunologie et d'Hematologie, INSERM U. 132, Departement de Pediatrie, Hopital Necker-Enfants Malades; Unite d'Oncologie Virale, Institut Pasteur, Paris, France. The spectrum of lymphadenopathy-associated virus/human T-cell lymphotropic virus type III (LAV/HTLV-III) infections in infants was examined to define early risk factors in order to try to distinguish as early as possible the patients at risk for AIDS. This information would provide a framework for more rational selection of patients who might benefit from new therapeutic approaches and might also help to identify patients who are most likely to be susceptible to opportunistic infections and who therefore might benefit from more aggressive preventive treatment. Eighteen infants were examined because of LAV/HTLV-III infection, 15 of whom, by virtue of the presence of opportunistic infections or lymphoid interstitial pneumonitis, could have been said to have AIDS. Even so, the clinical course and outcome were very different among patients: 8 infants were severely affected, and 10 others had stable symptoms during follow-up. Most clinical findings were comparable in the two groups. Antigen-induced proliferative responses were normal in 10 patients who had a stable course, but were profoundly impaired in 8 others who died or were In poor condition with opportunistic infections. These results correlated with antigen skin tests. Abnormal antibody responses and a peculiar profile of LAV/HTLV-III antibodies were frequently observed in these eight patients. Responses to AB red blood cell antigens, tetanus and diptheria toxoids, polioviruses 1, 2, and 3 and Candida albicans, which were detected in patients with stable disease, were frequently absent in these patients, with no patient responding to more than half of the tested antigens. Antibody production to three antigens of the virus, GP110, P18 and P25 core proteins, changed over the average 18-month followup. Antibodies to GP110 were found in the serum of all 18 patients, whereas antibodies to P18 and P25 were found in eight and nine patients, respectively, with stable disease and in only one and two patients whose condition worsened. The authors suggest that, because no clinical observations appear to be useful in allowing an early prognosis for infants infected with LAV/HTLV-III, three biologic measurements might be considered: (1) in vitro and in vivo cellular responses to antigens; (2) antibody production after immunization; and (3) pattern of serum antibody to the various LAV/HTLV-III antigens. 3A2-Bla-1 Method: Sample Size: Policy Keys: Consecutive patients were studied longitudinally (mean follow-up, 19.5 months; range, 3 to 42 months). Clinical, immunologic, and virologic data were obtained for all subjects, including testing for antibody response to LAV/HTLV-IIL. Eighteen infants infected with LAV/HTLV-III were studied, including 12 patients born to mothers with LAV/HTLV-III infection and 6 patients who were infected by blood products administered during the first weeks of life. The infants ranged in age from 4 to 24 months at diagnosis. 1) Definition of AIDS: Opportunistic Infections (I[IA2), 2) Populations: Pediatric Cases (IA4) Author(s): Title: Source: Institution: Findings: Method: Kovacs, Joseph A., MD; Hiemenz, John W., MD; Macher, Abe M., MD; Stover, Diane, MD; Murray, Henry W., MD; Shelhamer, James, MD; Lane, H. Clifford, MD; Urmacher, Carlos, MD; Honig, Christine, MD; Longo, Dan L., MD; Parker, Margaret M., MD; Natanson, Charles, MD; Parrillo, Joseph E., MD; Fauci, Anthony S., MD; Pizzo, Philip A., MD; Masur, Henry, MD. Pneumocystis carinii Pneumonia: A Comparison Between Patients with the Acquired Immunodeficiency Syndrome and Patients with Other Immunodeficiencies. Annals of Internal Medicine, May 1984, Vol. 100, No. 5: 663-671. Critical Care Medicine Department, Clinical Center, Pediatric Branch, Medicine Branch, and Laboratory of Pathology, National Cancer Institute, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Pulmonary Division, Department of Medicine, and Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York; Infectious Disease Division, Department of Medicine, and Department of Pathology, New York Hospital-Cornell Medical Center, New York, New York. This early descriptive report compares the features of Pneumocystis carinii pneumonia in AIDS patients with those in patients with other diseases affecting the immune system. At presentation, patients with AIDS were found to have a longer median duration of symptoms (28 days versus 5 days), lower mean breathing rate (23.4 versus 30 per minute), and higher median concentration of oxygen in the blood. All of these differences were statistically significant. The survival rate from 1979 to 1983 in the two groups was similar (57% in the AIDS group versus 60% in the patients with other immunosup- pressive disorders, survival rates for patients with AIDS subsequently has improved). Patients with AIDS had a higher incidence of adverse reactions to therapy with trimethoprim-sulfamethoxazole (22 of 34 versus 2 of 17). Survivors with AIDS at initial presentation had a significantly lower breathing rate, higher concentration of oxygen in the blood, higher counts of certain white blood cells (lymphocytes), and higher levels of a specific protein (albumin) in the blood than did nonsurvivors. P. carinii pneumonia has a different, more insidious clinical picture in patients with AIDS than in those with other diseases affecting the immune system. Therapy with trimethoprim-sulfamethoxazole for P. carinii pneumonia in AIDS patients is complicated by frequent adverse reac- tions. This study was a retrospective analysis of cases of P. carinii pneumonia in AIDS patients compared with patients with other diseases affecting the immune system. Medical charts of all subjects were reviewed. Diagnosis of P. carinii pneumonia was based on finding three or more typical disease organisms in specimens of lung secretions or in lung tissue 3A2-Kov-2 Sample Size: Policy Keys: obtained through a bronchoscope, from a biopsy (open lung or puncture through the chest), or at autopsy. Forty-nine episodes of P. carinii pneumonia in AIDS patients were compared with 39 episodes in patients with other immunosuppressive diseases from the National Institutes of Health from January 1970 to June 1983 and the New York Hospital and Memorial-Sloan Kettering Cancer Center from 1979 through March 1983. The AIDS group consisted of 45 males and | female; 42 of this group were homosexual or bisexual, 1 was an intravenous (I.V.) drug user, | was Haitian, and 2 had no known risk factors; their ages ranged from 25 to 57 years (median, 35). The other disease group consisted of 26 males and 13 females; none were homosexual, I.V. drug users, or Haitians; their ages ranged from 10 to 69 years (median, 33); 30 of the group had blood system malignancy (such as leukemia), 5 had vasculitis (inflammation of a blood vessel or lymphatic vessel), and 4 had other immunosuppressive diseases. 1) Diagnostic Definitions of AIDS: P. carinii Pneumonia (IlIA2), 2) Treatment: Symptom Management (IVB) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lerner, Chester W., MD; Tapper, Michael, L. MD. Opportunistic Infection Complicating Acquired Immune Deficiency Syndrome: Clinical Features of 25 Cases. Medicine, 1984, Vol. 63, No. 3: 155-164. Section of Infectious Diseases, Department of Medicine, Lenox Hill Hospital, New York, New York. The purpose of this study was to evaluate and characterize the clinical syndrome in 25 early cases of AIDS complicated with opportunistic infections seen in a hospital in New York City. All patients were followed up until their deaths or for a minimum of | year through September 1983. Twenty-two patients were initially diagnosed as having AIDS after presenting with opportunistic infections. A total of 70 different types of infections were diagnosed, the commonest being Candida albicans, Pneumocystis carinii pneumonia, cytomegalovirus, and Mycobacterium avium-intracellulare. Less frequent pathogens included Cryptococcus neoformans (a fungus that attacks skin, lungs and brain), Toxoplasma gondii, Cryptosporidium, and tuberculosis. Seven men also had Kaposi's sarcoma. Prodromal syndromes lasted up to 8 months before the diagnosis of AIDS. Disseminated infections with atypical mycobacteria and cytomegalovirus were the leading causes of death. Bone marrow biopsies revealed a cellular abnormality in 82% of cases, but only occasionally yielded an infectious agent. By January 1984, 23 (92%) of the patients had died. Two other patients were alive at 17 and 16 months. This was a long-term follow-up study of 25 AIDS patients diagnosed in New York City between March 1981 and September 1982. Biopsy or autopsy specimens were examined, including lung, liver, gastrointestinal tract, adrenals, bone marrow, and brain tissue. Standard tests were run for antibodies in the blood that indicated exposure to hepatitis B virus, Epstein-Barr virus, and cytomegalovirus. White blood cell counts were performed, and serum immunological levels were measured by radial immunodiffusion. T-cell subpopulations were determined with monoclonal antibodies OKT#4 and OKT&. In a New York City hospital, | woman and 24 men with AIDS were identified and studied; 18 patients were white, 2 black, and 5 Hispanic. Of the total, 23 patients were homosexual or bisexual men, including 1 intravenous ([.V.) drug user, and 2 were heterosexual [.V. drug users, including the sole woman. 1) Clinical Manifestations: Opportunistic Infections (llIA2), 2) Incubation Period and Disease Stages (IIIC) 3A2-Ler-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Whiteside, Mark E.; Barkin, Jamie, S.; May, Richard G.; Weiss, Stephen D.; Fischl, Margaret A.; MacLeod, Caroline L. Enteric Coccidiosis Among Patients with the Acquired Immunodeficiency Syndrome. The American Journal of Tropical Medicine and Hygiene, 1984, Vol. 33, No. 6: 1065-1072. Division of Tropical Medicine, Department of Epidemiology and Public Health, and Divisions of Gastroenterology and General Medicine, Department of Medicine, University of Miami School of Medicine, Miami, Florida. To describe the clinical manifestations, diagnosis, and therapy of infections of the gastrointestinal system, this article reports data for 10 patients with AIDS. All patients presented with diarrhea. Infecting organisms were Cryptosporidium species in seven cases and Isospora belli in three others; these organisms are part of a group of infections called enteric coccidiosis (a set of severe intestinal diseases caused by a particular protozoan parasite). Special techniques were used to identify the infecting organisms in the feces. Six of the 10 patients had enteric coccidiosis as the initial manifestation of AIDS. Spiramycin was the only drug effective in treating infection with Cryptosporidium species. Patients with [. belli infection responded to prolonged treatment with trimethoprim-sulfamethoxazole. Medical case reports of 100 AIDS cases from the Jackson Memorial Hospital, Jackson, Florida, between June 1981 and June 1983 were reviewed. Of the 30 AIDS patients initially evaluated for gastro- intestinal illness, 10 were diagnosed as having infections of the coccidiodal group. Stool samples were examined for parasite eggs and organisms by microscopy. Small intestinal biopsies were taken from the jejunum area, stained, and examined microscopically for organisms. The duodenal string test was also used, in which the patient swallows a capsule containing a piece of string, which picks up mucus containing parasites as it passes through the intestines. Ten Florida patients with AIDS and gastrointestinal infection were studied, including five homosexual men (average age, 40.8 years) and five adult Haitians (average age, 32.4 years). 1) Diagnostic Definitions of AIDS: Opportunistic Infections (IIIA2), 2) Treatment: Symptom Management (IVB), 3) Diagnostic Indicators (IIIA 3) 3A2-Whi-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Macher, Abe M., MD; Kovacs, Joseph A., MD; Gill, Vee, PhD; Roberts, Glenn D., PhD; Ames, John, BS; Park, Choong H., PhD; Straus, Stephen, MD; Lane, H. Clifford, MD; Parrillo, Joseph E., MD; Fauci, Anthony S., MD; Masur, Henry, MD. Bacteremia Due to Mycobacterium avium-intracellulare in the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, December 1983, Vol. 99, No. 6: 782-785. Microbiology Service, Clinical Pathology Department; Critical Care Medicine Department, Clinical Center; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Section of Microbiology, Mayo Clinic, Rochester, Minnesota; Department of Pathology, Fairfax Hospital, Falls Church, Virginia. In this study, AIDS patients were tested for the presence of Mycobacterium avium-intracellulare, which has frequently been found in patients with AIDS. Of 30 AIDS patients referred to the National Institutes of Health (NIH) for evaluation, 14 were asymptomatic when tested. Blood cultures for M. avium-intracellulare were negative on one to three occasions. Sixteen patients had fever, malaise, weight loss, and a history of opportunistic infections; 6 of these 16 patients had never had M. avium-intracellulare cultured from any site. Ten of the 16 patients were known to have M. avium-intracellulare; 7 of these had one or more positive blood cultures. Different tests used for culturing M. avium-intracellulare were compared. The Bactec system may provide a more rapid method for documenting this infection than the Dupont isolator system. The relative sensitivity of these two systems should be evaluated further. For AIDS patients, the detection and quantification of mycobacteria in the blood should be considered as a method for assessing the prognosis and efficacy of antimycobacterial therapy. In this study, the Bactec and Dupont isolation systems were compared for culturing M. avium-intracellulare from AIDS patients. Extensive immunologic testing was performed, including measures of T and B cells, sensitivity to a panel of mitogens and specific antigens, interferon levels, natural killer cell activity, cytomegalovirus-specific cellular activity, and serum immunoglobulin levels. All tests were done by standard methods. Blood samples were cultured for M. avium-intracellulare after Dupont isolation, kept in an incubator for 6 weeks, and examined daily. Blood and marrow samples were also cultured for M. avium-intracellulare in the Bactec X-ray system. A group of 30 AIDS patients referred to NIH for evaluation were studied. Of the group, 14 had one or more life-threatening opportunistic infections without Kaposi's sarcoma, 7 had Kaposi's sarcoma without opportunistic infection, and 9 had both Kaposi's sarcoma and opportunistic infection. All met Centers for Disease Control criteria for diagnosis of AIDS. 3A2-Mac-5 Policy Keys: 1) Clinical Manifestations: M. avium-intracellulare (IIIA2), 2) Diagnostic Indicators (IIIA3) III. Characteristics of Disease A. Diagnostic Definitions and Clinical Manifestations of AIDS 3. Diagnostic Indicators Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Bigby, Timothy D.; Margolskee, Dorothy; Curtis, Jeffrey L.; Michael, Philip F.; Sheppard, Dean; Hadley, W. Keith; Hopewell, Philip C. The Usefulness of Induced Sputum in the Diagnosis of Pneumocystis carinii Pneumonia in Patients with the Acquired Immunodeficiency Syndrome. American Review of Respiratory Disease, 1986, Vol. 133: 515-518. Medical Service and Clinical Laboratory, San Francisco General Hospital Medical Center; Department of Medicine, Cardiovascular Research Institute, and Department of Laboratory Medicine, University of California, San Francisco, California. This study evaluates sputum examination as a procedure for establishing the diagnosis of Pneumocystis carinii pneumonia in patients with AIDS. Twenty-five of 32 patients were ultimately determined to have P. carinii pneumonia. Of these, 14 (56%) were identified by sputum examination. Of 18 patients whose sputum did not contain P. carinii, 11 patients (with a false-negative sputum examination) had the organism detected by bronchoscopy. There were no clinical features that identified patients more likely to have a positive sputum examination, and no additional treatable pathogens appeared to be missed by sputum examination. The authors demonstrate that examination of induced sputum establishes the diagnosis of P. carinii pneumonia in a significant proportion of patients and that, although a negative result cannot be relied on without further investigation (i.e., bronchoscopy), this technique can decrease the need for more invasive procedures. To prospectively evaluate the usefulness of induced sputum as a noninvasive technique in the diagnosis of P. carinii pneumonia, specimens of collected sputum induced by inhalation of 3% saline were examined by Giemsa stain. Specimens that revealed P. carinii were processed for mycobacteria and fungi; specimens that were negative for P. carinii were not further processed, but additional patient specimens were obtained within 24 hours by bronchoscopy and stained with Giemsa stain. Fluid and tissue were then cultured for mycobacteria, fungi, and viruses by standard techniques. Patients who had induced sputum that revealed P. carinii were begun on therapy, unless contraindicated; if, after 5 to 7 days of therapy, the patient failed to improve, bronchoscopy was recommended to exclude a second pathogen. Patients were divided into three groups for analysis: those whose sputum revealed P. carinii, those whose sputum was truly negative, and those who had false-negative sputum results. Groups were compared by age and clinical characteristics. Thirty-two patients, of a total of 43 consecutive patients with or suspected of having AIDS and meeting criteria for bronchoscopy, were included in the study. Eleven of the 43 patients were excluded: 9 were too ill to cooperate with sputum induction and 2 refused. 1) Definitions of AIDS: Diagnostic Indicators (I[IA3) 3A3-Big-1 Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Boyko, William J., MD, FRCPC; Schechter, Martin T., MD, MSc, PhD; Constance, Peter, MB, BS; Nitz, Rod, MD. Limited Usefulness of Lymphocytopenia in Screening for AIDS in Hospital Patients. Canadian Medical Association Journal, 15 August 1985, Vol. 133: 293. St. Paul's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada. To evaluate the usefulness of testing for lymphocytopenia as a screening test for AIDS, this study determined the prevalence of lymphocytopenia In 625 patients consecutively admitted to an acute-care university Lenching hospital. Absolute lymphocytopenia (lymphocyte count of less than 107/L) was present in 91 (15%) of these patients at admission; 25 (4%) had lymphocyte counts of less than 0.5 x 107/L. Clinical conditions associated with lymphocytopenia included infection (20 patients), trauma or surgery (13), malignant disease (12), cardiac disease (12), inflammation (8), acute bleeding (7), connective-tissue disease (6), and kidney failure (3). Of 32 AIDS patients, 13 (41%) had a lymphocyte count of lesg than 1 x 10%/L and 4 (13%) had a lymphocyte count of less than 0.5 x 107/L. The positive predictive value of using lymphocytopenia to screen for AIDS was negligible (0.003); the positive likelihood ratio was 2.7, indicating that absolute lymphocyte counts in hospitalized patients should not be used as the sole means of identifying patients at high risk for AIDS. Patients admitted to an acute-care university teaching hospital were tested for apsolute lymphocytopenia (defined as a lymphocyte count of less than 107/L). For comparison, patients at this hospital diagnosed as having AIDS were also tested for lymphocytopenia. (Enumeration tech- niques were not specified.) Subjects included 625 patients consecutively admitted to an acute-care university teaching hospital in Vancouver, British Columbia, Canada, and 32 AIDS patients diagnosed over an 18-month interval (18 with Kaposi's sarcoma, 12 with opportunistic infection, and 2 with lymphoma). 1) Diagnostic Definitions: Diagnostic Indicators (II[A3), 2) Immunological Aspects (IIIE), 3) Geographic Trends: Canada (IB1) 3A3-Boy-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Broaddus, Courtney, MD; Dake, Michael D., MD; Stulbarg, Michael S., MD; Blumenfeld, Walter, MD; Hadley, W. Keith, MD; Golden, Jeffrey A., MD; Hopewell, Philip C., MD. Bronchoalveolar Lavage and Transbronchial Biopsy for the Diagnosis of Pulmonary Infections in the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, June 1985, Vol. 102, No. 6: 747-752. Chest Division, Medical Service, and Microbiology Laboratory, San Francisco General Hospital Medical Center; Departments of Medicine and Laboratory Medicine, and Cardiovascular Research Institute, University of California, San Francisco, California. This study examined the effectiveness of two special techniques in diagnosing lung infections in AIDS patients: transbronchial biopsy and bronchoalveolar lavage (washing). A total of 173 different infectious agents were found in 171 patients with AIDS. The initial evaluation with the bronchoscope yielded positive results in 96% of the patients. Bronchoscopy, with lavage and biopsy, showed infection in 98%. These methods diagnosed 100% of infections with Pneumocystis carinii pneumonia (100% sensitivity). When used alone, examination of biopsy specimens or lavage specimens showed infections in fewer subjects (86% and 87%, respectively). The authors conclude that bronchoscopy with examination of both lavage specimens and tissue specimens is a very accurate means of diagnosing lung infections in AIDS patients. This study was a comparative analysis of two special procedures for diagnosing pulmonary infections in AIDS patients. For each subject, the initial diagnostic examination by bronchoscope was conducted under sedation and local anesthesia and included visual inspection (through the fiber optic bronchoscope) of the trachea and the major bronchi, bronchoalveolar lavage, and removal through the tube of tissue samples from the right lower lobe for biopsy. In the few patients whose chest x- rays showed localized involvement in particular areas of the lungs, lavage and biopsy were done in the area of greatest abnormality. A total of 276 separate procedures were performed for 171 patients with AIDS and pulmonary infections between August 1981 and March 1984 at the San Francisco General Hospital and the Moffitt-Long Hospital in San Francisco. 1) Diagnostic Indicators (IIIA3), 2) Diagnostic Definitions of AIDS: P. Carinii Pneumonia (IIIA2) 3A3-Bro-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Fuchs, D.; Hausen, A.; Reibnegger, G.; Reissigl, H.; Schonitzer, D.; Spira, T.; Wachter, H. Urinary Neopterin in the Diagnosis of Acquired Immune Deficiency Syndrome. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. 1: 70-71. Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck (Fuchs, Hausen, Reibnegger, Wachter); Blood Transfusion Center, University of Innsbruck, Innsbruck, Austria (Reissigl, Schonitzer); Division of Host Factors, Centers for Disease Control, Atlanta, Georgia (Spira). This study was designed to ascertain whether elevated neopterin levels, which have been found in patients suffering from certain types of cancer and viral diseases, could be used as a marker for AIDS in high-risk populations and in blood donors. Neopterin levels in the urine of 35 of 38 AIDS patients were significantly higher than in the control group. In 52 of 64 patients with generalized lymphadenopathy, levels were above the normal upper limits. Ten of 11 clinically healthy patients with hemophilia also had extremely high neopterin levels. Levels in all 20 controls from the U.S. were normal and comparable to levels in 417 healthy subjects in Austria in a previous study. Neopterin levels in the urine of 14 of 198 blood donors were above the normal limit. The authors conclude that both AIDS and lymphadenopathy patients show a high incidence of elevated neopterin levels. Urine samples were obtained and frozen. Neopterin levels were determined by high-pressure liquid chromatography. There were 38 AIDS patients, 64 lymphadenopathy patients, Il hemophiliacs, and 20 controls from the Centers for Disease Control. These were compared with 198 Austrian male volunteers (aged 18 to 25 years) and 417 healthy Austrian volunteers in a previous study on neopterin levels and lymphoid neoplasms. 1) Diagnostic Definitions of AIDS: Diagnostic Indicators (IIIA3), 2) Immunological Aspects (IIE), 3) Populations: Hemophiliacs (IA 3) 3A3-Fuc-4 Source: Institution: Findings: Method: Sample Size: Policy Keys: Moon, Kirk L. Jr., M.D.; Federle, Michael P., M.D.; Abrams, Donald I., M.D.; Volberding, Paul, M.D.; Lewis, Brian J., M.D. Kaposi Sarcoma and Lymphadenopathy Syndrome: Limitations of Abdominal CT in Acquired Immunodeficiency Syndrome. Radiology, February 1984, Vol. 150, No. 2: 479-483. Departments of Radiology (Moon, Federle) and Medicine (Abrams, Volberding, Lewis), University of California School of Medicine and San Francisco General Hospital, San Francisco, California. Abdominal and pelvic computed tomography (CT) scans were performed on 34 patients with biopsy-proven localized and diffuse Kaposi's sarcoma (KS) and on 12 male homosexual patients with lymphadenopathy syndrome of at least 3 months' duration involving two or more sites outside the groin, confirmed on physical exam by the patient's physician. Abdominal CT abnormalities were extremely common in patients with AIDS-related KS, with two-thirds of cases demonstrating lymphadeno- pathy and splenomegaly (enlarged spleen), and 82% demonstrating rectal and perirectal abnormalities. These findings are not necessarily indicative of widespread malignancy, however, since similar types and numbers of CT abnormalities are detected in homosexual males with lymphadenopathy and no evidence of KS. The authors conclude that abdominal CT, in itself, is of limited value in the diagnostic evaluation of patients with KS, except insofar as it defines abnormalities that can then be pursued with more specific diagnostic techniques (such as biopsy). Abdominal CT scans were used to compare patients with KS and lymphadenopathy syndrome. A group of 34 patients with biopsy-proven localized and diffuse KS were studied; their ages ranged from 21 to 76 years (mean, 38). Of this group, 31 were homosexually active men thought to have the AIDS-related form of KS, and 3 were older men aged 56 to 76 (mean, 65) thought to have the classic, pre-epidemic type of KS. Also studied were 12 male homosexual patients with lymphadenopathy symdrome; their ages ranged from 24 to 42 years (mean, 34). The latter group met Centers for Disease Control criteria for lymphadenopathy syndrome. 1) Diagnostic Indicators (IlIA3), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA1) 3A3-Moo-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Wollschlager, Christine M., MD; Khan, Faroque A., MB, FCCP; Chitkara, Rajinder K., MD, FCCP; Shivaram, Urmila, MD. Pulmonary Manisfestations of the Acquired Immunodeficiency Syndrome (AIDS). Chest, February 1984, Vol. 85, No. 2: 197-202. Division of Pulmonary Medicine, Department of Medicine, Queens Hospital Center Affiliation of the Long Island Jewish-Hillside Medical Center; School of Medicine, Health Sciences Center, State University of New York, Stony Brook, New York. Fifteen New York AIDS patients with pulmonary infections were analyzed in this study. Fourteen of 15 patients had Pneumocystis carinii pneumonia at the time of evaluation. Chest x-rays showed no uniform pattern which was predictive of P. carinii pneumonia. However, all 13 patients tested had clear abnormalities in oxygenation of their blood (as reflected in analysis of an arterial blood sample). The most common pulmonary finding in the patients studied was infection. Fourteen had P. carinii pneumonia, which was readily diagnosed by transbronchial fiber optic lung biopsy in & patients, and 5 patients were found to have disseminated Mycobacterium avium-intracellulare, which often developed after recovery from P. carinii pneumonia. Drug therapy for P. carinii pneumonia with trimethoprim- sulfamethoxazole was unsuccessful in 8 of 10 patients; 4 of these 8 failures responded to a second drug (pentamidine). Mortality was 100% in patients who had AIDS for more than | year, and 70% in those with AIDS less than | year. Despite appropriate drug therapy, mortality rates for these patients are high and apparently unaffected by appropriate drug therapy for the pneumonias. This was a retrospective analysis describing cases of AIDS with pulmonary infection. Records of all AIDS patients seen by the hospital's pulmonary service were reviewed and assessed. When possible, information was obtained prospectively and/or confirmed at autopsy. The study included 15 patients with AIDS and pulmonary infections who were reported from the Pulmonary Division of the Queens Hospital, Queens, New York, between [981 and July 1983. There were 13 men and 2 women ranging in age from 23 to 43 years (mean, 32). Three patients were of Haitian heritage, one was homosexual, one was homosexual and an intravenous (I.V.) drug abuser, one had no known risk factor, and nine were [.V. drug abusers. 1) Diagnostic Indicators (IIIA3), 2) Treatment: Symptom Management (IVB), 3) Diagnostic Definitions of AIDS: P. Carinii Pneumonia (I11A2) 3A3-Wol-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Blumenfeld, Walter, MD; Wagar, Elizabeth, MD; Hadley, W. Keith, MD, PhD. Use of the Transbronchial Biopsy for Diagnosis of Opportunistic Pulmonary Infections in Acquired Immunodeficiency Syndrome (AIDS). American Journal of Clinical Pathology, January 1984, Vol. 81, No. 1: 1- 5 Department of Laboratory Medicine, University of California and Clinical Laboratories, San Francisco General Hospital-Medical Center, San Francisco, California. In an effort to provide rapid and accurate diagnosis of AIDS conditions in the lungs, the authors evaluated the use of bronchoscopy and transbronchial biopsy. In particular, they evaluated the efficacy of diagnosing infections by a special, more rapid treatment of the biopsy specimens -- touch preparation with Giemsa staining of the tissue samples. This was compared with standard preparation of tissue specimens. Fifty-nine transbronchial biopsies and eight open lung biopsies taken from 38 patients with clinical and laboratory features of AIDS were examined to determine the cause of their pulmonary disease. Pneumocystis carinii pneumonia was diagnosed in 16 patients. When sufficient material was available, the rapid Giemsa-stained touch preparation result agreed with the standard, slower specimen preparation result. When the rapid-preparation specimens were cultured, seven of the patients with P. carinii pneumonia also had cytomegalovirus (CMV) infection. Six additional patients had CMV infection without P. carinii pneumonia. Mycobacterial and fungal infections were also identified in these six patients. Sixteen patients had no specific diagnosis. (Reviewer note: Induced sputum techniques, which are inexpensive and non- invasive, are now performed routinely.) This study was a retrospective analysis of records and biopsy specimens for patients with pulmonary disease and AIDS. Tissue was fixed in Formalin, stained, and examined microscopically by standard methods. Parallel specimens were used for culture and touch preparations. From 38 patients, 59 transbronchial biopsies and eight open-lung biopsies were obtained at the San Francisco General Hospital. Dates of patient accrual are not stated. 1) Diagnostic Indicators (IIIA3), 2) Opportunistic Infections (IIIA2) 3A3-Blu-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kern, P.; Meigel, W.; Euler, H.H.; Dietrich, M. Beitrag Immunologischer ~~ Untersuchungen zur Definition der Abwehrschwache bei AIDS (The Contribution of Immunological Investigation to the Definition of Weakness of Resistance in AIDS). Offentliches Gesundheits-Wesen, 1984, Vol. 46: 445-448, Bernhard-Nocht-Institut fur Schiffs- und Tropenkrankheiten (Klinische Abteilung) (Kern, Dietrich), Hamburg; Allgemeines Krankenhaus St. Georg (Dermatol. Abteilung) (Meigel), Hamburg; II. Medizinische Klinik, Universitat Kiel, Federal Republic of Germany (Euler). Cellular immune insufficiency affects particularly the system of helper T cells, a T-cell subpopulation. Since many other viral infections bring about a shift in the T-cell subpopulations, additional immunological parameters are needed to make a diagnosis of AIDS or its prodromal stage, lymphadenopathy syndrome (LAS). This study was undertaken to help establish these parameters. The results confirm the shift in T-cell subpopulations, for instance, in cytomegalovirus (CMV)-induced mononucleosis. Furthermore, their results show that by counting HLA-DR-positive lymphocytes, it is possible to differentiate immunologically between LAS and CMV infection by the distribution of phenotypes. Levels of circulating immune complexes are clearly ‘elevated in infectious diseases, but also in malignant diseases. The total immunoglobulin level in serum was elevated with AIDS or LAS. Neopterin turns out to be an unspecific sign, since it is elevated in other illnesses, particularly viral infections. This was an immunological and clinical investigation of homosexual men (with or without clinical symptoms of AIDS or LAS), patients with CMV, Epstein-Barr virus (EBV) infection or acute viral hepatitis, and patients with leprosy. Subject groups consisted of 80 German homosexual men (with or without clinical symptoms of AIDS or LAS); 39 German patients with CMV, EBV, or acute viral hepatitis; and 15 German patients with lepromatous leprosy. 1) Diagnostic Definitions of AIDS: Diagnostic Indicators (IlIA3), 2) Immunological Aspects (IIE), 3) Precursors of AIDS (IIIB) 3A3-Ker-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kern, P.; Rokos, H.; Dietrich, M. Raised Serum Neopterin Levels and Imbalances of T-Lymphocyte Subsets in Viral Diseases, Acquired Immune Deficiency and Related Lymphadenopathy Syndromes. Biomedicine and Pharmacotherapy, 1984, Vol. 38: 407-411. Clinical Department, Bernhard-Nocht-Institut fur ~~ Schiffs-und Tropenkrankheiten (Tropical Institute), Hamburg (Kern, Dietrich); Research Laboratory, Henning Berlin, Berlin, Federal Republic of Germany (Rokos). Since there is evidence that activation of T-lymphocytes raises neopterin (a biochemical of putative immunorelevance, which is excreted in the urine) levels, this study investigates the value of neopterin as a new biochemical marker for clinical assessment of cell-mediated immune responses. Neopterin level was found to be significantly elevated in the sera of 42 of 45 homosexual patients with AIDS and related lymphadeno- pathy syndrome, 19 of 19 patients with Epstein-Barr virus or cytomegalo- virus infections, and patients with acute hepatitis. Although neopterin levels correlated with the inversion of the helper/suppressor T-cell ratio, the quantitative enumeration of individual lymphocyte subsets was not correlated with neopterin level. Neopterin seems to be released under various conditions in viral diseases and may reflect a functional state of T-lymphocytes irrespective of the actual number expressing differentia- tion antigens on the cell surface. Blood serum samples were obtained and tested for total number of T- lymphocytes, T-lymphocyte subpopulations, and neopterin level, all by standard methods. Eighty-five patients with viral or suspected viral infections were studied, including 7 patients with AIDS (one of whom was deceased), 2 African patients with opportunistic infections indicative of underlying cellular immune deficiency, 38 homosexual patients with unexplained lymph- adenopathy, 20 patients with acute hepatitis, 8 with Epstein-Barr virus, and 10 with cytomegalovirus. The control group consisted of 35 healthy homosexual men and 17 heterosexual men of comparable age. 1) Diagnostic Indicators (IIIA3), 2) Immunological Aspects (IIIE) 3A3-Ker-9 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Coleman, Diana Lewis; Dodek, Peter M.; Luce, John M.; Golden, Jeffrey A.; Gold, Warren M.; Murray, John F. Diagnostic Utility of Fiberoptic Bronchoscopy in Patients with Pneumocystis carinii Pneumonia and the Acquired Immune Deficiency Syndrome. American Review of Respiratory Disease, November 1983, Vol. 128, No. 5: 795-799. Chest Division, Medical Service, San Francisco General Hospital Medical Center; Division of Pulmonary Diseases, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, California. Records of male patients with suspected Pneumocystis carinii pneumonia and AIDS were evaluated to determine the diagnostic utility of fiberoptic bronchoscopy. Of the 24 patients shown to have P. carinii pneumonia, 22 were diagnosed by bronchoscopy. Twenty patients were diagnosed after one broncho- scopy and two patients after two bronchoscopies. The sensitivity of bronchoscopy specimens for diagnosing P. carinii pneumonia was 79% for transbronchial biopsies (tissue specimens obtained through the bronchi) and 39% for bronchial brushings (cells rubbed off and retrieved). The overall sensitivity of fiber optic bronchoscopy was 85%. Complications, occurring during 6 of the 37 bronchoscopies, were slight hemoptysis (hemorrhage), fever, septic shock, and pneumothorax (air in the chest cavity). Fiber optic bronchoscopy was found to be a safe and effective initial diagnostic procedure, which had the added benefit of allowing diagnosis of coexisting lung disease. A mail survey was conducted of 210 infectious disease and pulmonary medicine specialists in the San Francisco Bay area. Responses were received from 70 (33%) of the physicians. From among these responses, 35 patients were identified for retrospective study who had had fiber optic bronchoscopy for suspected P. carinii pneumonia. Patients' hospital charts were reviewed and comparable data were compiled. Statistical calculations were made based on whether patients had biopsy-proven P. carinii pneumonia. oo A group of 35 adult male San Francisco patients seen in 1981 and 1982 were selected, all of whom had had fiber optic bronchoscopy for suspected P. carinii pneumonia. Patients with known malignancies other than Kaposi's sarcoma or receiving immunosuppressive therapy were excluded. The 35 patients came from seven San Francisco Bay area hospitals. Patients diagnosed with P. carinii pneumonia had a mean age of 37.2 years, while those without P. carinii pneumonia had a mean age of 34.8 years. Of the 35 patients, 30 were homosexual, 4 were bisexual, and | was heterosexual. The pneumonia group did not differ from the nonpneumonia group in age, sexual preference, or duration of illness before seeking medical attention. Patients in both groups had a frequent history of hepatitis, gonorrhea, syphilis, and amoebiasis (infection with 3A3-Col-10 disease-producing amoebae). Symptoms and physical findings were similar for the two groups. Policy Keys: 1) Diagnostic Indicators (IlIA3), 2) Diagnostic Definitions of AIDS: P. Carinii Pneumonia (IIIA2) III. Characteristics of Disease A. Diagnostic Definitions and Clinical Manifestations of AIDS 4, Other Clinical Manifestations Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Tuberculosis and Acquired Immunodeficiency Syndrome--Florida. Morbility and Mortality Weekly Report, 19 September 1986, Vol. 35, No. 37: 587-539. Centers for Disease Control, Atlanta, Georgia. Concern about a possible association between human T-cell lymphotropic virus type Ill/lymphadenopathy-associated virus (HTLV-III/LAV) infection and increased numbers of tuberculosis (TB) cases led to an evaluation of data on AIDS and TB. Of the 1,094 persons with AIDS reported in Florida between 1981 and 1985, 109 (10%) were also diagnosed between 1978 and 1985 as having TB. The number of cases of AIDS with TB rose from zero in 1981 to a peak of 55 in 1984 and dropped off to 26 in 1985. The interval between report of TB and diagnosis of AIDS ranged from 7 years before to 15 months after (median, 3 months before); 62 cases (57%) were reported to have TB more than 1 month before AIDS diagnosis, 30 (28%) within 1 month before or after, and 17 (16%) more than 1 month after. Of the 7,241 persons in Florida reported as having TB between 1981 and 1985, 105 (2%) also had AIDS (the remaining 4 patients with AIDS and TB had TB reported before 1981 and were excluded from analysis due to lack of detailed information). The number and proportion rose from 5 of 1,553 (<1%) in 1981 to 33 of 1,335 (3%) in 1984 and fell to 23 of 1,425 (2%) in 1985. This was a surveillance study of patients in Florida with both AIDS and TB reported between 1978 and 1985. A total of 109 AIDS patients in Florida were reported as having TB before or after diagnosis of AIDS. AIDS patients with TB were similar to AIDS patients without TB in age and sex, but among the patients with TB there were more blacks (81% versus 37%), more foreign-born individuals (60% versus 25%), and fewer homosexuals and bisexuals (21% versus 62%). TB patients with AIDS were younger than TB patients without AIDS (median, 30 years versus 49 years) and more likely to be black (79% versus 57%), male (83% versus 71%), and foreign born (60% versus 21%). Of the 105 male patients with TB reported after 1981, 65 (60%) lived in Dade County while 23 (22%) lived in Palm Beach County. 1) Other Clinical Manifestations (IlIA4), 2) Populations: Minorities (IA5) 3A4-Cen-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Abrams, Donald I[., MD; Kiprov, Dobri D., MD; Goedert, James J., MD; Sarngadharan, M.G., PhD; Gallo, Robert C., MD; Volberding, Paul A., MD. Antibodies to Human T-Lymphotropic Virus Type Ill and Development of the Acquired Immunodeficiency Syndrome in Homosexual Men Presenting with Immune Thrombocytopenia. Annals of Internal Medicine, January 1986, Vol. 104, No. 1: 47-50. San Francisco General Hospital; Children's Hospital, San Francisco, California; National Cancer Institute, Bethesda, Maryland; Litton Bionetics, Inc., Kensington, Maryland. Thirty-five homosexual men with Immune thrombocytopenia were evaluated and treated from January 1982 through December 1984. Treatment involved steroid therapy for 24 patients and splenectomy (surgical removal of the spleen) for 15 patients (some of whom had had steroid therapy with no response). Three patients who had had steroid therapy (two with prednisone) developed AIDS 14 to 34 months (mean, 28 months) after initial diagnosis. All patients had immune dysfunction and lowered T-cell ratios, with a mean helper/suppressor T-cell ratio of 0.4 and an absolute depletion of helper cells to 390 per mm~. Of 25 patients tested for antibody to human T-cell lymphotropic virus type III (HTLV- ll), 21 were positive and 4 were borderline; Western blot analysis confirmed seropositivity in these 4. Twenty patients had peripheral lymphadenopathy, and six patients had minimal splenomegaly. Two patients had oral candidiasis at initial evaluation. All 25 patients who had bone marrow aspirations and biopsies performed showed adequate to increased numbers of megakaryocytes (large bone marrow cells that produce blood platelets). Results indicate that immune thrombocytopenia is part of the clinical spectrum of AIDS. Less than 10% of subjects receiving steroid therapy sustained a complete response. Response to splenectomy in this study (66%) was similar to that of patients with classic immune thrombocytopenia. Due to the high incidence of steroid-related side effects, the use of prednisone to treat thrombocytopenia should be reserved for patients with acute significant bleeding episodes. The absence of life-threatening bleeding in these subjects makes no therapy an alternative in AIDS-related immune thrombocytopenia. An enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies to HTLV-II; the substrate was disrupted whole virus produced from the H9 cell line. Sera with ELISA ratios of 5.0 or greater were defined as positive; samples with ratios of less than 3.0 were defined as negative. Intermediate ratios were considered borderline and were retested by Western blot. Twenty-four patients were begun on prednisone (steroid) therapy at a daily oral dose of | mg/kg of body weight. The mean duration of follow-up for the cohort was 20.9 months. Thirty-five homosexual San Francisco men with isolated thrombocyto- penia who were consecutively treated at the AIDS Clinic at San 3A4—-Abr-2 Policy Keys: Francisco General Hospital were studied. Of the group, 32 were white and 3 Hispanic, ages ranging from 23 to 47 years (mean, 33.6). Immune thrombocytopenia was diagnosed in | patient in 1980, 4 in 1982, 18 in 1983, and 12 in 1984. Twenty-two (63%) were diagosed between the months of April and July. 1) Other Clinical Manifestations: Thrombocytopenia (I[IA%), 2) Immuno- logical Aspects (IIIE), 3) Treatment: Symptom Management (IVB) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Tavitian, Avedis, MD; Raufman, Jean-Pierre, MD; Rosenthal, Linda E., MD. Oral Candidiasis as a Marker for Esophageal Candidiasis in the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, January 1986, Vol. 104, No. 1: 54-55. State University of New York, Downstate Medical Center, Brooklyn, New York. Although oral and esophageal candidiasis are common among AIDS patients, the relationship between infection at each site is unknown. This study prospectively evaluated patients with AIDS and oral candidiasis to determine whether the oral lesion may be sufficient to indicate esophageal involvement as well, eliminating the need to examine the esophagus directly by endoscopy. All 10 patients with oral candidiasis were also found to have esophageal candidiasis. Although it is possible that clumps of fungi are swallowed from the oral infection site, the density and extent of esophageal involvement in these patients make this an unlikely explanation for the findings. The authors suggest that if patients have symptoms of esophageal disease, therapy should be initiated for esophageal candidiasis. If patients are asymptomatic, only the oral candidiasis is treated. Endoscopy can therefore be reserved for patients who continue to have symptoms despite antifungal therapy, thereby reducing the number of endoscopic procedures. This prospective evaluation of AIDS patients with oral candidiasis evaluated clinical patient data to determine the occurrence of esophageal candidiasis in these patients. Ten AIDS patients with oral candidiasis were evaluated. Pneumocystis carinil pneumonia was the most common opportunistic infection in these patients. Seven patients had symptoms of esophageal disease at the time of endoscopy, whereas three patients were asymptomatic. 1) Other Clinical Manifestations (IIIA4), 2) Diagnostic Indicators (IIIA3) 3A4-Tav-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Niedt, George W., MD; Schinella, Roger A., MD. Acquired Immunodeficiency Syndrome: Clinicopathologic Study of 56 Autopsies. Archives of Pathology and Laboratory Medicine, August 1985, Vol. 109: 727-734. Department of Pathology, Bellevue-New York University Medical Center, New York, New York. To better define the clinical and pathological aspects of AIDS, 56 patients with AIDS autopsied at the New York University Medical Center were studied. Several entities not previously described or emphasized in earlier series were uncovered: (1) three cases of necrotizing (tissue death) arteries with cytomegalovirus inclusions; (2) dissemination of Kaposi's sarcoma in 95% of cases; (3) unusual clinical and histologic presentations of Kaposi's sarcoma; and (4) a very high incidence of serious nonmycobacterial infections. In addition, previous autopsy stud- les have disagreed over such matters as the incidence of disseminated candidiasis, hemophagocytosis (destruction of red blood cells by another cell), and severe adrenal necroses in AIDS. All of these studies except one involved 10 to 12 cases each. The authors find that their study helps to resolve these disagreements. These authors reviewed the autopsy protocols and slides from 54 consecutive autopsies performed at New York University Medical Center on patients fulfilling the Centers for Disease Control criteria for AIDS. Complete autopsies were performed on 54 of 56 patients. Clinical infor- mation was obtained from autopsy protocols and clinical charts. The immediate cause of death was defined as the disease process(es) present in the organ system that clinically appeared to have failed. When more than one organ system seemed important in a patient's demise, both were included as causes of death. Of 56 patients, 47 were homosexual, 4 were intravenous drug abusers (2 of these were prisoners), | was Haitian, 2 were both homosexual and intravenous drug abusers, | had received multiple transfusions, and | had contact with a suspected carrier of AIDS. All of the patients studied were men. Forty-four were white, eight were black, and four were Hispanic. The average age was 40 years (range, 26 to 64 years). The vast majority of patients had histories of either hepatitis, syphilis, gonorrhea, giardiasis (a parasitic infection) or amebiasis. All had a progressive clinical course marked by multiple infections. Failure of either the respiratory or central nervous system or both predominated as the immediate cause of death. 1) Other Clinical Manifestations: at Autopsy (l[IA4), 2) Disease Stages (I1IC) 3A4-Nie-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Marcusen, David C., MD; Sooy, C. Daniel, MD. Otolaryngologic and Head and Neck Manisfestations of Acquired Immunodeficiency Syndrome (AIDS). Laryngoscope, April 1985, Vol. 95: 401-405. University of California School of Medicine, San Francisco, California. Patients with AIDS frequently present with head and neck signs and symptoms. Of patients with AIDS seen at the University of California, San Francisco, and its affiliated hospitals from 1980 to April 1984, 165 (41%) had head and neck manifestations on initial evaluation. Of that group, 58 (35%) had cutaneous, oral, and pharyngeal lesions of Kaposi's sarcoma (which would be less common in non-gay populations); 51 (31%) had oral, pharyngeal, esophogeal, or laryngeal candidiasis; 36 (22%) had chronic cough and shortness of breath; 13 (8%) had rapidly enlarging neck masses; and 7 (4%) had herpes simplex lesions. The authors state that with the increasing number of AIDS cases, it is important for the otolaryngologist to be aware of these presentations, and that early diagnosis is necessary both to reduce patient morbidity and to provide appropriate referrals if the otolaryngologist suspects a patient has AIDS. In the confirmed cases of AIDS involved in this study, the presenting and resulting symptoms and their relationship to otolaryngology and the head and neck were studied. Also determined were immune status at the time of diagnosis, treatment, special studies, and sexual orientation and other significant social history. A total of 399 AIDS cases were reviewed. - Patients were between 15 and 60 years of age. All had Kaposi's sarcoma, Pneumocystis carinii pneumonia, or another opportunistic infection which posed a significant health threat to the patient. 1) Other Clinical Manifestations (IlIA4), 2) Diagnostic Indicators (IIIA3), 3) Precursors of AIDS (IIIB) 3A4-Mar-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Wheat, L. Joseph, MD; Slama, Thomas G., MD; Zeckel, Michael L., MD. Histoplasmosis in the Acquired Immune Deficiency Syndrome. The American Journal of Medicine, February 1985, Vol. 78: 203-210. Wishard Memorial Hospital; Indianapolis Veterans Administration Hospital; Indiana University Medical Center; Indianapolis St. Vincent's Hospital; Methodist Hospital; Meridian Medical Group, Inc., Indianapolis, Indiana. This report describes the experience with disseminated histoplasmosis (a systemic fungal disease) in 7 of 15 patients with AIDS diagnosed in Indianapolis since 1981. Six of the seven had associated infections: candidiasis in three patients, and Pneumocystis carinii pneumonia, recurrent mucocutaneous (mucous membrane and skin) herpes simplex infection, and disseminated infection with an unidentified mycobacterium in one patient each. Clinical diseases suggested sepsis In four. Histoplasma fungemia occurred in five, but the diagnosis was first established by visualization of organisms in blood or bone marrow in three. Results of serologic tests were positive for Histoplasma in each. Three died before receiving 50 mg of amphotericin B (an antifungal drug), three had prompt improvement with amphotericin B, and one was treated with ketoconazole (another antifungal drug) to prevent dissemination. However, two of the three patients treated with amphotericin B relapsed after receiving 35 mg/kg, and the third died within a month after therapy. Disseminated histoplasmosis is a major opportunistic infection in patients from areas where AIDS is endemic. AIDS should be strongly considered in otherwise healthy persons with disseminated histoplasmosis, especially if risk factors for AIDS are present. Amphotericin B is not curative in these patients. This is a set of case reports of Indiana residents identified as having AIDS since 1981. Clinical and laboratory features of these patients are described. Seven of 15 Indiana residents with AIDS were studied; three were homosexual, two were intravenous drug abusers, one was a spouse of another patient with AIDS and disseminated histoplasmosis, and the seventh was a hemophiliac. Six had associated infections, and four had sepsis. 1) Other Clinical Manifestations: Histoplasmosis (II[A#%), 2) Treatments: Symptom Management (IVB) 3A4-Whe-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Pitchenik, Arthur E.; Rubinson, Howard A. The Radiographic Appearance of Tuberculosis in Patients with the Acquired Immune Deficiency Syndrome (AIDS) and Pre-AIDS. American Review of Respiratory Diseases, 1985, Vol. 131: 393-396. Department of Medicine, Pulmonary Division, Department of Radiology, University of Miami School of Medicine, Miami, Florida. This study evaluated the chest X-ray findings in 23 adult AIDS patients with culture-proven tuberculosis. The appearance of tuberculosis on X- rays was very different from the usual X-ray appearance of adult tuberculosis (abnormalities of the upper lung fields). In the AIDS patients, chest X-ray findings included lymph node enlargement in the region around the heart (59%), abnormalities in the middle and lower lung fields (29%), diffuse abnormalities throughout the lung fields (18%), and abnormalities in the upper lung zones (18%). Pulmonary infiltrates were absent in six patients (35% of cases); in four of these, there were lymph node abnormalities. Two patients (12%) had completely normal chest X-rays. Pulmonary cavitation, a common finding in adult tuberculosis, was absent among these AIDS patients. Six patients had Mycobacterium tuberculosis isolated only in cultures of samples taken from sites other than the lung. Three of these had lymph node enlargement in the area around the heart on chest X-ray. For 17 of the 23 patients, cultures of the sputum or special sputum samples obtained by bronchoscopy were positive for M. tuberculosis. The authors conclude that the chest X-ray findings for adult AIDS patients with tuberculosis are very different from those for adult patients with tuberculosis who do not have AIDS. This study consisted of retrospective case analysis of patients admitted to the Jackson Memorial Hospital, Miami, Florida, between 1 January 1980 and 30 June 1983 with AIDS and positive cultures for M. tuberculosis. oo Twenty-seven patients meeting the criteria for AIDS established by the Centers for Disease Control who were culture-positive for M. tuberculosis were included in the study (19 men, 4 women; age 21 to 49 years). Twenty-two patients were Haitian. Thirty Haitian patients who were culture-positive for M. tuberculosis (26 men, 4 women; age 16 to 53 years) were included as controls. 1) Other Clinical Manifestations (I[IA%), 2) Diagnostic Indicators (I[IA3) 3A4-Pit-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Vaziri, N.D., MD; Barbari, A., MD; Licorish, K., MD; Cesario, T., MD; Gupta, S., MD. Spectrum of Renal Abnormalities in Acquired Immune-Deficiency Syndrome. Journal of the National Medical Association, 1985, Vol. 77, No. 5: 369- 375. Divisions of Nephrology, Basic and Clinical Immunology, and Infectious Diseases, Department of Medicine, University of California, Irvine, California. This study compares kidney function in patients with AIDS, AIDS-related complex (ARC), and healthy control subjects to determine the spectrum of renal abnormalities in AIDS. Comparisons of clinical data from patients with AIDS, ARC patients, and healthy controls revealed that kidney failure occurred with considerable frequency among the AIDS patients, while kidney function was stable in the ARC patients studied. Five of these patients developed typical acute renal failure; four died, and one recovered renal function. Other clinical aspects were also compared, showing differences in frequency among AIDS patients and ARC patients. Study observations point to the prevalence and significance of renal and associated abnormalities in AIDS: proteinuria, hematuria, leukocyturia, bacteriuria (presence of protein, blood, white blood cells, and bacteria, respectively, in the urine), and urinary tract infections not related to venereal disease. Other disorders of fluids, electrolytes, acid-base balance, and calcium and phosphorus metabolism were common in AIDS patients and uncommon among ARC patients. Clinical findings from records of homosexual male patients with AIDS and ARC and for a control group of heterosexual men were compared. Immunologic and serologic tests were performed and results, with other clinical information, were used for comparisons. Data for 27 patients managed for AIDS or ARC at the University of California, Irvine, Medical Center were included in the study. All were homosexual men, 24 to 53 years old, some of whom had a recent history of recreational drug use. None had a history of chronic intravenous drug abuse. A control group of 15 normal heterosexual men was used for comparisons. 1) Other Clinical Manifestations: Kidney Complications (I[IA4) 3A4-Vaz-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Greenspan, Deborah; Conant, Marcus; Silverman, Sol, Jr.; Greenspan, John S.; Petersen, Vibeke; De Souza, Yvonne. Oral "Hairy" Leucoplakia in Male Homosexuals: Evidence of Association with Both Papillomavirus and a Herpes-Group Virus. The Lancet, 13 October 1984, Vol. 2, No. 8407: 831-834. Departments of Stomatology (Divisions of Oral Medicine and Oral Biology), Dermatology, and Pathology, Schools of Dentistry and Medicine, University of California, San Francisco, California. Hairy leukoplakia (usually seen as white sores of the tongue) appears to be a new entity so far found exclusively in the mouths of male homosexuals. There is evidence that many of the patients are immunosuppressed, that many have lymph node disease, and that a substantial proportion progress to AIDS. (Of 13 patients whose helper/suppressor T-cell ratios were assessed, ll had abnormally low ratios.) Hairy leukoplakia is similar to flat warts of the skin (caused by papillomavirus). There was evidence of papillomavirus core antigen in 77% of 30 biopsy specimens, but no papillomaviruses were detected by electron microscopy in samples from six randomly selected patients. In five of these six patients there was evidence of a herpes-type virus. Pneumocystis carinii pneumonia developed in 8 of 37 patients in a 33- month period. Between October 1981 and July 1984, all patients gave a detailed medical and social history in response to standard questionnaires and had complete physical and oral exams. When white oral sores were found, tests for Candida were performed. Biopsy specimens were obtained from 30 of the 37 patients for routine microscopic evaluation. Studies were done on blood specimens to determine immune system status, including measurement of T-cell subsets with OKT4 and OKT8 monoclonal antibodies. Tests for papillomavirus antigen within the sore with rabbit antiserum were also performed. Thirty-seven homosexual men referred to the oral medicine clinic at the University of California, San Francisco, who suffered from white lesions of the tongue (hairy leukoplakia) were studied. 1) Other Clinical Manifestations: Oral Symptoms (I[IA%4), 2) Populations: Homosexuals (IA1), Precursors of AIDS (IIIB) 3A4-Gre-9 Author(s): Title: Source: Institution: Findings: Ziegler, John L., MD; Beckstead, Jay A., MD; Volberding, Paul A., MD; Abrams, Donald [., MD; Levine, Alexandra M., MD; Lukes, Robert J., MD; Gill, Parkash S., MD; Burkes, Ronald L., MD; Meyer, Paul R., MD; Metroka, Craig E., MD, PhD; Mouradian, Janet, MD; Moore, Anne, MD; Riggs, Shirley A., MD; Butler, James J., MD; Cabanillas, Fernando C., MD; Hersh, Evan, MD; Newell, Guy R., MD; Laubenstein, Linda J., MD; Knowles, Daniel, MD; Odajnyk, Chrystia, MD; Raphael, Bruce, MD; Koziner, Benjamin, MD; Urmacher, Carlos, MD; Clarkson, Bayard D., MD. Non-Hodgkin's Lymphoma in 90 Homosexual Men: Relation to Generalized Lymphadenopathy and the Acquired Immunodeficiency Syndrome. The New England Journal of Medicine, 30 August 1984, Vol. 311, No. 9: 565-570. Department of Medicine, Veterans Administration Medical Center and University of California, San Francisco, California; Adult Hematologic Neoplasia Service, Kenneth Norris, Jr., Cancer Hospital, University of Southern California, Los Angeles, California; Division of Hematology- Oncology, New York Hospital-Cornell Medical Center, New York, New York; Department of Hematology, University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Center, Houston, Texas; Hematology-Oncology Service, Rita & Stanley Kaplan Cancer Center, New York University Medical Center, New York, New York; Hematol- ogy/Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York. This study chronicled the histologic and clinical aspects of non-Hodgkin's lymphoma in a group of homosexual men. The results indicate that non- Hodgkin's lymphoma in members of an AIDS risk group is a serious manifestation of AIDS and AIDS-related complex. Of the 90 subjects, 62% had high-grade (aggressive) subtypes of lymphoma, 29% had intermediate-grade subtypes, and 7% had low-grade subtypes. Histologic subtypes and malignant-cell phenotypes were consistent with a B-cell origin. All but two men had lymphoma outside the lymph nodes; the most common sites were the central nervous system, bone marrow, and skin or mucous membrane. At diagnosis of non-Hodgkin's lymphoma, 12 men were asymptomatic: 4 have died, | is alive but ill, and 7 (58%) are alive and asymptomatic. Thirty-three men had generalized lymphadenopathy before the non- Hodgkin's lymphoma diagnosis: 19 have died, 7 are alive but ill, and 7 (21%) are alive and without symptoms. AIDS developed in 14 of these 33 lymphadenopathy patients (12 with opportunistic infections, 2 with Kaposi's sarcoma). Twenty-one men had AIDS before the non-Hodgkin's lymphoma diagnosis: 15 have died, 4 are alive but ill, and only 2 (9%) are alive and without symptoms. Mortality rates analyzed by histologic grade were higher than those reported for other patient populations. Of 66 evaluable men, 35 (53%) had complete responses to chemotherapy or X-ray therapy or both; during the study, 19 (54%) of these relapsed. 3A4-Zie-10 Method: Sample Size: Policy Keys: This clinical study identified all known homosexual men at participating institutions in whom non-Hodgkin's lymphoma had developed between January 1980 and December 1983. All histologic material was reviewed by a hematologist at a participating institution and classified according to the Non-Hodgkin's Lymphoma Pathological Classification Project. Clinical data included age, prodromal manifestations, clinical stage (Ann Arbor criteria), disease sites, initial treatment and response, and survival from time of treatment to death or to 31 December 1983. The criteria used to diagnose lymphadenopathy and AIDS conformed to those of the Centers for Disease Control (CDC). A total of 90 homosexual men with non-Hodgkin's lymphoma (median age, 37; range, 20 to 61, identical with that of AIDS cases reported by the CDC) were studied: 19 from the University of Southern California Norris Cancer Hospital, Los Angeles; 18 from New York Hospital-Cornell Medical Center, New York; 17 from University of Southern California, San Francisco; 14 from M. D. Anderson Hospital and Tumor Institute, Houston; 12 from New York University Medical Center, New York; and 10 from Memorial Sloan-Kettering Cancer Institute, New York. 1) Other Clinical Manifestations: Non-Hodgkin's Lymphoma (Il1IA4%), 2) Disease Stages (IIIC), 3) Treatment: Symptom Management (IVB) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Rosenberg, Richard A., MD; Schneider, Kenneth L., MD; Cohen, Noel L., MD. Head and Neck Presentations of Acquired Immunodeficiency Syndrome. Laryngoscope, May 1984, Vol. 94: 642-646. Department of Otolaryngology, New York University Medical Center, New York, New York. Charts of 72 patients admitted to a New York hospital with a diagnosis of AIDS were reviewed. AIDS patients present with a wide variety of symptoms, some of which are manifestations of secondary infections. Fifty-four patients were admitted with a low-grade persistent fever lasting several months. Thirty-seven patients presented with a cough, usually with only a scant amount of yellow-green sputum. Thirty-two patients experienced weight loss, and seven patients were anorexic. Dyspnea (shortness of breath) was noted in 18 patients, usually after exertion, and 34 patients complained of general weakness or fatigue. Four presenting signs were present in more than 95% of the patients: diffuse lymphadenopathy (52), oral and facial lesions consistent with the Kaposi's sarcoma (29), white oral lesions (28), and anergy (diminished sensitivity to antigens) (26), especially for mumps virus, Candida, and tuberculosis. Four patients were found to have cotton-wool spots on eye exams. Anemia was a common finding, and the death rate in-hospital was 19 of 72 (26%). Lab findings also included leukopenia, increased erythrocyte sedimentation rate, and thrombocytopenia. The authors present the frequency and type of presenting signs and symptoms to alert the otolaryngologic community. The charts of patients with a diagnosis of AIDS were reviewed. All the data for the patients' symptoms and signs were taken from their admission histories and physical examinations. All lab values were from admission blood tests. Signs, symptoms, and lab data recorded during hospitalization were not reported, as they might have reflected responses to or effects of therapeutic intervention. Mortality figures were based only on recorded (in-hospital) deaths and probably underestimated the true figures, according to these authors. Charts of 72 patients admitted to New York University Medical Center with a diagnosis of AIDS were reviewed. These patients had been admitted between December 1981 and June 1983. Ages ranged from 20 to 65 years (mean, 39 years). All 72 patients were male. There were 64 Caucasians, 6 blacks, and 2 Hispanic patients. Sixty-one of the patients were homosexual, 3 were bisexual, 4 were heterosexual, and 4 were of unknown sexual history. Ten patients had a history of intravenous drug abuse. Nearly all the patients in this study had a history of multiple past infections, including hepatitis, infectious mononucleosis, syphilis, gonorrhea, oral thrush, and herpes. Thirty-seven had Kaposi's sarcoma, 32 had Pneumocystis carinii pneumonia, 15 had cytomegalovirus in the liver, lungs, or brain, eight had Legionella, six had Cryptococcus in the brain or meninges, four had toxoplasmosis, three had Mycobacterium tuberculosis (tuberculosis), and three had Mycobacterium avium- intracellulare. 3A4-Ros-11 Policy Keys: 1) Other Clinical Manifestations (II[IA%) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Rao, T.K. Sreepada, MD; Filippone, Edward J., MD; Nicastri, Anthony D., MD; Landesman, Sheldon H., MD; Frank, Elliot, MD; Chen, C.K., MD; Friedman, Eli A., MD. Associated Focal and Segmental Glomerulosclerosis in the Acquired Immunodeficiency Syndrome. The New England Journal of Medicine, 15 March 1984, Vol. 310, No. 11: 669-673. Departments of Medicine and Pathology, Kings County Hospital and Downstate Medical Center, State University of New York, Brooklyn, New York. This study focused on kidney disease in AIDS patients. Results of the evaluation of 11 AIDS patients indicate that focal and segmental glomerulosclerosis (scarring or deposits within a vital part of the kidney) may be associated with AIDS and that rapid deterioration to uremia may characterize this renal disease. For 10 patients the time to severe uremia was 8 to 16 weeks. This progression had not been observed in other AIDS patients studied previously by the authors. Of 11 patients, 10 died and | (a black Haitian woman who progressed to severe uremia in 8 weeks) is on dialysis. Biopsy and autopsy tests showed focal and segmental glomerulosclerosis in 10 patients. In the llth patient (who did not progress to severe uremia before death), renal biopsy revealed an increase in mesangial matrix and cells, with deposition of immunoglobu- lin G and serum complement C3, consistent with a mild immune complex glomerulonephritis, and severe interstitial nephritis. The authors conclude that focal and segmental glomerulosclerosis may be associated with AIDS and suggest that rapid deterioration to uremia may charac- terize this renal disease. Kidney tissue was examined by biopsy for eight patients and at autopsy for three patients. This renal tissue was examined by light, immuno- fluorescence, and electron microscopy. Eleven patients of a total of 92 AIDS patients who were seen at Kings County Hospital and Downstate Medical Center in Brooklyn, New York, between 1981 and September 1983 were studied. Nine AIDS patients with nephrotic syndrome (more than 3.5 g of protein excreted in the urine per 24 hours) included one male Haitian, one female Haitian, one black female intravenous (I.V.) heroin addict, three black male [.V. heroin addicts, one black male homosexual I[.V. heroin addict, and two black male homosexuals. Two other AIDS patients with uremia with lesser amounts of protein in the urine included one male Haitian and one black woman. All Haitian subjects were living in the U.S. Six patients had no kidney disease risk factors. The age range of patients was 22 to 26 years. 1) Other Clinical Manifestations: Kidney Disease (I[IA4) 3A4-Rao-12 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Freeman, William R., MD; Lerner, Chester W., MD; Mines, Jonathan A., MD; Lash, Roger S., MD; Nadel, Alfred J., MD; Starr, Michael B., MD; Tapper, Michael L., MD. A Prospective Study of the Ophthalmologic Findings in the Acquired Immune Deficiency Syndrome. American Journal of Ophthalmology, February 1984, Vol. 97, No. 2: 133- 142. Departments of Ophthalmology (Freeman, Mines, Lash, Nadel, Starr) and Medicine (Section of Infectious Diseases) (Lerner, Tapper), Lenox Hill Hospital, New York, New York. Twenty-six AIDS patients were evaluated ophthalmologically; 19 patients showed significant eye abnormalities. Of these, two (8%) had retinal hemorrhages; seven (27%) had cotton-wool spots; three (15%) had cytomegalovirus retinitis; and one (5%) had acute retinal necrosis. The last two disorders were progressive and destructive. Other symptoms included cranial nerve palsies and Kaposi's sarcoma of the eye socket. Hemorrhages and cotton-wool spots appeared and disappeared spontaneously. These results highlight the importance of examining any AIDS patient several times. The study produced significant ophthalmological findings for 19 of 26 (73%) patients because 20 patients were examined two to eight times. If each patient had been examined only once, the authors would have concluded that as few as eight (319%) had ophthalmological disorders. For this prospective study, all patients were examined within several weeks of admission for AIDS and from one to eight times during the study. Six patients were examined only once; of these, one died, and the others are in other institutions or other cities or were lost to follow-up. Twenty patients underwent several ophthalmologic exams, usually including color fundus photography to document normal and abnormal findings. Photographs were taken with a variable-angle fundus camera or with a portable camera; all color photos were taken on Kodachrome 64 film. A cohort of AIDS patients at Lenox Hill Hospital, New York City, admitted between 1982 (month unidentified) and April 1983 were studied: 24 homosexual males (1 black, 3 Hispanic, 19 white, and | white intravenous (I.V.) drug user), one Hispanic female I.V. drug user, and one Hispanic heterosexual male I.V. drug user. Their ages ranged from 24 to 55 years (average, 36). 1) Other Clinical Manifestations (I[IA4), 2) Disease Stages (IIIC) 3A4-Fre-13 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Khadem, May, MD; Kalish, Steve B., MD; Goldsmith, JoAnne, MD; Fetkenhour, Carl, MD; O'Grady, Richard B., MD; Phair, John P., MD; Chrobak, Martin. Ophthalmologic Findings in Acquired Immune Deficiency Syndrome (AIDS). Archives of Ophthalmology, February 1984, Vol. 102, No. 2: 201-206. Department of Ophthalmology (Khadem, Fetkenhour, O'Grady, Chrobak) and Section of Infectious Disease, Department of Medicine (Kalish, Goldsmith, Phair), Northwestern University Medical School, Chicago, Illinois. To further define the incidence and prognosis of eye lesions in patients with AIDS, #41 homosexually active men with ophthalmologic and immunologic abnormalities were evaluated prospectively. Four of eight with AIDS had eye abnormalities, including cotton-wool spots, retinal hemorrhages, cytomegalovirus infection, retinitis and conjunctivitis due to cytomegalovirus, and keratoconjunctivitis sicca (inflammation of the eyeball surface due to deficiency of tears). The other four patients with AIDS and 33 homosexual male controls had normal eye exams. Patients with AIDS and abnormal eye findings had a notably lower total leukocyte count, absolute lymphocyte count, percentage of helper T cells, helper/suppressor T-cell ratio, hematocrit level, and platelet count than AIDS patients with normal eye exam results and controls. All AIDS patients with abnormal eye exams died; the four AIDS patients with normal eye exams remain alive. These observations suggest, according to the authors, that ophthalmologic abnormalities are common in patients with AIDS, are associated with severe immunoregulatory abnormalities, and carry a poor prognosis. This prospective study evaluated ophthalmologic findings in individuals at high risk for AIDS. Each participant completed a detailed questionnaire on sexual practices and drug use. These forms were reviewed by a doctor. Blood samples were collected and lymphocytes were separated; T lymphocytes, T-cell subsets, and B lymphocytes were identified. Other routine blood tests were also done, such as complete blood cell counts. Blood immunoglobulin levels were determined. Skin hypersensitivity testing for Candida, Trichophyton (a fungus), histoplasmin, and mumps virus was done. Viral cultures were also performed. Eye exams included tests of visual acuity, pupils, and intraocular pressure. Biomicroscopy and indirect ophthalmoscopy were done as well. Differences between patients were analyzed statistically. Forty-one homosexually active men were studied who were randomly selected from 200 individuals who were participating in an ongoing pro- spective study of homosexually active men at Northwestern University Medical School. Eight individuals had Kaposi's sarcoma, Pneumocystis carinii pneumonia, and/or other opportunistic infections (AIDS patients), and the remaining 33 subjects were recruited from a previous hepatitis B vaccine trial, were referred from private physicians or sexually transmitted disease clinics, or volunteered for the study. These 33 3A4-Kha-14 Policy Keys: subjects served as controls; 18 of them were considered symptomatic (having AIDS-related symptoms). None of this group had evidence of malignancy or were receiving immunosuppressive therapy. Fifteen con- trols were asymptomatic. 1) Other Clinical Manifestations: Ophthamologic (IIIA4), 2) Disease Stages (LIC), 3) Immunological Aspects (IIE), 4) Populations: Homosexuals (IA 1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Gardenswartz, M.H.; Lerner, C.W., Seligson, G.R.; Zabetakis, P.M.; Rotterdam, H.; Tapper, M.L.; Michelis, M.F.; Bruno, M.S. Renal Disease in Patients with AIDS: a Clinicopathologic Study. Clinical Nephrology, 1984, Vol. 21, No. 4: 197-204. Sections of Nephrology and Infectious Diseases, Department of Medicine, and Department of Pathology, Lenox Hill Hospital, New York, New York. To determine the nature and frequency of renal (kidney) disorders in AIDS, the authors reviewed the records of 32 patients seen over a 22- month period. Group [ (13 patients) had renal abnormalities, including proteinuria in 12 patients and kidney failure in I. Glomerular histologic lesions included various degrees of degeneration, hardening of tissue, proliferation of the cells, and infection of the glomerular tissue itself. Nonglomerular hisologic lesions of the kidney included acute degeneration, calcified tissue, various types of infection, and, in one case, cancer. Nine of these 13 patients developed renal insufficiency, and four of them required dialysis. Eleven of the 13 (85%) patients had died by the end of the study period, which is a significantly worse percentage in the short term than for AIDS patients without renal problems. The patients in group I had a higher incidence of oral and esophogeal candidiasis, other fungal infections, and Mycobacterium avium-intracellulare infection. These patients also experienced more clinical shock than their group II (without proteinuria or renal failure) counterparts, and had more exposure to nephrotoxic antibiotics. These authors concluded that in patients with AIDS, kidney problems may be due to immune, hemodynamic (movement of the blood), infectious, and neoplastic disorders. In this retrospective study, 32 patients with AIDS from a university- affiliated hospital were chosen and placed into two groups according to whether or not renal disease could be established. This information was ascertained by their private physicians by clinical evaluation, cultures, serological tests, urine analysis, x-rays, and biopsies. Thirteen patients with evidence of large amounts of protein in their urine and/or renal failure were included in group I. The remaining patients, without renal failure or proteinuria, composed group Il. The incidence of infection and Kaposi's sarcoma in group II was compared with that in group I. Thirty-two patients with AIDS who had been hospitalized at a university- affiliated hospital between | March 1981 and 31 December 1982 were included in this sample. ) Other Clinical Manifestations (IIIA4) 3A4-Gar-15 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lozada, Francina, DDS, MS; Silverman, Sol Jr., MA, DDS; Migliorati, Cesar A., DDS; Conant, Marcus A., MD; Volberding, Paul A., MD. Oral Manifestations of Tumor and Opportunistic Infections in the Acquired Immunodeficiency Syndrome (AIDS): Findings in 53 Homosexual Men with Kaposi's Sarcoma. Oral Surgery, November 1983, Vol. 56, No. 5: 491-494. Division of Oral Medicine, School of Dentistry (Lozada, Silverman, Migliorati), Departments of Dermatology and Medicine, School of Medicine (Conant, Volberding), University of California, San Francisco, California. This report describes the oral findings for a group of male homosexual AIDS patients to alert clinicians to the frequency and appearance of oral lesions, possible transmission risks, and management approaches. Of 53 homosexual men with Kaposi's sarcoma (KS) who were given an oral examination, 27 (51%) had biopsy-proved oral KS. Twenty-four of these lesions occurred in the palate, which was by far the most common site. Nine patients had multiple oral sites, and all but two had KS occurring in skin. Past or present infections with cytomegalovirus, hepatitis, vener- eal disease, or gastrointestinal microorganisms occurred in more than 70%. Oral candidiasis was confirmed in 57%. Drug use was frequent, marijuana smoking being the most common. Oral KS should be suspected whenever bluish discolorations or lesions of the vascular type are observed. The authors urge precautions in dental care, including the use of gloves, eyeglasses, and masks, similar to those recommended for the management of patients with hepatitis B. Between August 1981 and May 1983 all homosexual men with KS seen consecutively in the oral medicine clinic at the University of California, San Francisco, were given an oral examination. Each patient's history was reviewed for opportunistic infections, drug use, and social habits. All lesions observed and suspected of being tumor or infection were biopsied or appropriately cultured. Fifty-three San Francisco homosexual men were examined; their ages ranged from 21 to 63 years (mean, 38). Each patient had been previously evaluated for AIDS in the KS clinic at the School of Medicine, University of California, San Francisco. All patients had biopsy-proved KS as well as other opportunistic infections. 1) Other Clinical Manifestations: Oral Symptoms (IlIA4), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIAl), 3) Infection Control in Occupational Settings (VC), 4) Cofactors: Other Infections, Drug Use (IC3,2), 5) Populations: Homosexuals (IA 1) 3A4-Loz-16 [II. Characteristics of Disease B. Precursors of AIDS and AIDS-Related Complex Author(s): Title: Source: Institution: Findings: Method: Tenner-Racz, Klara, MD; Racz, P., MD; Bofill, Margarita, PhD; Schulz- Meyer, Anke; Dietrich, M., MD; Kern, P., MD; Weber, J., MBBS, MRCP; Pinching, A.J., BM, BCh, MA, DPhil, MRCP; Veronese-DiMarzo, Fulvia, PhD; Popovic, M., MD; Klatzmann, D., MD, DSc; Gluckman, J.C., MD; Janossy, G., MD, PhD, MRCPath, DSc. HTLV-III/LAV Viral Antigens in Lymph Nodes of Homosexual Men with Persistent Generalized Lymphadenopathy and AIDS. American Journal of Pathology, April 1986, Vol. 123, No. 1: 9-15. Department of Haematology, Allegemeines Krankenhaus St. Georg, Hamburg; Institute for Tropical Diseases, Hamburg, Federal Republic of Germany; Department of Immunology, Royal Free Hospital School of Medicine, London; Department of Immunology, St. Mary's Hospital Medical School, London, England; Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland; Laboratoire d'Immunologie, Nephrologique et Transplantation, UFR Pitie-Salpetriere, Paris, France. This study considers the micropathology of the lymph node in 32 patients seropositive for antibody to human T-cell lymphotropic virus type [lI/lymphadenopathy-associated virus (HTLV-III/LAV). Immunohisto- logical analysis of lymph node structure in 28 patients with persistent generalized lymphadenopathy (PGL), | patient with prodromal AIDS, and 3 patients with AIDS and Kaposi's sarcoma revealed the deposition of AlIDS-associated viral (AV) antigen in 30 of these patients. No AV antigen was demonstrable in normal tonsillar tissue, or in lymph node tissue from 20 patients with lymphoproliferative syndromes other than those above. Fine ultrastructural analysis revealed the presence, in 11 of these patients with lymphatic AV antigen, of typical viral particles. These particles could be localized to the surface of follicular dendritic (FD) cells, which are postulated to play a role in antigenic presentation (the process of antigenic processing necessary for lymphocyte activation). The presence of retroviral particles on, and possibly in, FD cells suggests that these cells may in fact serve as a reservoir for viral replication. The authors suggest that this may explain the characteristic lymph node findings in PGL and prodromal AIDS. They further suggest that the ability to demons-rate the presence of AV antigen in the lymph nodes of patients with AV-associated lymph node disease, and the characteristic ansence of AV antigen in lymph node disorders of other etiology, offers potential diagnostic and prognostic insight for patients with unexplained lymph node enlargement. Lymph node samples were obtained from all patients and examined. Eleven lymph nodes known to contain typical retrovirus particles were studied by electron microscopy and stored for 9 to 24 months before the study. Twenty-one lymph node samples were taken from 2 to 8 months before the study. Testing included monoclonal antibodies, antisera, histochemistry, and immunofluorescence. 3B-Ten-1 Sample Size: Policy Keys: Lymph node samples were obtained from 32 male homosexual patients (age range, 21 to 50 years) from London and Hamburg, 28 lymphadenopathy patients, 1 AIDS patient, and 3 patients with AIDS and Kaposi's sarcoma. All patients were initially seropositive for HTLV- [II[/LAV, although one was negative at the time of biopsy. Samples from 20 healthy control subjects (10 pediatric tonsils and 10 adult lymph nodes) were also used. 1) Precursors of AIDS (IIB), 2) Diagnostic Indicators (IIIA 3) Author(s): Title: Source: Institution: Findings: Method: Sample: Policy Keys: Sandor, Earl V., MD; Millman, Arthur, MD; Croxson, T. Scott, MD; Mildvan, Donna, MD. Herpes Zoster Ophthalmicus in Patients at Risk for the Acquired Immune Deficiency Syndrome (AIDS). American Journal of Ophthalmology, February 1986, Vol. 101, No. 2: 153- 155. Department of Ophthalmology (Sandor, Millman), New York Eye & Ear Infirmary; Departments of Pathology (Croxson) and Medicine (Mildvan), Beth Israel Medical Center and Mount Sinai School of Medicine, New York, New York. Fifty-four consecutive cases of herpes zoster ophthalmicus (shingles affecting the ophthalmic branch of the trigeminal nerve) were studied prospectively over a 2-year period. This condition occurred with frequent complications in a subgroup of adults distinguished by their young age, presence of AIDS risk factors, and alterations in T-cell ratios. During the 2-year study, 21% of patients from the AIDS risk subgroup developed AIDS, with a 14% mortality rate. Herpes zoster ophthalmicus in AIDS risk group members appeared to be an early clinical marker for the immune deficiency induced by the AIDS retrovirus. For this 2-year prospective investigation, patients were given a complete ophthalmologic examination, and a detailed history, including information about sexual behavior, past infectious diseases, and intravenous drug use, was obtained. Patients were recalled for complete ophthalmic and general physical examinations with laboratory studies at least 2 months after the initial visit. Immunologic and blood tests were performed. Findings were compared by age and AIDS risk status. Fifty-four consecutive patients, 33 males and 21 females, seen at the New York Eye and Ear Infirmary with herpes zoster ophthalmicus were studied. Patients were divided into groups based on age and AIDS risk status. Group | included 23 patients ranging in age from 15 to 44 years (median, 34 years), and group 2 included 31 patients ranging in age from 45 to 86 years (median, 65). Of group | patients, 14 (61%) belonged to a group at risk for the development of AIDS. Eight were sexually active homosexuals and six were intravenous drug users. In contrast, none of the group 2 patients belonged to these risk groups. 1) Precursors of AIDS (IIIB), 2) Other Clinical Manifestations (I[1A4%) 3B-San-2 Author(s): Title: Source: Institution: Findings: Method: Murray, Henry W., MD; Hillman, Janice K., MD; Rubin, Berish Y., PhD; Kelly, Catherine D., BA; Jacobs, Jonathan L., MD; Tyler, Lisa W., BA; Donelly, Daria M., BA; Carriero, Susan M., BS; Godbold, James H., PhD; Roberts, Richard B., MD. Patients at Risk for AIDS-Related Opportunistic Infections: Clinical Manifestations and Impaired Gamma Interferon Production. The New England Journal of Medicine, 12 December 1985, Vol. 313, No, 24: 1504-1510. Divisions of Infectious Diseases and Immunology, Department of Medicine, Cornell University Medical College; New York Blood Center; Biostatistics Laboratory of Memorial Sloan-Kettering Cancer Center, New York. Patients at risk for AIDS were studied to determine whether those at risk for AIDS-related opportunistic infections could be identified prospectively, and to test the hypothesis that persons with the AIDS prodrome (ARC) who had the immunophenotype of fully established AIDS (i.e., no antigen-induced production of gamma interferon in vitro) are at immediate risk for the development of AIDS-related opportunistic infections. Because patients with the AIDS prodrome who have clinical manifes- tations other than or in addition to lymphadenopathy appear to be at greater risk for AIDS, patients were divided into two groups on the basis of their clinical findings. During the follow-up period, none of the 38 patients in group I (lymphadenopathy alone) developed infections; of group II patients (lymphadenopathy and one or more clinical manifesta- tions), only 1 of 15 patients with previous herpes zoster (shingles) infection developed infections. However, 13 of 28 (46%) patients with lymphadenopathy accompanied by oral candidiasis, constitutional symptoms, or both had opportunistic infections within the follow-up period. Among the results of various T-cell assays, only antigen-stimu- lated lymphocyte proliferation and gamma interferon generation, which were absent or barely measurable in those in whom AIDS ultimately developed, were of prognostic value. (T cells from 15 patients, 11 of whom had constitutional symptoms or oral candidiasis, failed to generate antigen-induced gamma interferon; infections developed in 67% of these 15 within an average of 8.2 months.) Study results indicate that patients with ARC who are at risk for opportunistic infections within a year can be identified by correlating clinical manifestations with antigen-stimulated T-cell responses -- in particular, the production of gamma interferon. This was a prospective study of 81 men with unexplained generalized lymphadenopathy to determine whether those at risk for AIDS-related opportunistic infections could be identified. Immunological testing was performed at the time of enrollment and during a follow-up period of 8 to 18 months. Generalized lymphadenopathy was defined as two or more enlarged lymph nodes outside the groin for at least 3 months. T-cell 3B-Mur-3 Sample Size: Policy Keys: subpopulations were identified by indirect immunofluorescence with OKT3, OKT4, and OKT8 monoclonal antibodies. Antibody to HTLV-III was measured by enzyme-linked immunosorbent assay. Skin sensitivity tests used standard preparations of Candida, mumps virus, Trichophyton (pathogenic fungus), tetanus toxoid, and purified-protein derivative antigens. The study included 81 of 85 men screened at a hospital for possible AIDS and found to have unexplained generalized lymphadenopathy between April 1983 and June 1984. Seventy-nine were homosexual, and two were narcotic drug abusers. Four of the 85 patients in whom an opportunistic infection developed within the first 12 weeks of testing were omitted from the analysis to reduce the likelihood that patients with unrecog- nized AIDS might have inadvertently been enrolled. At the time of enrollment and testing, 38 patients had lymphadenopathy alone and 43 had lymphadenopathy accompanied by herpes zoster, thrush, or constitutional symptoms. Sixty-nine of 76 patients (91%) were sero- positive for HTLV-II, and 76 of 79 (96%) had abnormal helper/suppressor T-cell ratios. 1) Precursors of AIDS (IIIB), 2) Disease Stages (IIIC), 3) Immunological Aspects (IIE) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Fishbein, Daniel B., MD; Kaplan, Jonathan E., MD; Spira, Thomas J., MD; Miller, Bess, MD; Schonberger, Lawrence B., MD; Pinsky, Paul F., MPH; Getchell, Jane P., DrPH; Kalyanaraman, Vaniambabi S., PhD; Braude, James S., MD. Unexplained Lymphadenopathy in Homosexual Men: A Longitudinal Study. Journal of the American Medical Association, 16 August 1985, Vol. 254, No. 7: 930-935. Divisions of Viral Diseases (Fishbein, Kaplan, Miller, Schonberger, Getchell, Kalyanaraman) and Host Factors (Spira), Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. In January 1982, the Centers for Disease Control began a prospective study of unexplained generalized lymphadenopathy in 78 homosexual or bisexual men. As of | August 1984, the median time since the onset of lymphadenopathy was 29.5 months (range, 8 to 62 months). Five of the 78 (6%) patients were diagnosed with AIDS 5, 8, 16, 17, and 25 months after the onset of lymphadenopathy. Antibodies to human T-cell lymphotropic virus type [lI/lymphadenopathy-associated virus (HTLV- [II[/LAV) were present in 75 (96%) of the patients at the initial visit. At the time of the initial visit, patients who subsequently developed AIDS had a number of laboratory values that distinguished them from patients who had not so far developed AIDS. These measures included lower helper T-cell counts, hematocrits, lymphocyte counts, and pokeweed mitogen stimulation ratios. These patients were more likely to report severe symptoms. Measures that did not distinguish between patients who developed AIDS and those who did not included (among others) the number of different sexual partners in the 2 years previous to developing lymphadenopathy syndrome, the number of episodes of passive oral or rectal intercourse during that time, the number of sexually transmitted infections, and the use of specific recreational drugs (such as nitrites). Except for the patients who developed AIDS, follow-up visits showed little change in the initial laboratory and clinical findings of this cohort. Patients were interviewed about the date of onset of lymphadenopathy and specific symptoms and signs. An index of severity of symptoms was defined (from | = no symptoms to 4 = severe symptoms). A history of sexual practices, sexually transmitted infections, and drug use was obtained. Each patient had a complete hematologic and immunologic evaluation performed at each visit, including complete blood cell count, differential cell count, and platelet count. Immunologic studies included enumeration of lymphocyte subsets, skin response to mitogen stimula- tion, and measurement of immunoglobulins, beta-2 microglobulin, and circulating immune complexes. Absolute numbers of T cells, helper T cells, and suppressor T cells were measured with monoclonal antibodies (OKT3, OKT4, and OKT3). Homosexual and bisexual men in Atlanta with lymphadenopathy in at least two sites outside the groin were referred between January 1982 and August 1983. The 78 patients enrolled in the study fulfilled the following 3B-Fis-4 criteria: (1) lymphadenopathy present for 3 months, (2) no concurrent ill- ness to account for the lymphadenopathy, (3) AIDS not yet diagnosed, and (4) agreement to participate. Policy Keys: 1) Precursors of AIDS (IIIB), 2) Disease Stages (IIIC), 3) Populations: Homosexuals (IA 1), 4) Immunological Aspects (IIIE) Author(s): Title: Source: Institution: Findings: Method: Boyko, William J., MD, FRCPC; Schechter, Martin T., MD, MSc, PhD; Jeffries, Eric, MB, MPH, FRCPC; Douglas, Bruce, MD, FRCPC; Maynard, Michael, MD; O'Shaughnessy, Michael, PhD. The Vancouver Lymphadenopathy-AIDS Study: 3. Relation of HTLV-II Seropositivity, Immune Status and Lymphadenopathy. Canadian Medical Association Journal, 1 July 1985, Vol. 133: 28-32. St. Paul's Hospital and the University of British Columbia, Vancouver (Boyko, Schechter, Jeffries, Douglas, Maynard); Division of Viral Studies, Laboratory Centre for Disease Control, Department of National Health and Welfare, Ottawa, Ontario, Canada (O'Shaughnessy). This study examined the interrelation of human T-cell lymphotropic virus type III (HTLV-II) seropositivity, abnormality of immune function, and lymphadenopathy. On the whole, 136 of 394 (34%) of homosexual males in the sample were seropositive. When the subjects were grouped by clinical symptoms, HTLV-III antibody was detected in 61% of the subset of patients with persistent generalized lymphadenopathy (PGL), in 32% of those with slight or nonpersistent lymph node enlargement (an intermediate group) and in 18% of controls, who had no lymph node enlargement. The degree of abnormal immune function, as shown by abnormalities in immunoglobulin levels, immune complex activity, and T-lymphocyte subsets, was correlated with the extent of lymphadenopathy. A similar pattern of immunologic abnormality was associated with seropositivity for HTLV-II antibody. However, HTLV-III seropositivity was the major determinant of immune function after adjustment for lymph node status. Among the 188 who were tested on two occasions, the approximate annual seroconversion rate was 15% during the study period. Although several seropositive subjects were identified who were free of clinical disease and immunologic abnormality, the authors suggest that the immune dysfunction seen in patients with lymphadenopathy in this study was due for the most part to the high prevalence of HTLV-II seropositivity in these populations. The participants completed a self-administered questionnaire and underwent a complete physical examination, including measurement of lymph node size and laboratory testing, on two occasions at least 3 months apart. PGL was defined as the presence of lymph nodes greater than | cm in diameter at two or more sites outside the groin for more than 3 months. Subjects with these symptoms formed the PGL group. The other two groups consisted of subjects with slight or nonpersistent lymph node enlargement, and those with no lymph node enlargement(controls). Blood serum samples were tested for HTLV-II antibody by enzyme-linked immunosorbent assay. Negative samples were also tested by Western blot. Lymphocyte subsets and immune complex activity were also determined. 3B-Boy-5 Sample Size: Policy Keys: From November 1982 to February 1984, 394 homosexual men were recruited from six general practices in central Vancouver. Of these, 77 were in the PGL group, 110 were in the intermediate group, and 207 were controls. 1) Precursors of AIDS (IIIB), 2) Incubation Period and Disease Stages (ITIC), 3) Populations: Homosexuals (IAL) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Schechter, Martin T., MD, MSc, PhD; Boyko, William J., MD, FRCPC; Jeffries, Eric, MD, MPH, FRCPC; Willoughby, Brian, MD, CCFP; Nitz, Rod, MD; Constance, Peter, MB, BS. The Vancouver Lymphadenopathy-AIDS Study: |. Persistent Generalized Lymphadenopathy. Canadian Medical Association Journal, 1 June 1985, Vol. 132: 1273-1279. St. Paul's Hospital and the University of British Columbia, Vancouver, Canada. In this ongoing prospective study of over 700 homosexual men in Vancouver, a case-control evaluation was conducted of risk factors for persistent generalized lymphadenopathy in homosexual men. Of the 519 patients who had completed two visits by February 1984, 126 (24%) were found to have persistent generalized lymphadenopathy, and two controls without lymphadenopathy were matched with each case. More than 100 lifetime male sexual partners, frequent receptive anal intercourse, a history of gonorrhea, use of illicit drugs, and sexual contact in Los Angeles were identified as independent risk factors for persistent generalized lymphadenopathy. The similarity of these risk factors to those established for AIDS supports the hypothesis of a common etiology for the two diseases. The authors suggest further that the high prevalence rate of persistent generalized lymphadenopathy further supports the hypothesis that AIDS is an uncommon response to a relatively common agent. This was a prospective case-control study of homosexual men. Partici- pants completed a questionnaire covering demographic characteristics, drug use, sexually transmitted disease history, sexual practices, etc., and received a complete physical exam. This battery was repeated at a second visit not less than 3 months later. Laboratory tests were performed after both visits. A total of 519 homosexual men attending six medical practices in central Vancouver completed the study. With the control group, efforts (not entirely successful) were made to match individual cases by age, medical practice where seen, and date of entry into the study. 1) Precursors of AIDS (IIIB), 2) Transmission: Sexual Activity (IIA), 3) Populations: Homosexuals (IA1), 4) Geographic Trends: Canada (IB1) 3B-Sch-6 Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Cooper, David A.; MacLean, Prudence; Finlayson, Robert; Michelmore, Harry M.; Gold, Julian; Donovan, Basil; Barnes, Timothy G.; Brooke, Peter; Penny, Ronald. Acute AIDS Retrovirus Infection: Definition of a Clinical Illness Associated with Seroconversion. The Lancet, 9 March 1985, Vol. 1, No. 8428: 537-540. Centre for Immunology, St. Vincent's Hospital, Sydney; University of New South Wales, New South Wales; Commonwealth Institute of Health, University of Sydney, New South Wales, Australia. In the course of a prospective immunoepidemiological study of homosexual men, 12 subjects were observed to seroconvert within 6 months from a negative reading for AlDS-associated retrovirus antibodies to a positive reading. Of these subjects, 11 had had an acute infectious mononucleosis-like illness, as determined by a review of their clinical files. The illness was of sudden onset and lasted 3 to 14 days. In one subject an incubation period of 6 days after presumed exposure to the AIDS-related virus was determined. For three subjects the collection of multiple serum samples allowed determination of the time of conversion from negative to positive, which was 56, 32, and 19 days after the onset of the acute illness. Associated with conversion were prominent changes in immunological status. There was no change in the absolute numbers of helper T cells before or after conversion, but an increase in the number of suppressor T cells lowered the helper/suppressor T-cell ratio in eight subjects. In three subjects the ratio did not change strikingly; data were not obtained for one subject. These findings support the notion of an acute clinical, immunological, and serological response to infection with AIDS-related virus which should be considered in the diagnosis of mononucleosislike syndromes in groups at high risk for AIDS. From February 1984 to January 1985, homosexual and bisexual men were enrolled in a Sydney, Australia, AIDS project in which data were collected every 6 months for comparative analysis of epidemiology, clinical features, immunology, and serology. The subjects retested at the 6-month follow-up examination who showed a conversion from negative to positive in a test for the presence of AIDS-related virus antibody were included in this study. These patients' clinical files were reviewed for the presence of an acute illness. Changes in their immunological status were also monitored. Twelve homosexual or bisexual men aged 23 to 64 years (mean, 35) in Sydney, Australia, were included in the report. 1) Precursers of AIDS (IIIB), 2) Incubation Period and Disease Stages (IlIC), 3) Geographic Trends: Australia (IB3), 4) Populations: Homosexuals (IA 1) 3B-Coo-7 Author(s): Title: Source: Institution: Findings: Method: Groopman, Jerome E., MD; Mayer, Kenneth H., MD; Sarngadharan, M.G., PhD; Ayotte, David, MPH; Devico, Anthony L., BS; Finberg, Robert, MD; Sliski, Ann H., DSc; Allan, J. Davis, MDj Gallo, Robert C., MD. Seroepidemiology of Human T-Lymphotropic Virus Type III Among Homosexual Men with the Acquired Immunodeficiency Syndrome or Generalized Lymphadenopathy and Among Asymptomatic Controls in Boston. Annals of Internal Medicine, March 1985, Vol. 102, No. 3: 334-337. Divisions of Hematology-Oncology and Infectious Disease, Department of Medicine, New England Deaconess Hospital; Fenway Community Health Clinic; Division of Infectious Disease, Dana-Farber Cancer Center, Boston, Massachusetts; Infectious Disease Division, Department of Medicine, Memorial Hospital, Brown University, Pawtucket, Rhode Island; Department of Cell Biology, Litton Bionetics, Kensington, Maryland; Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland. The authors studied a large cohort of homosexual men with persistent (at least 3 months' duration) generalized (two or more sites outside the groin) lymphadenopathy in a single demographic area (metropolitan Boston) and compared them with AIDS patients and asymptomatic homosexual men for evidence of human T-cell lymphotropic virus type III (HTLV-II) infection. The presence of antibody to HTLV-II among men with AIDS and men with generalized lymphadenopathy suggests that HTLV-II infections are closely related to both disorders. They found that 98% of men with AIDS and more than 90% of men with generalized lymphadenopathy had antibody to HTLV-II, while 21% of the asymptomatic men were positive. Six patients with generalized lymphadenopathy developed AIDS over 2 years; all were seropositive for HTLV-III. Thirty-six asymptomatic men had had sexual contact with a man with AIDS; receptive anal intercourse in this group was associated with positive results for HTLV-II antibody. These data suggest that persistent generalized lymphadenopathy and AIDS are part of a clinical spectrum of HTLV-II infection and that most high-risk homosexual men in some regions of the U.S. have not yet been infected with the virus. In this seroepidemiological study, subjects were classified and compared for the presence of antibody to HTLV-II. All patients provided a comprehensive history and had a physical examination; all were evaluated for infections and neoplastic disorders. Sixty patients with lymphadenopathy had one or more lymph nodes biopsied. Laboratory evaluation was done at least twice for most patients, including immuno- globulin studies, and blood tests for cytomegalovirus and Epstein-Barr virus. Epidemiologic data obtained included sexual practices, known sexual contact with a person who later developed AIDS, and number of lifetime sexual partners. Blood samples were tested for antibody to HTLV-III by enzyme-linked immunosorbent assay. 3B-Gro-8 Sample Size: Policy Keys: Homosexual men were recruited during 1982 and 1983 from a large community-based clinic specializing in sexually transmitted diseases and a large university hospital in Boston, Massachusetts. Seventy-eight patients had persistent unexplained generalized lymphadenopathy for at least 3 months. Forty-five patients had AIDS, and 160 homosexual men without signs or symptoms of either disorder volunteered; the latter were homosexually active (sexual contact with one or more men on at least three occasions over the previous 6 months). 1) Precursors of AIDS (IIIB), 2) Disease Stages (IIIC), 3) Transmission: Sexual Activity (IIA), 4) Cofactors: Demographic Status (ICL), 5) Populations: Homosexuals (IAl), 6) Geographic Trends: U.S. (IB1) Author(s): Title: Source: Institution: Findings: Method: Gold, Jonathan W.M., MD; Weikel, Cynthia S., MD; Godbold, James, PhD; Garcia, Carlos, MD; Urmacher, Carlos, MD; Cunningham-Rundles, Susanna, PhD; Koziner, Benjamin, MD; Pollack, Marilyn, PhD; Gallo, Robert C., MD; Sarngadharan, M.G., PhD; Armstrong, Donald, MD. Unexplained Persistent Lymphadenopathy in Homosexual Men and the Acquired Immune Deficiency Syndrome. Medicine, 1985, Vol. 64, No. 3: 203-213. Infectious Disease (Gold, Weikel, Armstrong), Biostatistics (Godbold), Pathology (Garcia, Urmacher), and Clinical Immunology (Cunningham- Rundles, Koziner, Pollack) Services, Memorial Sloan-Kettering Cancer Center, New York, New York; Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Gallo); Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland (Sarngadharan). This study evaluates the clinical outcome for 93 patients evaluated at a major medical center who presented with diffuse enlargement of the lymph nodes. Between | December 1980 and 31 January 1984, 11 of 93 patients were subsequently diagnosed with AIDS (7 with Kaposi's sarcoma and 4 with opportunistic infections). The diagnosis of AIDS was made after a mean follow-up time of 10.9 months. Compared with patients with lymphadenopathy who have not developed AIDS, those in whom AIDS has been recognized had significantly lower mean lymphocyte proliferative responses to Escherichia coli, lower hemoglobin concentrations, platelet counts, and lymphocyte counts, and higher immunoglobulin A levels. None of these abnormalities, however, was unique to patients who developed AIDS. There were no significant differences in the prevalence of antibodies, including antibodies to Epstein-Barr virus and cytomegalovirus. Among patients for whom lymph node biopsies were performed, none had distinctive findings to distinguish them from patients who did not develop AIDS. Lymphadenopathy regressed in six patients after a mean of 14.8 months. However, in one of these patients lymphadenopathy recurred after 4 months. Case reports of each of the 11 AIDS cases are included. This study described findings in patients with persistent lymphadenopathy and their results on follow-up. Routine laboratory tests and serological tests were performed with standard methods. Specimens of urine, semen, saliva, and buffy coat were cultured for viruses, and stool cultures were done in some cases. Human T-cell lymphotropic virus type [Il antibody was measured by enzyme-linked immunosorbent assay. Samples giving negative and equivocal results were also tested by the Western blot technique. The earliest available specimen from each patient was tested, and serial specimens were tested for 44 subjects. Immunologic tests were done when possible (lymphocyte cell surface marker studies with monoclonal antibodies of the OKT series; human 3B-Gol-9 Sample Size: Policy Keys: leukocyte antigen A, B, C, and DR typing; lymphocyte proliferative responses; and natural killer cell activity). Questionnaires pertaining to medical history of lymphadenopathy, history of sexually transmitted diseases, sexual practices, and drug use were filled out by each of the patients. Patients were followed for a mean of 20.8 months. The 93 patients in this study were all homosexual men with lymphadenopathy. Ages ranged from 21 to 54 years (mean, 34.3) at the time first seen. Of these, 64 were white, 12 Hispanic, 16 black, and one Oriental. Patients were followed for a mean of 20.8 months. The mean duration of lymphadenopathy before the first clinic visit was 10.5 months, while for 43 of the patients the first observation of lymphadenopathy was made by the investigators. The mean number of estimated lifetime sexual partners was 1,422 (median, 377; range, 15 to 7000). All but two patients had a history of at least one sexually transmitted disease. Only three said they had injected drugs either intravenously or subcutaneously. 1) Precursors of AIDS (IIIB), 2) Disease Stages (IIIC), 3) Populations: Homosexuals (IA 1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Laurence, Jeffrey, MD; Brun-Vezinet, Francoise, MD; Schutzer, Steven E., MD; Rouzioux, Christine, PhD; Klatzmann, David, MD; Barre- Sinoussi, Francoise, PhD; Chermann, Jean-Claude, PhD; Montagnier, Luc, MD. Lymphadenopathy-Associated Viral Antibody in AIDS: Immune Correlations and Definition of a Carrier State. The New England Journal of Medicine, 15 November 1984, Vol. 311, No. 20: 1269-1273. Division of Hematology-Oncology, Department of Medicine, New York Hospital-Cornell Medical Center, New York; Department of Immunology, Rockefeller University, New York; Laboratoire de Virologie, Hopital Claude Bernard, Paris; Laboratoire d'Immunologie Nephrologique et de Transplanation, UER Pitie-Salpetriere, Paris; and Institut Pasteur, Departemente de Virologie, Paris, France. These researchers investigated whether serologic evidence of lymphadenopathy-associated virus (LAV), a human T-cell virus, was associated with the acquisition and transmission of AIDS. Serum from 17 of 25 patients with AIDS contained antibody to LAV. These 17 patients represented all 5 of the adults with cancer as well as 6 of 12 adults and six of eight children with opportunistic infections, with or without Kaposi's sarcoma. All of eight homosexual men with generalized lymphadenopathy or AIDS-related complex and five homosexual men with AIDS precursors who later developed AIDS also had this antibody. These researchers did not find LAV antibodies in 99 of 100 healthy blood donors or in 23 patients who were born with deficiencies of the immune system. An AIDS carrier state seems to be indicated by the transfer of LAV from asymptomatic mothers whose immune system functions were normal to their children. These authors state that these data offer a basis for the hypotheses that (1) LAV is a marker for AIDS, (2) LAV may be carried and transmitted in the absence of clinical findings or laboratory T-cell abnormalities, and (3) LAV is probably an important causative agent in AIDS and its precursors. Antibody to LAV in blood serum samples from participants was deter- mined by an enzyme-linked immunosorbent assay (ELISA). Correlation with a radioimmunoprecipitation assay confirmed the validity of the ELISA results. T-lymphocyte subpopulations were determined by indirect immunofluorescence. Serum samples were obtained from 25 patients with clinically docu- mented AIDS: 17 adults with either cancer (Kaposi's sarcoma or B-cell lymphoma) or opportunistic infection with or without Kaposi's sarcoma, and eight children 8 to 24 months old. Five patients with an AIDS precursor defined after the fact were also studied. In these patients AIDS developed within 2 to 11 months after the initial serum sample was collected. Other subjects were eight homosexual men with generalized lymphadenopathy, six of whom fulfilled the criteria for diagnosis of AIDS-related complex, nine healthy persons with risk factors for AIDS, and 23 patients with congenital immunodeficiencies. One hundred 3B-Lau-10 randomly selected blood donors from two Paris hospitals were also included in the study. Policy Keys: 1) Precursors of AIDS (IIIB), 2) Seroprevalence: Marker for AIDS (VB2) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Klein, Robert S., MD; Harris, Carol A., MD; Butkus-Small, Catherine, MD; Moll, Bernice, PhD; Lesser, Martin, PhD; Friedland, Gerald H., MD. Oral Candidiasis in High-Risk Patients as the Initial Manifestation of the Acquired Immunodeficiency Syndrome. The New England Journal of Medicine, 9 August 1984, Vol. 311, No. 6: 354-358. Division of Infectious Diseases, Department of Medicine, Montefiore Medical Center and North Central Bronx Hospital, Bronx; Division of Immunopathology, Department of Pathology, and Department of Biostatistics, Montefiore Medical Center, Bronx; Departments of Medicine, Pathology, and Community Health, Albert Einstein College of Medicine, Bronx, New York. This study evaluated the frequency with which a diagnosis of infection of the mouth or throat with Candida preceded the diagnosis of AIDS in patients at risk. Twenty-two patients with significant risk factors for AIDS (generalized lymph node enlargement and abnormalities of white blood cells) and oral Candida infections were compared with 20 patients who had the same risk factors for AIDS but no oral Candida infection and 20 patients with documented AIDS. Thirteen of 22 patients with oral Candida infections (59%) subsequently developed AIDS (defined as development of a severe opportunistic infection or Kaposi's sarcoma) at a median of 3 months of follow-up. None of the patients with the AIDS risk factors who did not have oral Candida infections developed clinically evident AIDS when followed up for a median of 12 months. In the patients with oral Candida infections who went on to develop AIDS, abnormalities in white blood cells were particularly pronounced (helper/suppressor T-cell ratio of <0.51, compared with >0.60 in a group in which none of four developed AIDS). The authors conclude that in patients at high risk for AIDS, the presence of oral Candida infections predicts the development of serious opportunistic infections more than 50% of the time. Whether the remainder will develop AIDS is not yet known. This was a prospective case-control study of patients from the Montefiore and North Central Bronx Hospitals in New York City from September 1981 through July 1983. Complete physical exams were conducted, with oral candidiasis diagnosed when, in the presence of characteristic lesions of the mouth, examination of scrapings by a potas- sium hydroxide preparation or Gram stain revealed fungi. Extensive histories were taken, with an emphasis on sexual practices, drug use or abuse, travel, and exposure to blood products. The primary study group was composed of 22 patients who were either intravenous (I.V.) drug abusers or homosexual or bisexual males; there were 18 males and 4 females, with a mean age of 30 years. Eleven (50%) of the group were Hispanic, 9 (41%) were black, and 2 (9%) were white; 3B-Kle-11 Policy Keys: 16 (73%) were [.V. drug abusers. A second (control) group consisted of 20 persons with documented AIDS; there were 16 males and 4 females, with a mean age of 36.5 years. Thirteen (65%) were Hispanic, 6 (30%) were black, and 1 (5%) was white. A third (control) group consisted of 20 persons with AIDS-related complex (ARC) without candidiasis; there were 18 males and 2 females, with a mean age of 31.4 years. Twelve (60%) were Hispanic, and 8 (40%) were black. 1) Precursors of AIDS (IIIB), 2) Incubation Period and Disease Stages (111C) Author(s): Title: Source: Institution: Findings: Method: Sample: Abrams, Donald [., MD; Lewis, Brian J., MD; Beckstead, Jay H., MD; Casavant, Conrad A., MD; Drew, W. Lawrence, MD, PhD. Persistent Diffuse Lymphadenopathy in Homosexual Men: Endpoint or Prodrome? Annals of Internal Medicine, June 1984, Vol. 100, No. 6: 801-808. Departments of Medicine, Pathology, and Laboratory Medicine, University of California at San Francisco; Departments of Medicine, Pathology, and Laboratory Medicine, Mt. Zion Hospital and Medical Center, San Francisco, California. Seventy homosexual men with unexplained chronic generalized lymphadenopathy were prospectively studied to examine the natural history of the condition in this population. These men had demographic, clinical, and laboratory findings similar to those of homosexual patients with AIDS. Pathologic examination of lymph node biopsies from 35 patients showed growth of the lymph follicles, and most patients had recurrent, non-life- threatening infections. All had evidence of immune system dysfunction and lowered helper/suppressor T-cell ratios. To date of publication (June 1984), none of the patients had developed AIDS. Based on these first- year findings, the authors suggest that the lymphadenopathy syndrome may be an alternative response to the AIDS agent. This prospective study examined homosexual men with lymphadenopathy (of more than 6 months' duration) but without AIDS. Clinical histories and physical exams were done by two physicians, including drawing blood samples for testing. Blood testing included a complete blood count, serum chemistry panel, determination of helper/suppressor T-cell ratio, quantitative immunoglobulins, hepatitis B virus antigens and antibodies, cytomegalovirus antibodies, Epstein-Barr virus antibodies, anti-Toxoplasa immunoglobulin G, and other tests. Semen samples were cultured for virus, and three stool specimens were examined for parasites and eggs. Twenty patients responded to a self-administered Centers for Disease Control questionnaire on detailed demographic data, history of sexually transmitted diseases, drug use, and sexual practices. This study reports first-year findings. Seventy San Francisco homosexual men with lymphadenopathy who were being treated at the Lymphoma Clinic were studied in the 12 months from November 1981 to November 1982. Patients with a history of lymph system malignancy, Kaposi's sarcoma, or Pneumocystis carinii pneumonia were excluded, as were those with current illness known to be associated with generalized lymphadenopathy and those taking prescription medications that might cause enlargement of lymph nodes. All patients eligible for inclusion agreed to participate. Sixty men were white, six were Hispanic, and four were black; their ages ranged from 19 to 43 years (mean, 32.6). Patients had a mean of 91 different sexual partners during the year prior to developing symptoms of lymphadenopathy. 38~-Abr-12 Policy Keys: 1) Precursors of AIDS: Lymphadenopathy (IIIB), 2) Disease Stages (IIIC), 3) Populations: Homosexuals (IA 1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lozada-Nur, F., DDS, MS; Silverman, S. Jr., MA, DDS; Migliorati, C., DDS, MS; Conant, M., MD; Abrams, D., MD; Volberding, P.A., MD; Greenspan, D., BDS. The Diagnosis of AIDS and AIDS Related Complex in the Dental Office: Findings in 171 Homosexual Males. California Dental Association Journal, June 1984: 21-25. Departments of Oral Medicine, Dermatology, and Medicine, Schools of Dentisty and Medicine, University of California, San Francisco, California. The most frequent tumor among San Francisco AIDS patients seen at an oral-medicine clinic was Kaposi's sarcoma (KS), which involved the mouth in 55% of patients. In six patients, the mouth was the only KS site and was the chief basis for the diagnosis of AIDS. When oral KS occurred, the palate was involved 77% of the time, and a third of the oral KS patients had multiple oral sites. Seven patients had oral squamous carcinomas (tumors of the outer layer of skin that grow and spread rapidly), which in at least one patient preceded the diagnosis of AIDS by 6 years. Six of the seven oral carcinomas occurred in the tongue. Of the three lymphoma patients, one had an oral manifestation as the first AIDS finding. The high occurrence of oral cancer indicates that this tumor is an important AIDS-related condition. Case reports of oral KS and other tumor involvement in AIDS patients were reviewed. A total of 171 AIDS and AIDS-related complex patients from San Francisco, all homosexual males, were referred to the Oral Medicine Clinic at the University of California in San Francisco and studied between August 1981 and March 1984. 1) Precursors of AIDS: Oral KS (IIIB), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA), 3) Populations: Homosexuals (IA1) 3B-Loz-13 Author(s): Title: Source: [nstitution: Findings: Method: Mathur-Wagh, Usha; Spigland, Ilya; Sacks, Henry S.; Yancovitz, Stanley R.; William, Daniel C.; Enlow, Roger W.; Winchester, Robert J.; Rorat, Edwarda; Klein, Michael J.; Mildvan, Donna. Longitudinal Study of Persistent Generalised Lymphadenopathy in Homosexual Men: Relation to Acquired Immunodeficiency Syndrome. The Lancet, 12 May 1984, Vol. 1, No. 8385: 1033-1038. Departments of Medicine and Pathology, Beth Israel Medical Center, Hospital for Joint Diseases Orthopedic Institute, New York; Department of Medicine, Mount Sinai Hospital, Mount Sinai School of Medicine of the City University of New York; Department of Medicine, New York University Medical Center; Division of Virology, Montefiore Hospital and Medical Center, Albert Einstein College of Medicine, Bronx, New York. Clinical, immunological, and microbiological features were studied prospectively to determine whether lymphadenopathy in apparently healthy homosexual men was the expression of a wider spectrum of AIDS. After 15 to 30 (median, 22) months of follow-up, 8 of 42 homosexual or bisexual men with persistent (at least 3 months) generalized lymphadenopathy progressed to AIDS. The median duration of lymphadenopathy before the diagnosis of AIDS was 21 months (range, 4 to 42). The other patients either remained unchanged or improved clinically during that time. Patients in whom AIDS ultimately developed were distinguished by the presence of more severe immunological abnormalities from the beginning of the study, including a lower absolute number of helper T cells and a higher frequency of decreased reactivity to mumps antigen and herpes simplex virus. A reduction in lymph node size was seen in 29% of the patients who did not progress to AIDS. Whether this is a sign of recovery remains to be seen. Some clinical abnormalities described for AIDS were observed in most of the patients with persistent, generalized lymphadenopathy. The cellular immuno- deficiency that characterizes AIDS, that is, the decreased levels of helper T cells, was present in 95% of the patients tested. The authors conclude that the clinical spectrum of diseases associated with AIDS is considerably wider than that adopted by the Centers for Disease Control for purposes of surveillance, and that continued longitudinal observations will be needed to determine the extent of the relations between these clinical entities and AIDS. For this longitudinal study, homosexual and bisexual men with unexplained lymphadenopathy were referred to Beth Israel Medical Center by physicians and clinics in New York City. Consenting individuals were included in a 15- to 30-month longitudinal study. All patients gave a detailed medical and social history in response to a questionnaire and had a complete physical examination. Microbiological studies on specimens of urine, semen, and blood and tissue cultures of lymph node, throat, and rectum samples were performed; material from lymph node biopsies was cultured for bacteria, fungi, mycobacteria, and, in some cases, viruses. Delayed skin hypersensitivity to tubercuiin, Candida, and mumps virus antigens was tested. T-cell subpopulations 3B-Mat-14 Sample Size: Policy Keys: were quantitated by immunodiffusion with OKT3, OKT#4, and OKT& monoclonal antibodies. Forty-two homosexual and bisexual males in New York City participated; the subjects were patients with unexplained persistent generalized lymphadenopathy who were referred between February 1981 and May 1932, 1) Precursors of AIDS: Lymphadenopathy (IIIB), 2) Incubation Period and Disease Stages (IIIC), 3) Immunological Aspects (IIE), 4) Cofactors: Immunological Abnormalities (IC3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Kalish, S.B.; Ostrow, D.G.; Goldsmith, J.; Hsu, C.C.S.; Chmiel, J.S.; Wallemark, C.-B.; Phair, J.P. The Spectrum of Immunologic Abnormalities and Clinical Findings in Homosexually Active Men. The Journal of Infectious Diseases, February 1984, Vol. 149, No. 2, 148- 156. Departments of Medicine, Psychiatry, Community Health and Preventive Medicine, and the Cancer Center, Northwestern University Medical School; Veterans Administration Lakeside Medical Center; Howard Brown Memorial Clinic, Chicago, Illinois. Clinical and laboratory evaluations of 181 men were performed; the population studied included 131 homosexual or bisexual men (who were divided into three groups by symptoms and abnormal physical examina- tion findings), 39 heterosexual men who served as controls, and 11 men with AIDS. The presence of specific symptoms and/or lymphadenopathy in homosexual men was associated with disordered functioning of the immune system. A large percentage of asymptomatic, homosexually active men had abnormalities in lymphocyte numbers, subpopulations, and subclasses. Symptomatic individuals had clinical findings, immunological alterations, and abnormal blood cell formation similar to those found in patients with AIDS. These data suggest that clinical evaluation in conjunction with laboratory studies identify individuals at increased risk of developing AIDS. Blood specimens were obtained from all individuals in the morning; lymphocytes were separated, and specific laboratory methods were used to identify T lymphocytes and T-cell subsets as well as B lymphocytes. Simultaneous blood cell counts and other routine blood tests were also performed, as were serum immunoglobulin determinations. Tests were performed for delayed skin hypersensitivity to Candida, trichophytin (a ringworm fungus), a tuberculosis agent protein, histoplasmin (a fungal product), and mumps virus protein. Results were observed within 48 hours of the injection and compared with a scale indicating the presence of the pathogen or disease. The results of the tests were evaluated with- out knowledge of the medical condition, sexual preference, or group classification of the individual involved. A total of 181 men were included in this report. All participants except the 39 heterosexual controls gave a medical history and underwent a physical examination and was then classified into one of four groups according to the results. Group | consisted of Il individuals fulfilling the Centers for Disease Control criteria for AIDS. The 131 homosexual or bisexual men made up groups 2 through 4. These individuals were recruited from a group of participants in a previous trial of hepatitis B vaccine or referred by private physicians or sexually transmitted disease clinics. Group 2 consisted of 39 homosexually active or bisexual men with two or more of the following symptoms: unexplained lymphadeno- pathy involving two or more lymph nodes for more than 2 months, fever of unknown cause for more than 3 weeks, unexplained diarrhea or 3B-Kal-15 Policy Keys: anorexia for more than 2 months resulting in loss of 10% of their body weight, unexplained fatigue for more than 3 months, extensive herpes, fungal infection of the mouth, or unexplained skin rashes. Group 3 con- sisted of three homosexually active or bisexual men who met one of the criteria for group 2. Group 4 consisted of 60 homosexually active or bisexual men who had none of the symptoms or findings at least 3 months before the evaluation and 6 months after the evaluation; this group served as homosexually active controls. Group 5, the 39 heterosexual controls, were asymptomatic heterosexual men with no known underlying disorder. 1) Precursors of AIDS (IIB), 2) Immunological Aspects (IIE), 3) Populations: Homosexuals (IA 1) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Manger, B.J.; Burmester, G.R.; Grammatzki, M.; Nusslein, H.; Bienzle, U.; Kalden, J.R. Immunological Studies in Homosexual Men with Unexplained Lymphadenopathy. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. I: 73-74. Institute for Clinical Immunology and Rheumatology, Medical School Erlangen, Erlangen, Federal Republic of Germany (Manger, Burmester, Grammatzki, Nublein, Kalden); Landesinstitut fur Tropenmedizin, Berlin, Federal Republic of Germany (Bienzle). This study was performed to examine the immune function of 92 homosexual men from West Berlin who had unexplained lymph node swelling in two or more areas. The helper/suppressor T-cell mean ratio was 1.9 in a healthy heterosexual population. In homosexual men with lymphadenopathy, a significant decrease in this ratio was recorded, mainly due to a decrease in the absolute number of helper T-cells. These data indicate disturbed immune function in homosexual men with lymphadenopathy associated with symptoms such as fever, diarrhea, weight loss, and night sweats. These men will be followed up to determine whether a pre-AIDS syndrome can be identified. This study compared immunological function in male homosexuals with lymphadenopathy, apparently healthy homosexual males, and healthy controls. Mononuclear cells isolated from peripheral blood samples were detected by indirect immunofluorescence. A total of 92 male homosexuals with lymphadenopathy from the Federal Republic of Germany were studied, along with 14 male homosexuals who were apparently healthy and 50 healthy homosexual controls. 1) Precursors of AIDS (IIIB), 2) Populations: Homosexuals (IAl), 3) Geographic Trends: Europe (West Germany) (IB4) 3B-Man-16 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Cavaille-Coll, M.; Messiah, A.; Klatzmann, D.; Rozenbaum, W.; Lachiver, Dominique; Kernbaum, S.; Brisson, Edith; Chapuis, Francoise; Blanc, Catherine; Debre, P.; Gluckman, J.-C. Critical Analysis. of T Cell Subset and Function Evaluation in Patients with Persistent Generalized Lymphadenopathy in Groups at Risk for AIDS. Clinical and Experimental Immunology, 1984, Vol. 57, No. 3: 511-519. Laboratoire d'Immunologie Nephrologique et de Transplantation, UER Pitie-Salpetriere (Cavaille-Coll, Klatzmann, Brisson, Chapuis, Gluckman); Departement de Sante Publique (Messiah, Rozenbaum); Laboratoire d'Immunologie Cellulaire et Tissulaire, Groupe Hospitalier Pitie-Salpetriere (Blanc, Debre, Klatzmann); Institut Arthur Vernes (Lachiver); Clinique des Maladies Infectieuses et Tropicales, Hopital Claude Bernard (Kernbaum), Paris, France. To determine whether there is a distinct immunological profile that discriminates between healthy homosexual men and those expressing persistent generalized lymphadenopathy (PGL), and which of the abnormalities in PGL are most indicative of patients who will eventually develop AIDS, this study evaluated T-cell subsets and test tube cell growth responses. The profiles of 44 symptom-free homosexual men, 42 patients with PGL, and 30 cases of AIDS were compared with those of blood bank volunteer controls and with each other. Symptom-free homosexuals, PGL patients, and AIDS patients demonstrated various degrees of the same type of abnormal characteristics. None of the T- cell subset variables could correctly classify more than 71% within the healthy homosexual group and the two patient groups. These authors conclude that there is a continuity between PGL and AIDS patients in the range of observed immunological abnormalities, without clear-cut boundaries that can distinguish these patient populations. They conclude that it will not be possible to devise T-cell subset parameters to serve as diagnostic and prognostic evidence of PGL or AIDS. This case-control study examined peripheral blood mononuclear cells, separated from a sample of anticoagulant-treated fresh blood and centrifuged over Ficoll-Hypaque. T-cell subsets were quantified by indirect immunofluorescence staining or by using a cell analyzer. A group of 44 symptom-free French homosexual men, as well as 42 patients with PGL and 30 cases of AIDS referred between January 1982 and October 1983, were compared with 50 blood bank volunteer (male and female) controls. 1) Precursors of AIDS: Immunological Predictors (IIIB), 2) Immunological Aspects (IIE), 3) Populations: Homosexuals (IAl), 4) Geographic Trends: Europe (France) (IB4) 3B-Cav-17 Author(s): Title: Source: Institution: Findings: Method: Gilmore, Norbert J., PhD, MD; Prchal, Jaroslav F., MD; Jothy, Serge, MD, PhD. Persistent Generalized Lymphadenopathy in Homosexual Men: Clinical, Pathological and Immunologic Characteristics. Canadian Medical Association Journal, | November 1983, Vol. 129: 960- 965. Divisions of Clinical Immunology (Gilmore) and Hematology (Prchal), Department of Medicine, and Department of Pathology (Jothy), Royal Victoria Hospital and McGill University, Montreal, Canada. This article reports baseline results of a prospective study of the clinical, pathological, and immunological features of persistent lymphadenopathy in homosexual men. A group of homosexual Caucasian males with lymphadenopathy in at least two noncontiguous sites outside the groin for more than 5 months were studied. These men were compared with a group of apparently healthy homosexual males and another group of apparently healthy heterosexuals. The mean duration of the lymphadenopathy was 10.6 months. Enlarged nodes were found in more than four anatomic areas in 16 patients; 2 had lymphadenopathy restricted to two noncontiguous areas. Many subjects claimed that the size of their nodes fluctuated for no identifiable reason; on palpation, the nodes were "fleshy" and nontender. All 18 subjects had extreme malaise; 90% had additional symptoms (fever, night sweats, weight loss, or gastrointestinal dysfunction). Most of the lymph nodes biopsied showed striking hyperplasia (increased numbers of cells), distortion and confluence of follicles, vascular hyperplasia, capillary arborization (branching), and endothelial cell enlargement. Skin testing for recall anergy showed diminished responses in the lymphadenopathy patients. In addition, the number and proportion of circulating helper T cells was decreased and the mean number of suppressor T cells was increased in these patients. No biopsies revealed evidence of granuloma (nodular lesions resulting from inflammatory reactions), lymphoma, or Kaposi's sarcoma. Persis- tent generalized lymphadenopathy in previously healthy homosexual men appears to be a distinct syndrome of unknown etiology; it may also be related to the AIDS syndrome. All laboratory testing was done with coded material. Anergy testing was performed by staff who did not know the sexual orientation of the control groups. Lymphadenopathy was graded by the number of noncontiguous sites in which nodes greater than 0.5 cm in diameter were present; extent of the adenopathy was expressed as the sum of the number of areas involved. Splenomegaly (enlargement of the spleen) was confirmed by clinical examination, and lymphadenopathy between the lungs was assessed by chest X-rays. The numbers of leukocytes and lymphocytes in peripheral blood were determined and T-cell subpopu- lations were counted by direct immunofluorescence microscopy with OKT3, OKT4, and OKT8 monoclonal antibodies. The levels of immuno- 3B-Gi1-18 Sample Size: Policy Keys: globulins G, A, and M and serum complements C3 and C4 in serum were quantified with a nephelometer (an instrument that estimates particle density). A total of 38 Caucasian male volunteers were studied; all had been living in North America for the last 10 years, had been sexually active, and claimed exclusive sexual behavior. A group of 18 homosexual men (age range, 23 to 41 years) who had had unexplained generalized lymphadeno- pathy with no evidence of other illnesses or infections were compared with 10 apparently healthy homosexual men (age range, 24 to 42 years) and 10 apparently healthy heterosexual men (age range, 26 to 42 years). 1) Precursors of AIDS: Lymphadenopathy (IIIB), 2) Populations: Homosexuals (IA 1), 3) Immunological Aspects (IIE) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Eyster, Elaine M., M.D.; Goedert, James J., M.D.; Poon, Man-Chiu, M.D.; Preble, Olivia T., Ph.D. Acid-labile Alpha Interferon: A Possible Preclinical Marker for the Acquired Immunodeficiency Syndrome in Hemophilia. The New England Journal of Medicine, 8 September 1983, Vol. 309, No. 10: 583-586. Division of Hematology, Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania; Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland; Division of Hematology/Oncology, Department of Medicine, University of Alabama in Birmingham, and Birmingham Veterans Administration Medical Center, Birmingham, Alabama; Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, Maryland. Stored plasma and serum from three hemophiliac patients with AIDS were studied for the level of alpha interferon and evaluated against levels found in 46 patients with asymptomatic hemophilia. Persistently elevated levels of the acid-labile (destroyed by acid) form of alpha interferon were found in all three patients. In two patients, the appear- ance of circulating alpha interferon preceded the onset of clinical disease by 3 to 10 months. In contrast, alpha interferon levels were not elevated in 43 of 46 unselected patients with hemophilia; 3 of these patients had transient elevations. The authors suggest that acid-labile alpha interferon may be a marker that can be used to identify AIDS-affected asymptomatic members of high-risk groups before the onset of clinical disease. This study compares hemophiliacs with AIDS and hemophiliacs without AIDS, measuring levels of acid-labile alpha interferon. Interferon was quantitated with the use of human GM250¢4 fibroblasts (connective-tissue cells). The stability of alpha interferon at an acidity level of pH 2 was determined. Each sample was tested in duplicate. Three hemophiliacs with AIDS were compared with 46 hemophiliacs without AIDS. The three subjects included a 10-year-old white boy from Pennsylvania with severe hemophilia A treated at home with factor VIII concentrate who had Pneumocystis carinii pneumonia and AIDS, a 36- year-old white man from Pennsylvania who had mild hemophilia A, treated with monthly infusions of fresh-frozen plasma and occasionally with factor VIII concentrate, and had multiple opportunistic infections and AIDS, and a 55-year-old white man from Alabama with severe hemophilia A, treated at home with factor VIII concentrate, who had P. carinii pneumonia, Mycobacterium avium-intracellulare, and AIDS. The control group consisted of 37 unselected male patients with hemophilia A and 9 with hemophilia B. They included 45 whites and | black and ranged in age from 6 to 61 years (median, 24.5). Only one was homosexual. All were seen for routine clinical visits at a Pennsylvania medical center between September and December 1982. 3B-Eys-19 Policy Keys: 1) Precursors of AIDS (IIIB), 2) Populations: Hemophiliacs (IA3) [II. Characteristics of Disease C. Incubation Period and Disease Stages Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Taylor, Jeremy M.G.; Schwartz, Kendra; Detels, Roger. The Time from Infection with Human Immunodeficiency Virus (HIV) to the Onset of AIDS. The Journal of Infectious Diseases, October 1986, Vol. 154, No. 4: 694- 697. Divisions of Biostatistics and Epidemiology, School of Public Health, University of California, Los Angeles, California. This study examined the distribution of times from infection with human immunodeficiency virus (HIV) to development of AIDS and the distri- bution of times from infection to appearance of a major immunologic abnormality. The authors estimate that the probability of developing AIDS within 2 years of infection is 2% and within 4 years roughly 11%. The study also shows that approximately 18% and 30% of infected individuals will develop appreciable immunodeficiency within 3 and 4 years after infection with HIV, respectively, Using a mathematical modeling approach, the authors estimate that, by July 1987, the total number of cases of AIDS will be 51,000 and that more than half of the cases that will develop between July 1986 and July 1987 will be in individuals who were infected before 1984. Tests for HIV antibody and immunologic status were performed for all subjects, who were followed up for 4 years. Three relevant dates were established for each person: (1) the earliest possible date of infection; (2) the last possible date of infection; and (3) the date of diagnosis of AIDS, the date of loss to follow-up, or March 1986 if the individual was still being followed up. Statistical methods were used to estimate the distribution of times from infection to diagnosis of AIDS. Subjects enrolled include 177 young homosexual men recruited from the University of California-Los Angeles Gay and Lesbian Association and from a health club in Los Angeles. Half the participants enrolled in the spring of 1982 and half in the summer of 1983. Sixty-two men were seropositive at their first visit, and 16 seroconverted during the course of the study. Thirty-eight men were lost to follow-up, 23 of whom were seronegative at their last visit. Twenty-three men developed appreciable immunodeficiency, including nine cases of AIDS. Data for the 99 men who were persistently seronegative were not included in the analysis. 1) Incubation Period and Disease Stages (I1IC) 3C-Tay-1 Author(s): Titles Source: Institution: Findings: Method: Sample Size: Mann, Jonathan M.; Colebunders, Robert L.; Khonde, Ndangi; Nzilambi, Nzila; Jansegers, Leopold; McCormick, Joseph B.; Quinn, Thomas C.; Bila, Kapita; Kalemba, Kapela; Bosenge, Ngaly; Malonga, Miatudila; Francis, Henry; Piot, Peter; Curran, James W. Natural History of Human Immunodeficiency Virus Infection in Zaire. The Lancet, 27 September 1986, Vol. 2, No. 8509: 707-709. Projet SIDA, Department of Public Health, Kinshasa, Zaire (Mann, Colebunders, Nzilambi, Bosenge, Francis); AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Mann, Curran); Mama Yemo Hospital, Kinshasa, Zaire (Khonde, Jansegers, Bila, Kalemba); Belgian-Zairian Medical Cooperation (Colebunders); Institute of Tropical Medicine, Antwerp, Belgium (Colebunders, Piot); Department of Public Health, Republic of Zaire, Kinshasa (Malonga); Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (Quinn, Francis); Special Pathogens Branch, Viral Diseases Division, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (McCormick). To estimate the rate of progression of human immunodeficiency virus (HIV) infection in Zaire, 67 asymptomatic seropositive subjects and 113 seronegative controls were studied over 16 months. AIDS had developed in one seropositive and no seronegatives; ARC or generalized lymphadenopathy had developed in eight seropositives and one seronegative; and minimal lymphadenopathy had developed in 19 seropositives and eight seronegatives. Of the 58 seropositives who did not participate in the follow-up, information was available for 44. One had developed AIDS, and four possibly had ARC. HIV-related outcomes may have been more frequent among nonparticipating seropositives than among those who did participate. The rates of progression observed in this study are similar to those reported for U.S. and European homosexual and bisexual men. Subjects were first given a physical examination to look for signs of AIDS-related conditions; only healthy individuals were included in the study. Serum samples were tested for HIV antibody. Seropositives and seronegatives were matched by age and sex. Each person was requested to participate in a follow-up interview and examination. Of the participants responding, those who had developed AIDS, ARC, generalized lymphadenopathy, or minimal lymphadenopathy were identified. In October 1984, 2,400 of 2,492 (96%) employees at Mama Yemo Hospital in Kinshasa, Zaire, were enrolled in a survey of HIV infection. Of these, 125 healthy seropositive personnel without signs or symptoms of AIDS and 145 age- and sex-matched seronegative controls were identified. Follow-up examinations were conducted on 67 seropositives (38 men, 29 women) and 113 seronegatives. 3C-Man-2 Policy Keys: 1) Disease Stages: Rates of Progression (IIIC), 2) Geographic Trends: Africa (Zaire) (IB5) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Weber, J.N.; Rogers, L.A4 Scott, Ks Berrie, Eg Harris, J.R.W. Wadsworth, J.; Moshtael, O.; McManus, T.; Jeffries, D.J.; Pinching, A.J. Three-Year Prospective Study of HTLV-III/LAV Infection in Homosexual Men. The Lancet, 24 May 1986, Vol. 1, No. 8491: 1179-1182. Departments of Immunology, Virology, and Epidemiology and Praed Street Clinic, St. Mary's Hospital and Medical School, London, England. A cohort of homosexual men was studied prospectively to assess the progression of human T-cell lymphotropic virus type [lI/lymphadenopathy-associated virus (HTLV-III/LAV) infection and AIDS. Of the 33 symptom-free London homosexual men who had evidence of HTLV-III/LAV infection at entry in the study, 4 (12%) pro- gressed to AIDS, 16 (48%) progressed to persistent lymphadenopathy, and 13 (40%) remained symptom free. A further 15 men tested positive during the course of the study (7% per year), of whom & progressed to persistent lymphadenopathy. T-cell ratios at entry in the study were not helpful in predicting which subjects would develop infection or symptoms. The strongest association with prognosis was an episode of sexually transmitted disease in the 6 months before entry. The authors conclude that intercurrent infection may be an important cofactor in the acquisition of HTLV-III/LAV infection, and in subsequent disease progression. In this 3-year prospective study, subjects were seen one, two, or three times at approximately l-year intervals. At each visit the men answered a detailed questionnaire on sexual and drug history, travel, recent sexually transmitted diseases, and medical history. Each subject was also given a full physical examination. A cohort of 170 symptom-free London homosexual men was established at the beginning of the study (1982-83). A year later (1983-84), 133 men were reevaluated, and 103 were seen for a third time in 1984-85. None at entry had a risk factor for AIDS other than homosexuality; in particular, none was an intravenous drug abuser, hemophiliac, or recipient of blood transfusion or other blood products. More than half of the volunteers answered an advertisement in a homosexual newspaper, and the balance were previous attendees at a clinic for sexually transmitted diseases. 1) Disease Stages (IlIIC), 2) Cofactors: Recent STD (IC3), 3) Populations: Homosexuals (IAl), 4) Geographic Trends: Europe (U.K.) (IB4) 3C-Web-3 Author(s): Title: Source: Institution: Findings: Coates, Randall A., MD, MHSc, FRCPC; Soskolne, Colin L., PhD; Read, Stanley E., MD, PhD, FRCPC; Fanning, Mary M., MD, PhD, FRCPC; Klein, Michel M., MD, MSc; Shepherd, Frances A., MD, FRCPC; Calzavara, Liviana, PhD; Johnson, J. Kenneth, MD; O'Shaughnessey, Michael V., PhD. A Prospective Study of Male Sexual Contacts of Men with AIDS-Related Conditions (ARC) or AIDS: HTLV-II Antibody, Clinical, and Immune Function Status at Induction. Canadian Journal of Public Health, May-June 1986, Vol. 77: 26-32. Departments of Preventive Medicine and Biostatistics (Coates, Soskolne, Calzavara, Johnson), Medicine (Coates, Read, Fanning, Shepherd), Pediatrics (Read), Microbiology (Read), and Pathology (Klein), University of Toronto, Ontario; Department of Health Services Administration and Community Medicine, University of Alberta, Alberta (Soskolne); Laboratory Centre for Disease Control, Health and Welfare, Ottawa, Ontario, Canada (O'Shaughnessey). Homosexual contacts of AIDS and AIDS-related condition (ARC) patients were studied prospectively to assess infectivity and progression of the disease. The mean time from last sexual contact with an AIDS or ARC patient (the primary case) to recruitment in the study was 8.8 months. A mean of 4.7 months of follow-up have been completed for the 248 cohort members. At presentation, 59% of the cohort were positive for human T-cell lymphotropic virus type III (HTLV-II) antibody, while the remainder were seronegative. Nearly 45% of the seronegative subjects last had sexual contact with their primary cases more than 6 months prior to recruitment. Since most authorities consider that individuals will seroconvert within 6 months of infection, the authors suggest that infection is not necessarily established despite sexual contact with an infectious individual. The authors did not, however, look at specific sexual practices to determine which may be safer or riskier than others. During the follow-up period, the rate of development of lymphadeno- pathy was 19.4 cases per 100 men per year of follow-up. In addition, four cases of AIDS developed, resulting in an estimated rate of 1.4 cases per 100 male sexual contacts per year since last sexual contact. Progressive deterioration in immune function through various stages of the disease was observed by comparing seronegative subjects with asymptomatic seropositive subjects and with seropositive subjects with lymphadenopathy. The authors suggest that a preexisting immune system depression is not necessary for the ultimate development of AIDS or ARC once an individual has been exposed to the infection. If such were the case, then those not yet infected with the virus should display immune system abnormalities that are like those reported for fully manifest AIDS but less severe. Seronegative individuals in this study showed immune function well within the normal range. 3C-Coa-4 Method: Sample Size: Policy Keys: In this ongoing prospective cohort study, subjects were given an extensive interview-administered questionnaire, a medical history and physical examination by the project physician, and a battery of immuno- logic tests every 3 months. Specimens of blood serum, saliva, urine, semen, and feces were collected each visit. Monitoring will continue for a minimum of 3 years from the date of last sexual contact with the primary case for each cohort member. The cohort was observed specifically for development of antibody to HTLV-III and development of AIDS or ARC symptoms. Between July 1984 and July 1985, 248 homosexual or bisexual males who had had at least one sexual contact with a man with either AIDS or ARC (the primary case) within | year of the onset of the primary case's disease participated in this Toronto study. Of these, 127 were contacts of AIDS patients and 121 were contacts of ARC patients. The mean age of cohort members was 32.5 years, and 94% were white. The majority had sexual contacts with other men as well during the period of sexual relationship with the corresponding primary case. 1) Disease Stages: Progression, Infectivity (IIIC), 2) Populations: Homosexuals (IA1) Author(s): Title: Source: Institution: Findings: Method: Stevens, Cladd E., MD; Taylor, Patricia E., PhD; Zang, Edith A., PhD; Morrison, John M., MA; Harley, Edward J., MS; Rodriguez de Cordoba, Santiago, PhD; Bacino, Carlos, MD; Ting, Robert C.Y., PhD; Bodner, Anne J., PhD; Sarngadharan, M.G., PhD; Gallo, Robert C., MD; Rubinstein, Pablo, MD. Human T-Cell Lymphotropic Virus Type III Infection in a Cohort of Homosexual Men in New York City. Journal of the American Medical Association, 25 April 1986, Vol. 255, No. 16: 2167-2172. Wolf Szmuness Laboratory of Epidemiology (Stevens, Taylor, Zang, Morrison, Harley), and Laboratory of Immunogenetics (Rodriguez de Cordoba, Bacino, Rubinstein), Lindsley F. Kimball Research Institute, New York Blood Center, New York; Biotech Research Laboratories, Inc., Rockville, Maryland (Ting, Bodner); Litton Bionetics, Inc., Kensington, Maryland (Sarngadharan); National Cancer Institute, Bethesda, Maryland (Gallo). Blood samples from a cohort of homosexual men in New York who had participated in 1978 studies of the hepatitis B virus (HBV) or a hepatitis B vaccine were tested for antibody to human T-cell lymphotropic virus type lI (HTLV-III) to examine the relationship between the duration of infection and its immunologic consequences. Sera collected in 1978 or 1979, between 1979 and 1984, and in 1984 were tested. The prevalence of HTLV-II antibody was 6.6% in sera from 1978 or 1979, with a subsequent annual incidence of seroconversion among susceptible men of between 5.5% and 10.6%. Incidence was highest in later years, despite a reported decline In sexual activity by participants. HTLV-II antibody was significantly related to receptive anal intercourse, douching, rectal bleeding, sexual contact with a person known to have AIDS, intravenous drug use, and frequency of contact with a person with AIDS. Lower helper/suppressor T-cell ratios were found in men infected earlier. In the year and a half since the study began, 10 men have developed AIDS. None of the men known to have been antibody positive for less than 4 years has developed AIDS. The authors state that a continuing occurrence of new HTLV-II infections, despite considerable curtailment of homosexual activity, would imply that the risk of exposure from a sexual encounter is now much greater than it was early in the epidemic, and indicates that precautions taken by many homosexual men thus far are not adequate to prevent transmission. Further data are needed to describe the long-term risk for developing AIDS, the rate of progression to AIDS, and whether viral factors and host or environmental cofactors affect progression. Volunteers from a previous study of HBV were sought in 1984 for a prospective epidemiologic study of AIDS involving testing of sera collected every 3 to 6 months from 1978 or 1979 to 1984, except for 166 men from whom specimens were collected only in 1978 or 1979 and in 1984. Participants completed a self-administered questionnaire detailing their medical history, sexual activity, use of recreational drugs, and known contact with AIDS «cases. Physical examination for 3C-Ste-5 Sample Size: Policy Keys: lympadenopathy and signs of AIDS were performed by a physician's assistant. A cohort of 378 homosexual men who have resided in New York City since the AIDS epidemic began was examined in this study. Participants were volunteers, all of whom participated in earlier studies in 1978 or 1979. 1) Incubation Period and Disease Stages (IIIC), 2) Transmission: Sexual Activity (IIA) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Coleman, Diana Lewis, MD; Luce, John M., MD; Wilber, Judith C., PhD; Ferrer, Jose J., MD; Stephens, Boyd G., MD; Margaretten, William, MD; Wagar, Elizabeth A., MD; Hadley, W. Keith, MD, PhD; Pifer, Linda L., PhD; Moss, Andrew R., PhD; Dodek, Peter M., MD; Levy, Jay A., MD; Murray, John F., MD. Antibody to the Retrovirus Associated with the Acquired Immuno- deficiency Syndrome (AIDS): Presence in Presumably Healthy San Franciscans Who Died Unexpectedly. Archives of Internal Medicine, April 1986, Vol. 146, No. 4: 713-715. Departments of Medicine (Coleman, Luce, Dodek, Levy, Murray), Laboratory Medicine (Wagar, Hadley), Pathology (Margaretten), and Epidemiology and International Health (Moss), San Francisco General Hospital and University of California, San Francisco; Coroner's Office (Ferrer, Stephens), and Department of Public Health Virology Laboratory (Wilber), City and County of San Francisco; Department of Pediatrics, University of Tennessee Center for the Health Sciences, Memphis, Tennessee (Pifer). Autopsies and serologic tests were performed on 189 subjects with no history of immunosuppression who died unexpectedly (e.g., suicide, drug overdose, heart attack, homicide). Forty-eight of the 88 single men for whom addresses were available lived in areas of San Francisco with a high incidence of AIDS. In addition, 36 of the subjects were intravenous drug abusers. Antibody to the AIDS-associated retrovirus (ARV) was present in 23 of the 121 (18%) subjects whose sera were tested. However, neither pathologic nor laboratory manifestations of AIDS were present in any of the 189. Based on the estimate that 5% to 20% of persons with antibody to ARV develop AIDS over a 5-year period, only 1 to 5 of the 23 ARV-positive subjects would be expected to have manifest subclinical AIDS. It is possible that this study missed subclinical AIDS because of the relatively small study population. Alternatively, the infectious and neoplastic complications of AIDS, from which the clinical syndrome is diagnosed, may have either a short or no subclinical phase. Blood samples for serologic studies were obtained from either peripheral vessels or the hearts of cadavers. Antibody to ARV was measured In serum samples that were heat inactivated and then reacted with HUT-78 cells infected with the ARV-2 isolate, using an indirect “immunofluorescent assay. All autopsies were performed in accordance with the standards of the National Association of Medical Examiners. Special attention was paid to abnormalities suggestive of AIDS or AIDS- related conditions, including lymphadenopathy, Kaposi's sarcoma, primary lymphomas of the brain, and opportunistic infections such as Pneumocystis carinii pneumonia. A total of 1,114 autopsies were performed at the San Francisco coroner's office from 23 March to 30 November 1983. A subset of 200 met the following criteria: between 20 and 50 years old, lived in the San Francisco metropolitan area, had died within 72 hours of an acute trauma, had not received corticosteroids or other immunosuppressive 3C-Col-6 Policy Keys: drugs, had not received an organ transplant, were not known to have suffered from AIDS, and had not resided in a nursing home or chronic care facility. Of these 200, 189 (152 men and 37 women) with a mean age of 34.6 years were selected for this study. 1) Disease Stages (IIIC), 2) Geographic Trends: San Francisco (IB1) Author(s): Titles Source: [nstitution: Findings: Method: Sample Size: Melbye, Mads, MD; Biggar, Robert J., MD; Ebbesen, Peter, MD; Neuland, Carolyn, PhD; Goedert, James J., MD; Faber, Viggo, MD; Lorenzen, Ib, MD; Skinhoj, Peter, MD; Gallo, Robert C., MD; Blattner, William A., MD. Long-Term Seropositivity for Human T-Lymphotropic Virus Type III in Homosexual Men without the Acquired Immunodeficiency Syndrome: Development of Immunologic and Clinical Abnormalities: A Longitudinal Study. Annals of Internal Medicine, April 1986, Vol. 104, No. 4: 496-500. Institute of Cancer Research, Radiumstationen, Aarhus; Department of Infectious Diseases and Department of Medicine, Rigshospitalet, Copenhagen; Department of Immunology and Rheumatic Diseases, Hvidovre Hospital, Hvidovre, Denmark; Environmental Epidemiology Branch, National Cancer Institute; Department of Pathology, Uniformed Services University of Health Sciences; Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland. To evaluate the long-term effects of HTLV-III seropositivity, longitudinal studies were carried out on a cohort of initially healthy Danish homosexual men. The relative risk of having an abnormal helper/sup- pressor T-cell ratio rose from 14.3-fold among short-term seropositive subjects (less than 19 months) to 46.9-fold among long-term seropositive subjects (greater than 29 months), in comparison with the risk among seronegative subjects. Overall, 91.7% of long-term seropositive men had abnormal T-cell ratios, compared with 12.9% of seronegative men. None of the seropositive men who developed abnormal T-cell ratios reestab- lished normal ratios. Among seropositive men, lymphadenopathy was a highly significant short-term as well as long-term consequence, whereas diarrhea, oral thrush, and herpes zoster (shingles) were correlated with long-term seropositivity. Overall, 50% of long-term seropositive subjects developed at least one of five clinical symptoms, compared with 16% of seronegative men. The authors conclude that a high proportion of persons Infected with HTLV-II will in time develop measurable immunologic and clinical abnormalities. This was a case-control study with long-term (3-year) follow-up, including immunologic studies and diagnosis of clinical symptoms. Antibodies to HTLV-IIl were measured by enzyme-linked immunosorbent assay with a sample-to-control ratio of 5 or greater considered positive. All borderline samples (3.0 to 5.0) were retested by Western blot. Lymphocyte subpopulations were determined by fluorescence with OKT# and OKT8 monoclonal antibodies. A cohort of 250 homosexual men in Denmark, who were initially healthy, volunteered for this study in 1981. The men were recruited through a 3C-Mel-7 mailing to members of a nationwide organization for homosexuals. Of the group, two-thirds were from Copenhagen and one-third from the smaller port city of Aarhus. Policy Keys: 1) Disease Stages (lIIC), 2) Precursors of AIDS (IIIB), 3) Populations: Homosexuals (IA 1), 4) Geographic Trends: Europe (Denmark) (IB4) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Taylor, Jeremy; Afrasiabi, Rahmat; Fahey, John L.; Korns, Elizabeth; Weaver, Michael; Mitsuyasu, Ronald. Prognostically Significant Classification of Immune Changes in AIDS with Kaposi's Sarcoma. Blood, March 1986, Vol. 67, No. 3: 666-671. Center for Interdisciplinary Research in Immunology and Disease, Department of Microbiology and Immunology, and Division of Hematology-Oncology, Department of Medicine, University of California School of Medicine; Division of Biostatistics, University of California School of Public Health, Los Angeles, California. Sixteen immunologic parameters were assessed for their value in providing an immunologically based and prognostically significant classification of the immune alteration in 97 patients with AIDS and Kaposi's sarcoma (AIDS-KS). Reduction in the helper T-cell subpopulation and the helper/suppressor (T4/T8) T-cell ratio were found to correlate most closely with prognosis. T4 lymphocyte levels above 300 ul and a T4/T8 ratio greater than 0.5 indicated a relatively good prognosis, 85% to 95% survival at 12 months. T4 levels below 100 ul and/or a T4/T8 ratio of less than 0.2 was associated with a very poor prognosis, less than 25% survival at 12 months. These immunologic findings were found to have independent prognostic value compared with disease classification based on clinical status or KS tumor stage. Reduction in T4 cell levels below the normal range was characteristic of AIDS-KS but was not sufficient to establish prognosis. The lowest 5% of the range of values for a normal population is more than three times greater than the critical value seen for poor prognosis in this study. Other measures that correlated with prognosis were reduced prolifera- tive capacity, increased OKTI10 antigen expression, and elevated levels of serum immunoglobulin A and immune complexes. Changes that frequently occurred in AIDS-KS but did not have prognostic significance were elevated levels of serum immunoglobulin G, cellular HLA-DR expression, and skin test anergy. Clinical and immunological assessment of each patient was performed initially and at 3-month intervals, whenever possible, between January 1982 and April 1985. Blood tests were performed for total T4 cell number, total T8 cell number, T4/T8 ratio, HLA-DR and OKT10 antigen expression, measurement of serum immunoglobulins G, A, and M and immune complexes, skin sensitivity testing, FcR cell tests, and natural killer cell activity. The study group consisted of 97 consecutive patients with biopsy-proven epidemic KS seen at the UCLA Kaposi's Sarcoma Clinic between January 1982 and February 1984 whose clinical and immunologic status could be clearly determined. All patients were male homosexuals whose median age was 36 years (range, 27 to 64 years). There were no Haitians, Africans, or blood transfusion recipients among these patients. In April 1985, 37 patients were still alive, 55 had died, and 5 were lost to follow- 3C-Tay-8 up. By June 1984 all but 25 had received some sort of therapy, such as alpha interferon treatment, chemotherapy, or bone marrow transplants. The median time of follow-up was 12 months (range, | to 33 months). Policy Keys: 1) Disease Stages (Prognosis) (IIIC), 2) Immunological Aspects (IIE), 3) Populations: Homosexuals (IA1) Author(s): Title: Source: Institution: Findings: Method: Coutinho, R.A.; Krone, W.J.A.; Smit, L.; Albrecht-van Lent, P.; van der Noordaa, J.; Schaesberg, W.; Goudsmit, J. Introduction of Lymphadenopathy Associated Virus or Human T Lymphotropic Virus (LAV/HTLV-III) into the Male Homosexual Community in Amsterdam. Genitourinary Medicine, 1986, Vol. 62: 38-43. Municipal Health Service, Department of Infectious Diseases (Coutinho, Albrecht-van Lent); Department of Virology, Academic Medical Centre (Krone, Smit, van der Noordaa, Goudsmit), and Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (Schaesberg), Amsterdam, the Netherlands. To establish when human T-cell lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV) was introduced into the Netherlands, this study examined a cohort of 685 homosexual men who had participated in a hepatitis B vaccine program between 1980 and 1982. On entry into this study, 5 of the 685 participants were found to have HTLV-II antibodies. During follow-up 15 others were detected among the 680 who Initially tested HTLV-III antibody negative. HTLV- [II/LAV was not transmitted by the hepatitis vaccine used in the previous study. Anal sexual contact and antibodies to cytomegalovirus were found to correlate with the presence of HTLV-III/LAV antibody. Six of the 15 men who converted to positive during the study period reported a mononucleosislike illness, and three of these had other concurrent viral infections. As of study completion, only | of the 20 antibody-positive men had developed AIDS, 3 years after conversion to HTLV-II antibody-positive status. These findings suggest that the incubation period of AIDS in homosexual men can be at least 3 years from seroconversion and that during that period patients may be largely without symptoms. The authors conclude that HTLV-III/LAV was introduced into the Dutch male homosexual population in the late 1970s, a few years before the first case of AIDS appeared in a native Dutchman. Baseline data about each participant's medical history and lifestyle, including duration (in years) of sexual activity and number of partners, were obtained by interview on entry into the vaccine study. (Active and passive anal intercourse were not differentiated.) Blood samples were collected at monthly intervals during the first 5 months and every 3 months thereafter, and participants were asked whether they had had any symptoms during the preceding period. The first and last blood samples of the participants were tested for the presence of antibodies to LAV/HTLV-III. If seroconversion was found, all intervening blood samples were tested. Seroconversion was confirmed by at least two sequential blood samples and by Western blotting analysis. Actuarial methods were used to calculate the life table attack rate, and the association between potential risk and seropositivity or 3C-Cou-9 Sample Size: Policy Keys: seroconversion for LAV/HTLV-III was studied by stepwise logistic regression. A cohort of 685 Dutch homosexual men who participated in a placebo- controlled efficacy trial of a heat-inactivated hepatitis B vaccine and who lived in and around Amsterdam were selected for the study. The vaccine study from which the cohort was selected started in November 1980; participants could enter it until 31 December 1981, and follow-up continued until the end of 1982. 1) Incubation Period and Disease Stages (IIIC), 2) Geographic Trends: Europe (Holland) (IB4), 3) Populations: Homosexuals (IA1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Biberfeld, Peter; Porwit-Ksiazek, Anna; Bottiger, Blenda; Morfeldt- Mansson, Linda; Biberfeld, Gunnel. Immunohistopathology of Lymph Nodes in HTLV-II Infected Homosexuals with Persistent Adenopathy or AIDS. Cancer Research, September 1985, Vol. 45 (Suppl.): 4665s-4670s. Department of Pathology, Karolinska Institute and Hospital (P. Biberfeld, Porwit-Ksiazek); Department of Immunology, National Bacteriology Laboratory (Bottiger, G. Biberfeld); Department of Infectious Diseases, Roslagstulls Hospital (Morfeldt-Mansson), Stockholm, Sweden. This study was analyzed and attempted to systematize cellular changes in lymph nodes associated with the progression of AIDS. Of the lymph node biopsies studied, all AIDS patient biopsies (except one with Kaposi's sarcoma) had the same histopathological pattern of follicular depletion. The lymphadenopathy biopsies showed a spectrum of changes: follicular hyperplasia, involution with follicular fragmentation, or involution with follicular atrophy. Immunohistology showed a temporal and structural relation between follicular involution, disappearance of follicular dendritic cells (nerve cell branches in the follicles), and follicular invasion by T cells. These results indicate elimination of dendritic reticulum cells as part of a pathogenic mechanism in follicular involution. Anglogenesis (development of blood vessels) was found to be increased in many biopsies in stages of involution and depletion. Also noted were marked changes not only in T cells, but in the B-cell compartment of patients with lymphadenopathy or AIDS. Results indicate the possibility of staging lymph nodes by combined histopathology and immunohistology; this may improve the evaluation of prognosis for these patients. Results also indicate that angiogenesis may be important in the initiation of Kaposi's sarcoma. Lymph node biopsies were studied for histopathology, immunohistology, and T-cell subsets in cell suspensions. Frozen sections of tissue were immunostained and examined microscopically. Cell suspensions were studied for reactivity to a panel of monoclonal antibodies. Antibodies to human T-cell lymphotropic virus type III (HTLV-II) were demonstrated by a dot immunobinding assay and by enzyme-linked immunosorbent assay. Lymph node biopsies from 43 male Swedish homosexuals with lymph- adenopathy and 10 male homosexual AIDS patients were studied. All participants tested seropositive for HTLV-III antibody. 1) Disease Stages (IIIC), 2) Immunological Aspects (IIE), 3) Precursors of AIDS (IIIB) 3C-Bib-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jeffries, Eric, MB, MPH, FRCPC; Willoughby, Brian, MD, CCFP; Boyko, William J., MD, FRCPC; Schechter, Martin T., MD, MSc, PhD; Wiggs, Barry, MSc; Fay, Sean, MB; O'Shaughnessy, Michael, PhD. The Vancouver Lymphadenopathy-AIDS Study: 2. Seroepidemiology of HTLV-III Antibody. Canadian Medical Association Journal, 15 June 1985, Vol. 132: 1373- 1377. St. Paul's Hospital and the University of British Columbia, Vancouver (Jeffries, Willoughby, Boyko, Schechter, Wiggs, Fay); Division of Viral Studies, Laboratory Centre for Disease Control, Department of National Health and Welfare, Ottawa, Canada (O'Shaughnessy). This study reports the prevalence of human T-cell lymphotropic virus type III (HTLV-II) antibody and behavioral risk factors for seropositivity In a group of homosexual men recruited from primary-care practices. Testing for antibody to HTLV-III was carried out for 448 participants in the Vancouver Lymphadenopathy-AIDS Study. The overall prevalence rate of seropositivity to HTLV-II was 34%. Of 130 seronegative subjects followed for an average of 8.5 months, 14 became seropositive. More than 100 male lifetime sexual partners, frequent receptive anal intercourse, "fisting," a history of gonorrhea or hepatitis, and frequent sexual contact in clubs were found to be independent risk factors for HTLV-III seropositivity. The subjects completed a questionnaire and underwent a physical exam and lab testing on two occasions at least 3 months apart. Testing for HTLV-II antibody was done by enzyme-linked immunosorbent assay; equivocal results were retested by the Western blot technique. Various statistical techniques were used to account for the effects of the variables such as sexual contact in other cities, illicit drug use, and fisting. Findings are reported for patients and controls. This study reports on 448 participants for whom data were available from 726 homosexual men who were recruited from six general practices in central Vancouver between November 1982 and February 1984. The following case-control definitions were used: the cases were participants who were HTLV-II positive at the time of either visit, and the controls were participants who were HTLV-III negative at the time of the first visit and, if completed, the second visit. 1) Incubation Period and Disease Stages (IIIC), 2) Transmission: Sexual Activity (IIA), 3) Cofactors: Demographic Status, Other Infections (IC1,3), 4) Populations: Homosexuals (IAl), 5) Geographic Trends: Canada (IB1) 3C-Jef-11 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Jaffe, Harold W., MD; Feorino, Paul M., PhD; Darrow, William W., PhD; O'Malley, Paul M., BA; Getchell, Jane P., DrPH; Warfield, Donna T., BS; Jones, Bonnie M., BS; Echenberg, Dean F., MD, PhD; Francis, Donald P., MD; Curran, James W., MD. Persistent Infection with Human T-Lymphotropic Virus Type [II/Lymphadenopathy-Associated Virus in Apparently Healthy Homo- sexual Men. Annals of Internal Medicine, May 1985, Vol. 102, No. 5: 627-628. Centers for Disease Control, Atlanta, Georgia; Department of Public Health, San Francisco, California. The natural history of infection with human T-cell lymphotropic virus type IlI/lymphadenopathy-associated virus (HTLV-III[/LAV) was examined in this study of l4 apparently healthy homosexual men with serologic evidence of HTLV-III/LAV infection to determine the duration of their seropositivity, their immunologic status, and the frequency of isolation of HTLV-III/LAV from their peripheral blood. The estimated duration of seropositivity ranged from 4 to 69 months (median, 33 months). Eleven men had helper/suppressor T-cell ratios below 1, the lower limit of normal for the study. Low ratios were significantly related with duration of seropositivity. HTLV-II/LAV was isolated from blood samples of 8 of 12 men; bacteria were found in cultures of the other 2 men. The culture-positive and culture-negative subjects did not differ significantly in age, presence of a palpable lymph node, T-cell ratio, or duration of seropositivity. The two men who had been seropositive for more than 5 years had positive cultures. Study findings suggest that some seropositive men may remain asymptomatic for at least 5 years and that persistent infection may be common among asymptomatic seropositive persons at risk for AIDS. This study involved testing sera for antibody to HTLV-III/LAV. Sera were collected from subjects during studies conducted between 1978 and 1980, at subsequent clinic visits, and from the same individuals between 1983 and 1984. Serum samples were tested by enzyme-linked immuno- sorbent assay, and equivocal cases were retested with a Western blot assay. The date of seroconversion was defined as the midpoint between the date that the last negative specimen was drawn and the date of the first positive specimen. Lymphocytes collected at the patient's most recent clinic visit were tested for the helper/suppressor T-cell ratio and cultured to isolate HTLV-III/LAV. Fourteen homosexual men who were seropositive for HTLV-III/LAV and did not have AIDS, signs or symptoms suggestive of the prodrome, or laboratory evidence of anemia or leukopenia were randomly selected from a sample of 975 homosexual men who had been sought to partici- pate in a follow-up study of AIDS. The 975 men were randomly selected 3C-Jaf-12 Policy Keys: from a cohort of 6,875 homosexual men who between 1978 and 1980 attended the San Francisco City Clinic, a facility for treatment of sexually transmitted diseases, and were enrolled in studies of hepatitis B virus. 1) Incubation Period and Disease Stages (IIIC), 2) Populations: Homosexuals (IA1), 3) Precursors of AIDS (IIIB) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Eyster, M. Elaine, MD; Goedert, James J., MD; Sarngadharan, M.G., PhD; Weiss, Stanley H., MD; Gallo, Robert C., MD; Blattner, William A., MD. Development and Early Natural History of HTLV-II Antibodies in Persons with Hemophilia. Journal of the American Medical Association, 19 April 1985, Vol. 253, No. 15: 2219-2223. Division of Hematology, The Milton S. Hershey Medical Center of the Pennsylvania State University, Hershey, Pennsylvania (Eyster); Environmental Epidemiology Branch (Goedert, Weiss, Blattner) and the Laboratory of Tumor Cell Biology (Gallo), National Cancer Institute, Bethesda, Maryland; Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland (Sarngadharan). This study investigated the latency period between exposure to human T- cell lymphotropic virus type III (HTLV-II) and disease manifestation through examination of serological evidence of HTLV-III infection in stored sera from a cohort of recipients of factor VIII concentrate followed up for a period of 3 to 9 years. Antibodies to HTLV-III were first detected in 1979 in a cohort of known hemophiliacs, over half of whom seroconverted in 1981-82. Lymphadenopathy was present in 70% who tested positive to HTLV-II for more than 3 years, compared with 10% of those who had been seropositive for 3 years or less. Helper T-cell counts were low in those who tested positive to HTLV-III early on but normal in those who were seropositive later. The authors suggest that the long latency period after the appearance of HTLV-III antibodies may indicate an ongoing process rather than an acute infection. Blood sera from hemophiliacs using factor VIII were tested retrospec- tively for HTLV-II antibodies, and the patients were observed for evidence of lymphadenopathy. Stored (frozen) serum samples were tested in a double-blind fashion by enzyme-linked immunosorbent assay, with selected cases reevaluated by the Western blot technique. Compre- hensive evaluations were performed for patients at clinic visits after September 1982, including a medical history, physical exam, complete blood cell count with differential, and platelet count. T-cell subset counts were done by immunofluorescence with antibodies to Leu3 and Leu2 as markers. A group of 30 hemophiliacs was selected from a cohort of 69 recipients of factor VIII concentrate, of whom 52 were seropositive for HTLV-III antibodies in 1983-84. The group of 30 was selected because multiple stored blood samples were available to be tested. 1) Incubation Period and Disease Stages (IIIC), 2) Populations: Hemophiliacs (IA3) 3C-Eys-13 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lane, H. Clifford, MD; Masur, Henry, MD; Gelmann, Edward P., MD; Longo, Dan L., MD; Steis, Ronald G., MD; Chused, Thomas, MD; Whalen, Gail, BS; Edgar, Lynn C., MS; Fauci, Anthony S., MD. Correlation Between Immunologic Function and Clinical Subpopulations of Patients with the Acquired Immune Deficiency Syndrome. The American Journal of Medicine, March 1985, Vol. 78: 417-422. Laboratory of Immunoregulation and the Laboratory of Microbial Immunity, National Institute of Allergy and Infectious Diseases; Critical Care Medicine Department, Clinical Center; Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. This study was designed to determine whether there was a significant correlation between the clinical presentation of patients with AIDS or AIDS-related illnesses and the degree of their underlying immune system abnormalities. Patients with AIDS with opportunistic infections were the most severely immunologically compromised of all groups studied (including AIDS patients with Kaposi's sarcoma alone), especially in numbers of lymphocytes (white blood cells) and total number of helper T cells. Patients with AIDS as a group (including patients with opportunistic infections, Kaposi's sarcoma, and chronic lymphadenopathy) had significantly lower mean values for all immunologic variables except total suppressor T cell number. These findings confirm previous studies which found that the absolute number of helper T cells is the more accurate predictor of overall immune function for AIDS patients than the helper/suppressor T-cell ratio. Results suggest that patients initially presenting with opportunistic infections may be in a later, more severely immunodeficient phase of the AIDS spectrum. Blood specimens were obtained from subjects and analyzed for various immunologic indicators. Absolute numbers of helper and suppressor T cells were determined by multiplying the total lymphocyte count (determined by the total white cell count and differential) by the percentages of lymphocyte staining with the appropriate (OKT4 or OKT) monoclonal antibody. The patient group consisted of 38 male patients who were referred to the National Institutes of Health for evaluation of possible AIDS. Of these patients, 17 had experienced serious opportunistic infections, 12 had Kaposi's sarcoma, and 9 had chronic lymphadenopathy. Patients ranged in age from 19 to 55 years. All but two were homosexual. The control groups consisted of 38 age-matched hospital personnel and 10 healthy homosexual men. 1) Disease Stages (IIIC), 2) Immunological Aspects (IIE), 3) Clinical Manifestations: Kaposi's Sarcoma, Opportunistic Infections (IIIA 1,2) 3C-Lan-14 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Hersh, Evan M.; Mansell, P.W.A.; Reuben, J.M.; Rios, A.; Newell, G.R. Immunological Characterizations of Patients with Acquired Immune Deficiency Syndrome, Acquired Immune Deficiency Syndrome-Related Symptom Complex, and a Related Life-Style. Cancer Research, December 1984, Vol. 44: 5894-5901. Departments of Clinical Immunology and Biological Therapy (Hersh, Mansell, Reuben, Rios), Laboratory Medicine (Hersh, Reuben), and Cancer Prevention (Mansell, Rios, Newell), The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, Texas. This study investigated the presence of risk factors, including lifestyle, and predisposition to immune deficiency. Asymptomatic homosexuals, referred because they were concerned that their lifestyle might eventuate AIDS, showed definable immunodeficiency consistent with that seen In a more severe form in AIDS. All patients had elevated serum thymosin levels, suggesting an early relationship with the syndrome. In patients with more advanced disease (AIDS or AIDS-related complex, ARC), indicators of immunological and hematological functions tended to worsen. A number of hematological, chemical, and immunological parameters in patients with AIDS or its prodrome and in symptom-free subjects with a high-risk homosexual lifestyle were significantly abnormal in asymptomatic cases and even worse in the other two groups. Findings for several parameters were equally abnormal in all three groups. One parameter (serum interferon levels) was abnormal only in patients with Kaposi's sarcoma and/or opportunistic infection. Study results define the spectrum of disease quantitatively and provide a data base for studies on pathogenesis and prognosis and for targeting and monitoring therapeutic approaches. Case-control comparisons were presented in this study. All cases were evaluated by a complete history, physical examination, detailed lifestyle questionnaire, and standard medical and immunological tests. Controls were evaluated concurrently. Patient groups were classified as asymptomatic, symptomatic (ARC), and Kaposi's sarcoma/opportunistic infections (AIDS), and they were compared with normal controls. The study group consisted of 135 male homosexuals referred by their physicians to the AIDS clinic at the M. D. Anderson Hospital in Houston, Texas, 28 of whom were symptom free, 74 of whom had ARC, and 33 of whom had AIDS. Patients were referred to the clinic because either AIDS or ARC was suspected or because the patient, knowing the suspected relationship between AIDS and lifestyle, requested referral. Controls consisted of heterosexual male and female hospital employees, faculty, and medical or graduate students in the same age range as the patients. 1) Disease Stages (IIIC), 2) Immunological Aspects (IIE) 3C-Her-15 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Moss, Andrew R., PhD; McCallum, Gerald, MD; Volberding, Paul A., MD; Bacchetti, Peter, MS; Dritz, Selma, MD. Mortality Associated with Mode of Presentation in the Acquired Immune Deficiency Syndrome. Journal of the National Cancer Institute, December 1984, Vol. 73, No. 6: 1281-1284. Department of Epidemiology and International Health, University of California, San Francisco (Moss, Bacchetti); Department of Family and Community Medicine, San Francisco General Hospital and Medical Center (McCallum); Department of Medicine, University of California, San Francisco, San Francisco General Hospital (Volberding); Bureau of Communicable Disease Control, Department of Public Health, City of San Francisco, California (Dritz). This study tracked the survival rates of 165 AIDS patients with Kaposi's sarcoma (KS) or opportunistic infections (Ols) in San Francisco from July 1980 (the first reported AIDS case) through May 1983. Of 75 patients with only KS, the median survival was more than 21 months, longer than the current median survival for patients with KS only. Of 90 patients with Ols, primarily Pneumocystis carinii pneumonia, median survival was 9 months, with no survivors at 21 months. Patients with KS and OI had a survival rate very similar to that of those with only Ol. Of the 75 KS patients, 15 either progressed to OI or had OI listed as the cause of death. Results indicate that OI is a primary problem in KS patients as well as in other AIDS patients and that severity of clinical illness in KS patients may be more important than estimates of tumor dissemination. This population-based study used figures maintained by the Bureau of Communicable Disease Control of the San Francisco Department of Public Health. A total of 165 AIDS patients in San Francisco with either KS or OI or both were studied. 1) Disease Stages (IIIC), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma, Opportunistic Infections (IIIA 1,2) 3C-Mos-16 Author(s): Title: Source: Institution: Findings: Cooper, David A.; Gold, Julian; May, Warwick; Kaminsky, Lawrence S.; Penny, Ronald; Levy, Jay A. Contact Tracing in the Acquired Immune Deficiency Syndrome (AIDS): Evidence for Transmission of Virus and Disease by an Asymptomatic Carrier. The Medical Journal of Australia, 27 October 1984, Vol. 141: 579-582. Centre for Immunology, St. Vincent's Hospital, Darlinghurst, New South Wales and the University of New South Wales (Cooper, May, Penny); Commonwealth Institute of Health, The University of Sydney, Sydney, Australia (Gold); Cancer Research Institute, University of California School of Medicine, San Francisco (Kaminsky, Levy). A bisexual man was the sixth case of AIDS to be reported to the health authorities in Australia. He was the first case who had never traveled outside the country. Five of his six sexual contacts from 1979 to 1984 were traced, and their immunologic and serologic status was studied. Unlike most patients with AIDS reported in the U.S., this patient had relatively few sexual partners. In addition, he did not take recreational drugs and did not have multiple episodes of sexually transmitted diseases, all of which are thought to be risk factors for the development of AIDS among homosexuals in the U.S. Contact A could not be located, but was thought to be healthy and living in northern Australia. Contact with A occurred 2 years before the onset of lymphadenopathy syndrome (LAS). It was known that A had not traveled outside Australia before sexual contact with the patient. However, contact B, with whom the patient had contact 18 months before the onset of LAS, had traveled extensively to the U.S. from 1973 to 1978 and had numerous sexual contacts, including many in bathhouses in San Francisco. Contact D, who had contact with the patient after he developed LAS, was the only other contact who had visited the U.S. Contact B had a history of intermittent diarrhea for several years. No abnormalities were found in physical examinations of contacts B, E, and F, whereas both C and D, who had contact with the patient during the first year of LAS, had evidence of lymphadenopathy. All contacts except E had had multiple episodes of sexually transmitted diseases. Contacts D, E, and F were the only ones without immunologic abnormalities and without positive reactions for antibody to AlDS-associated retroviruses (ARV). A number of epidemiologic, clinical, and laboratory features of this report support the theory that the patient developed his disease from sexual contact with subject B, who had no symptoms. After the patient developed LAS, he had sexual contacts with C, D, E, and F. His female sexual partner (E) and contacts D and F all showed no evidence of exposure (pre-antibody testing) to the disease. Contact C, however, the patient's lover for almost 1 year just after he developed LAS, had severe immunologic abnormalities and serologic evidence of exposure to ARV. The authors suggest that transmission of the AIDS virus may be most 3C-Coo-17 Method: Sample Size: Policy Keys: common during the LAS phase, especially since the patient could be unaware that he may be transmitting a lethal disease. The sexual contacts of an AIDS patient were traced. They were asked to report to the hospital for clinical and laboratory evaluation. Special attention was given to the dates of sexual contact with the patient, symptoms of AIDS, drug use, past sexual and medical history, and overseas travel. Physical examinations were performed, and blood samples were tested for immunologic abnormalities and antibody to ARV. The AIDS patient was a 29-year-old bisexual man who was referred to St. Vincent's Hospital in Sydney, Australia, in October 1983 for evaluation of recurrent episodes of lymphadenopathy since January 1982. Of the six sexual contacts of the AIDS patient, five reported for evaluation on one or two occasions between January and April 1984. All except contact E were men. 1) Incubation Period (IIIC), 2) Transmission: Sexual Activity (IIA), 3) Cofactors: Lack of Multiple Partners (IC1), 4) Geographic Trends: Australia (IB3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Marche, C.; Kernbaum, S.; Saimot, A.G.; Neguesse, Y.; Bouton, C.; Diebold, J.; Regnier, B.; Vittecoq, D. Histopathological Study of Lymph Nodes in Patients with Lymphadenopathy or Acquired Immune Deficiency Syndrome. European Journal of Clinical Microbiology, February 1984, Vol. 3, No. 1: 75-76. Hopital Claude Bernard, Paris, France. Patients with AIDS frequently exhibit enlarged lymph nodes. These patients appear to have lymphadenopathy associated with unexplained fever, sweats and weight loss before full-blown AIDS appears; this has been called lymphadenopathy syndrome (LAS) or pre-AIDS syndrome. The lymph nodes of LAS and AIDS patients were studied to relate structural damage to lymph tissue with clinical and blood antibody data and find prognostic histopathologic characteristics of the disease. These researchers defined four types of lymph node structural abnormalities which correlated with their clinical data. Of 10 patients with LAS, 8 had type I and 2 had type II. From 4 to 5 months later two patients had a second biopsy, and one case had progressed from type I to type II, while the other progressed from type II to an association of type II and IV in the same node and later developed AIDS. Of 13 patients with AIDS, 8 had type III, 3 type IV (Kaposi's sarcoma), and 2 type Il. These researchers believe that these findings might help predict the course of development of LAS and AIDS. (Reviewer note: CD#4+ cells are now used as a less invasive prognostic test.) Since 1980, 27 lymph nodes from 23 patients were studied by histo- pathological sections. Infected lymph nodes were excluded. Four types of diseased tissue were defined. Type [I was lymphoid follicular hyperplasia (a sac of cells from lymph node tissue which have increased in size due to the formation and growth of new cells). This tissue was invaded by various cells, including mature and immature lymph node cells, premature antibody cells, and various types of blood cells, including types of white blood cells. In this type there were areas of lymph node cell death and tissue hardening. Type II was angio-immuno- blastic-lymphadenopathy-like (AIL-like), in which the lymph node structure was changed due to the growth of mixed types of cells with changes in the density of the cell population and at times fibrosis (tissue composed of fibers). Type III was lymph node atrophy, in which the lymph node structure had disappeared and been replaced by fibrous tissue; bacteria or fungi may be present. At times the lymph node was difficult to expose and examine under the microscope. Type IV was represented by Kaposi's sarcoma. Twenty-three patients were studied, 10 patients with LAS and 13 with AIDS. 1) Disease Stages (IIIC), 2) Precursors of AIDS: Lymphadenopathy (IIIB), 3) Geographic Trends: Europe (France) (IB4) 3C-Mar-18 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Joshi, V.V., MD, PhD, MRCPath; Oleske, J.M., MD; Minnefor, A.B., MD; Singh, R., MD; Bokhari, T., MD; Rapkin, R.H., MD. Pathology of Suspected Acquired Immune Deficiency Syndrome In Children: A Study of Eight Cases. Pediatric Pathology, 1984, Vol. 2: 71-87. Departments of Pathology and Pediatrics, Children's Hospital of New Jersey; United Hospitals Medical Center, Newark, New Jersey; St. Michael's Medical Center, Newark, New Jersey; St. Joseph's Hospital and Medical Center, Paterson, New Jersey; University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey. This article describes the possible significance of pathological findings in children with AIDS, in part to distinguish between pediatric and adult cases and to assist in diagnosis of pediatric AIDS. Biopsy or autopsy material from eight New Jersey children with suspected AIDS was studied. One or both parents of each of these children had one or more of the recognized risk factors for AIDS, such as intravenous drug abuse, prostitution, etc. The clinical features included failure to thrive and respiratory symptoms, defective immunity, and absence of any congenital immunodeficiency. Three different microscopic tissue patterns of lymph node abnormality were seen in patients with different clinical disease progressions. The three patterns were (1) normal paracortex with follicle proliferation, (2) depleted paracortex with proliferation of follicles, and (3) atrophy of follicles and depletion of the paracortex. Lymphoid interstitial pneumonitis (LIP), a previously unreported lesion in AIDS, was present in 4 cases. The authors suggest that the different histologic (tissue microstructure) patterns constitute a spectrum and may represent different stages of progression from follicle proliferation to marked depletion of lymph tissues in these children. Findings of pathology may be helpful in diagnosing AIDS in children and in deciding the type of therapy to be given for the pulmonary disease process which is the presenting feature of these children. This study consisted of case reports, including biopsy and/or autopsy results and epidemiologic and laboratory studies. Eight children in New Jersey, aged 7 weeks to 3.5 years, with parents at risk for AIDS were studied. 1) Disease Stages (IIIC), 2) Diagnostic Definitions of AIDS: Diagnostic Indicators (IIIA 3), 3) Populations: Pediatric Cases (IA4) 3C-Jos-19 [II. Characteristics of Disease D. Central Nervous System Disease Infection Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Bishburg, Eliahou, MD; Sunderam, Gnana, MD; Reichman, Lee B., MD, MPH; and Kapila, Rajendra, MD. Central Nervous System Tuberculosis with the Acquired Immunode- ficiency Syndrome and Its Related Complex. Annals of Internal Medicine, August 1986, Vol. 105, No. 2: 210-213. Infectious Diseases and Pulmonary Divisions, Department of Medicine, University Hospital, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey. To aid in diagnosis of central nervous system (CNS) involvement in AIDS, this study reviewed cases of CNS infection with Mycobacterium tuberculosis in 10 patients with AIDS and AIDS-related complex (ARC) who were evaluated for 48 months. Nine patients were intravenous drug abusers, and | was Haitian. All isolates of M. tuberculosis were sensitive to antituberculosis drugs. The patients showed a wide spectrum of clinical presentations (case reports for five are given), including meningitis in two patients, multiple abscesses of the brain in one, and tuberculomas (tuberculosis abscesses or tumors) in four. All three patients with AIDS died of opportunistic infections preceded by CNS tuberculosis. Among the seven patients with ARC, three improved with treatment, three were lost to follow-up, and one died. Because patients with tuberculosis can be cured, biopsy of accessible brain lesions should be mandatory, according to the authors. Records of all patients with AIDS and ARC who were treated at the University Hospital in Newark, New Jersey, from January 1981 to December 1984 were reviewed. Patients with altered mental states, seizures, behavioral abnormalities, or focal neurologic deficits had computed tomographic (CT) scans of the brain, with and without contrast, and cerebrospinal fluid examinations if appropriate. After biopsies of accessible intracranial space-occupying lesions were done, the tissue was examined histologically, and cultures were done for mycobacteria. Antibody to human immunodeficiency virus was tested by enzyme-linked immunosorbent assay and confirmed by Western blot. Approximately 420 patients with AIDS or ARC, 52 of whom had tuberculosis, were treated during the study. The 10 patients with CNS tuberculosis were examined in depth. Three of these 10 had AIDS and 7 had ARC; 6 were men and 4 were women; ages ranged from 19 to 42 years (mean, 33.5). 1) Central Nervous System Disease Infection (IIID), 2) Treatment: Symptom Management (IVB) 3D-Bis-1 Author(s): Title: Source: Institution: Findings: Method: Navia, Bradford A., MD; Jordan, Barry D., MD; Price, Richard W., MD. The AIDS Dementia Complex: I. Clinical Features. Annals of Neurology, June 1986, Vol. 19, No. 6: 517-524. Departments of Neurology, Memorial Sloan-Kettering Cancer Center; The New York Hospital; Cornell University Medical College, New York, New York. Seventy AIDS patients at New York hospitals were studied for clinical manifestations of AIDS-related dementia. Of these, 46 (45 males, | female) suffered unexplained, progressive dementia, which represented a major aspect of their illness. No neurological impairment could be attributed to psychotropic medication. The duration of AIDS (from diagnosis to death) was a median of 8 months in the demented group and a median of 5 months in the nondemented group. Of systemic diseases, 25 (54%) of the demented group had opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium- intracellulare, cytomegalovirus); opportunistic infections occurred in 11 (46%) of the nondemented group. Nineteen (41%) of the demented group had opportunistic infections and Kaposi's sarcoma, while only nine (38%) of the nondemented group were afflicted with both. None of the demented group had Kaposi's sarcoma alone, while three (13%) of the nondemented group had only Kaposi's sarcoma. Of the demented group, 29 had AIDS before the dementia, 6 had dementia at the time of AIDS diagnosis, and Il had dementia before AIDS. Of these 11, dementia was the only AIDS manifestation in 4. Of these, three were found to have opportunistic infections at autopsy. The most common early manifestations of dementia were impaired memory, concentration, and motor functions. In almost one-half of the demented group, either motor disturbance or behavioral disturbance predominated. The disease progressed steadily in most patients. In the advanced stage of dementia, patients exhibited a typical picture of severe dementia: mutism, incontinence, paraplegia (paralysis in two limbs), and in some cases myoclonus (rapid muscle spasms). The high incidence and unique clinical aspects of AIDS-related dementia indicate a direct brain infection by the retrovirus that causes AIDS. The authors recommend that this disorder, currently referred to as subacute encephalitis (inflammation of the brain) or subacute encephalopathy (brain disease), be named AIDS dementia complex. Over a period of nearly 3 years, 70 AIDS patients were seen in neurological consultations at Memorial and New York hospitals. Patients' clinical records were also reviewed, with emphasis on neurological symptoms, general background history, and other manifestations of AIDS. This group was selected from a group of 121 patients with AIDS who were examined neuropathologically at autopsy at these facilities. 3D-Nav-2 Sample Size: Policy Keys: The study sample included 70 AIDS patients: 46 (45 males and | female) with progressive dementia, and 24 males without dementia. Both groups had a mean age of 40. The demented group contained 38 homosexuals and bisexuals, 5 intravenous (I.V.) drug abusers, 2 homosexual/I.V. drug abusers, and 1 of unknown status. The nondemented group contained 22 homosexuals and bisexuals, | homosexual/l.V. drug abuser, and | of unknown status. 1) Central Nervous System Disease Infection (IID), 2) Diagnostic Definitions of AIDS: Opportunistic Infections, Kaposi's Sarcoma (IlIA2,1) Author(s): Title: Source: Institution: Findings: Method: Sample: Policy Keys: Sharer, Leroy R., MD; Epstein, Leon G., MD; Cho, Eun-Sook, MD; Joshi, Vijay V., MD; Meyenhofer, Markus F.; Rankin, Linda F., MD; Petito, Carol K., MD. Pathologic Features of AIDS Encephalopathy in Children: Evidence for LAV/HTLV-III Infection of Brain. Human Pathology, March 1986, Vol. 17, No. 3: 271-284. Departments of Pathology (Sharer, Cho, Joshi), Neurosciences (Epstein), Pediatrics (Joshi, Epstein), and Anatomy (Meyenofer), University of Medicine and Dentistry of New Jersey - New Jersey Medical School, Newark, New Jersey; Department of Pathology, St. Joseph's Hospital, Paterson, New Jersey (Rankin); Department of Pathology, Cornell University Medical College, New York, New York (Petito). This study reports neuropathologic findings in 11 children with a new AIDS-related central nervous system (CNS) disorder. The children all died of AIDS complicated by progressive encephalopathy (brain disease). Ten of the children either had antibodies to human T-cell lymphotropic virus type III (HTLV-II) or had received blood products from donors later found to be antibody positive. At autopsy, the brains of these children revealed a unique constellation of findings, including diminished brain weight in all cases, with cerebral atrophy in the most marked of these cases. In addition, inflammatory cell infiltrates were seen in nine brains, multinucleated (having more than one nucleus) cells in eight, vascular calcification (hardening) in ten, vascular and perivascular inflammation in five, and white-matter changes in nine. This was a neuropathologic study involving autopsy of the brains of pediatric AIDS cases. In addition, serum HTLV-III antibody testing was performed either by an enzyme-linked immunosorbent assay or by Western blot technique. Eleven children with AIDS-related CNS disorders were autopsied. They ranged in age from 4 months to 11 years. All of the patients had at least one risk factor for AIDS, and three patients had two risk factors. In seven cases the risk factor involved the mother, who was either an intravenous drug abuser (five cases) or Haitian (two cases); in three of these seven cases the mother died of AIDS. Three patients had received blood products from donors who were later found to have antibody to HTLV-III. Serum antibody to HTLV-III was present in all of the children who were tested (8 of 11). I) Central Nervous System Disease Infection (IID), 2) Populations: Pediatric Cases (IA4) 3D-Sha-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Navia, Bradford A., MD; Petito, Carol A., MD; Gold, Jonathan, W.M., MD; Cho, Eun-Sook, MD; Jordan, Barry D., MD; Price, Richard W., MD. Cerebral Toxoplasmosis Complicating the Acquired Immune Deficiency Syndrome: Clinical and Neuropathological Findings in 27 Patients. Annals of Neurology, 1986, Vol. 19: 224-238. Departments of Neurology (Navia, Jordan, Price), Pathology (Petito), and Medicine (Gold), Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, New York; Department of Pathology (Cho), University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey. To clarify the clinical profile of and diagnostic approach to AIDS, the clinical, neuroradiological (nervous system X-ray), and serological findings of 27 patients with cerebral toxoplasmosis and AIDS were reviewed; 19 were also analyzed neuropathologically. The clinical manifestations of this disorder varied, ranging from headache and fever to coma. The characteristic presentation included focal neurological symptoms and signs, usually of gradual onset. In addition, two-thirds of the patients exhibited more generalized cerebral dysfunction, with confusion and lethargy. Computed-tomographic (CT) scans revealed ring contrast enhancement, which was best correlated with the histological presence of blood vessel proliferation and inflammation surrounding the abscesses. In general, CT scans underrepresented the number of lesions eventually documented pathologically. Double-dose contrast administration and preliminary experience with magnetic resonance imaging suggest that these techniques may be superior to standard CT scanning in detecting toxoplasmal lesions. Prompt therapy resulted in rapid clinical improvement, documented by CT scan, associated with the development of an organizing tissue response in the host and elimination of parasites. Between September 1980 and February 1985, central nervous system (CNS) toxoplasmosis was diagnosed in 27 AIDS patients at Memorial and New York hospials in New York City. Antibody responses (immunoglobulin G) to Toxoplasma gondii were determined either by indirect immunofluorescent antibody tests or by the Sabin-Feldman dye test. After fixation in 10% buffered Formalin for 2 to 4 weeks, brain and spinal cord tissues from autopsied patients were serially sectioned into slices, and multiple sections from each patient were embedded in paraffin, stained, and examined by light microscopy. All 27 patients studied (diagnosed between September 1980 and February 1985) were male, ranging in age from 28 to 59 years. Twenty-five patients were homosexual (three were also intravenous drug users), one was a transfusion recipient, and one denied any risk factors but was suspected to be homosexual. CNS toxoplasmosis was the first manifestation of AIDS in six patients, and it developed in 3 weeks to 18 3D-Nav-4 months (mean, 6.8 months) after the diagnosis of AIDS; in one patient the AIDS diagnosis was made postmortem. Policy Keys: 1) Central Nervous System Disease Infection (IID), 2) Treatment: Symptom Management (IVB), 3) Clinical Manifestations: Opportunistic Infections (IIIA2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Ho, David D., MD; Rota, Teresa R., MA; Schooley, Robert T., MD; Kaplan, Joan C., PhD; Allan, J. Davis, MD; Groopman, Jerome E., MD; Resnick, Lionel, MD; Felsenstein, Donna, MD; Andrews, Charla A., MS; Hirsch, Martin S., MD. [solation of HTLV-II from Cerebrospinal Fluid and Neural Tissues of Patients with Neurologic Syndromes Related to the Acquired Immunodeficiency Syndrome. The New England Journal of Medicine, 12 December 1985, Vol. 313, No. 24: 1493-1497. Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston; Department of Medicine, New England Deaconess Hospital and Harvard Medical School, Boston, Massachusetts; Department of Dermatology, Mount Sinai Medical Center, Miami Beach, Florida. Fifty-six specimens from the nervous systems of 45 patients were studied to determine whether human T-cell lymphotropic virus type [II (HTLV-II) is directly involved in the pathogenesis of the neurologic disorders frequently seen in AIDS patients. HTLV-II was recovered from at least one specimen from 24 of 33 AIDS patients with neurologic symptoms, but none of 12 patients with unrelated neurologic deficits or no deficits had HTLV-II antibodies in cerebrospinal fluid or brain tissue. HTLV-II was also isolated from six of seven patients with AIDS or AIDS-related complex (ARC) and unexplained chronic meningitis. In addition, of 16 patients with AIDS-related dementia, 10 were positive for HTLV-III in the cerebrospinal fluid, brain tissue, or both. HTLV-III was also found in the spinal cord of a patient with myelopathy (disease of the spinal cord) and from the sural nerve (in the calf of the leg) of a patient with peripheral neuropathy. The authors conclude that HTLV-III is neurotropic (has an affinity for the nervous system), capable of causing acute meningitis and dementia, and may be the cause of the spinal cord degeneration and neuropathy seen in AIDS and ARC patients. Virus isolation studies were conducted on a total of 56 autopsy or biopsy specimens of brain, spinal cord, and peripheral nerve tissue obtained from the study sample. The presence of antibodies to HTLV-III in serum was assessed by fixed-cell indirect immunofluorescence and by Western blot techniques. Specimens were also cultured for other viruses to detect pathogenic central nervous system viruses, including herpes simplex virus, cytomegalovirus, and most enteroviruses (viruses of the digestive tract), myxoviruses (influenzalike viruses), and paramyxoviruses (larger myxoviruses, such as mumps virus). Descriptive findings are reported. Forty-five patients from Massachusetts General Hospital (Boston) and New England Deaconess Hospital (Boston) were included in this study, many of whom were selected because they had neurological diseases. The 45 patients included 29 with AIDS, 7 with ARC, and 9 previously 3D-Ho-5 Policy Keys: healthy men. When first evaluated, 41 patients were seropositive for antibodies to HTLV-III, 2 had seroconverted during acute meningitis, | remained seronegative, and 1 did not undergo serologic testing. 1) Central Nervous System Disease Infection (IID), 2) Virus isolation (VB2), 3) Other Characteristics of Disease: HTLV-II in Cerebrospinal Fluid and Brain Tissue (IIIF) Author(s): Title: Source: Institution: Findings: Method: Sample: Policy Keys: Resnick, Lionel, MD; DiMarzo-Veronese, Fulvia, PhD; Schupbach, Jorg, MD; Tourtellotte, Wallace W., MD, PhD; Ho, David D., MD; Muller, Franco, PhD; Shapshak, Paul, PhD; Vogt, Markus, MD; Groopman, Jerome E., MD; Markham, Phillip D., PhD; Gallo, Robert C., MD. Intra-Blood-Brain-Barrier Synthesis of HTLV-III-Specific IgG in Patients with Neurologic Symptoms Associated with AIDS or AIDS-Related Complex. The New England Journal of Medicine, 12 December 1985, Vol. 313, No. 24: 1498-1504. Laboratory of Tumor Cell Biology, National Institutes of Health, Bethesda, Maryland; Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland; Neurology Service, Veterans Administration Wadsworth Medical Center, Los Angeles, California; Infectious Disease Unit, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts; Department of Medicine and Institute for Medical Microbiology, University Hospital, Zurich, Switzerland; Departments of Medicine and Dermatology, Mount Sinai Hospital-Medical Center, Miami Beach, Florida. Intra-blood-brain barrier production of virus-specific antibody is good evidence of infection within the blood-brain barrier. Cerebrospinal fluid and sera from patients with neurologic symptoms of AIDS and AIDS- related complex (ARC) were tested for the presence of human T-cell lymphotropic virus type III (HTLV-II) antibodies. All patients were seropositive, and 22 of 23 (96%) had HTLV-III antibodies in their cerebro- spinal fluid. In eight of nine patients tested, the percentage of HTLV-III- specific immunoglobulin G (IgG) in the cerebrospinal fluid was higher than in serum, suggesting that HTLV-III infection of neurologic tissue occurs in the majority of patients with neurologic disease associated with AIDS. Serum and cerebrospinal fluid samples were collected from all patients. Fixed-cell indirect immunofluorescence assay, an enzyme-linked immunosorbent assay, a Western blot technique, and a radioimmunopre- cipitation technique were all used to detect antibodies to HTLV-II. IgG and albumin concentrations were quantified, and the intra-blood-brain barrier IgG synthesis rate was calculated. A total of 23 patients with AIDS or ARC were studied. The majority (21) of patients had neurologic disease. 1) Central Nervous System Disease Infection (IID) 3D-Res-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Koppel, Barbara S.; Wormser, Gary P.; Tuchman, Alan J.; Maayan, Shlomo; Hewlett, Dial, Jr.; Daras, Michael. Central Nervous System Involvement in Patients with Acquired Immune Deficiency Syndrome (AIDS). Acta Neurologica Scandinavica, 1985, Vol. 71: 337-353. Departments of Neurology and Internal Medicine (Infectious Diseases), Metropolitan Hospital, New York Medical College, Valhalla, New York. This study reports on an AIDS patient group with a preponderance of intravenous (I.V.) drug addicts. Of 121 AIDS patients studied at three New York hospitals, 28 (23%) had central nervous system (CNS) involve- ment. Of these 28, a neurologic symptom or disability was the primary reason for hospitalization for 16 (57%). In 10 of these 16, neurological symptoms were the first sign of AIDS; 6 had nonspecific weight loss and constitutional symptoms present for several weeks prior to hospitaliza- tion. For 6 of the 12 admitted for other reasons (primarily pulmonary or gastrointestinal infections), neurologic complaints included dizziness, blackouts, headache, and general weakness. Fifteen patients died during the study, from 6 days to | year after diagnosis. These patients exhibited three major syndromes: one was dominated by focal neurological features, usually due to toxoplasmosis; the second was characterized by headaches and meningeal signs which occurred primar- ily with cryptococcosis; and the third was characterized by progressive dementia. Overall, the most common cause of infection was Toxoplasma gondii; the most common presentation was headache with various degrees of focal dysfunction, including seizures. It is possible that a larger proportion of AIDS patients have subacute or chronic viral infection of the brain than are actually diagnosed: subtle manifestations may be missed without considerable knowledge of the patient's predisease personality and careful observation. Minimal changes in alertness, mood, personality, and reasoning are often attributed to fever, metabolic derangement, or reactive depression or dismissed without any inquiry. The authors emphasize that computerized tomographic (CT) scan and lumbar puncture are essential early diagnostic procedures. This clinical study evaluated patient medical records retrospectively, including CT scans, brain biopsies, serum immunoglobulin titers, tests on cerebral spinal fluid, and lumbar puncture. A retrospective review of medical records at three affiliated New York teaching hospitals between July 1981 and January 1984 identified 121 AIDS patients. Of these, 28 had CNS involvement (26 men, 2 women). All 28 patients except | (a man suspected of being homosexual) had risk factors for AIDS. The major AIDS risk factor was L.V. drug abuse (64%), but other CNS studies with AIDS risk groups of homosexuals and Haitians have produced similar findings. 1) Central Nervous System Disease Infection (IlID), 2) Diagnostic Indicators (IIIA3), 3) Populations: 1.V. Drug Abusers (IA2) 3D-Kop-7 Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Nielsen, Surl L., MD; Petito, Carol K., MD; Urmacher, Carlos D., MD; Posner, Jerome B., MD. Subacute Encephalitis in Acquired Immune Deficiency Syndrome: A Postmortem Study. American Journal of Clinical Pathology, December 1984, Vol. 82, No. 6: 678-682. Departments of Pathology and Neurology, Memorial Sloan-Kettering Cancer Center; New York Hospital-Cornell University Medical Center, New York, New York. Thirty-one out of 40 patients with AIDS examined at autopsy had significant central nervous system (CNS) disease. A subacute encephalitis (inflammation of the brain), found in 19 patients, was the most frequent condition. Toxoplasma encephalitis was found in five patients, primary lymphoma in three patients, and other conditions in the remaining four patients. Subacute encephalitis was characterized by marked brain atrophy and a progressive dementing illness. Cytomega- lovirus (CMV) was the infectious agent identified systemically most frequently in the subacute encephalitis cases (15 of 19 patients), followed by Pneumocystis carinii in 11 of the 19 patients, herpes simplex virus (HSV) in nine, Candida in eight, Mycobacterium avium-intracellulare in four, and Cryptosporidium in two. In all patients, more than one condition existed. However, no difference in the incidence of specific systemic disorders was found between the subacute encephalitis patients and other patients. In all cases, nearly every microscopic tissue section examined was abnormal, indicative of the diffuse nature of the infection process. Although the etiologic agent(s) of subacute encephalitis is unknown, the histopathology suggests an infection, and the most likely candidate is CMV. All cases were autopsied, with complete examination of the brain and spinal cord. At the time of autopsy, cerebrospinal fluid and/or fresh brain tissue were obtained for bacterial, fungal, and viral cultures. Brain and spinal cord were examined by standard techniques. Sections were examined by electron microscopy as well. CMV, HSV, and Toxoplasma were identified immunohistochemically. The 40 AIDS patients consisted of 39 men and | woman. Thirty-seven were homosexual, and three were intravenous drug users. The age range was 28 to 62 years (mean, 40). The patients had died at either Memorial Sloan-Kettering Cancer Center or New York Hospital-Cornell University Medical Center, New York City, between 1981 and 1983. 1) Central Nervous System Disease Infection (IIID), 2) Clinical Manifestations: Opportunistic Infections (I[IA2) 3D-Nie-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Moskowitz, Lee B., MD; Hensley, George T., MD; Chan, Joseph C., MD; Gregorios, Jocelyn, MD; Conley, Frances K., MD. The Neuropathology of Acquired Immune Deficiency Syndrome. Archives of Pathology and Laboratory Medicine, November 1984, Vol. 108, No. 11: 867-872. Departments of Pathology (Moskowitz, Hensley, Gregorios) and Medicine, Division of Infectious Diseases (Chan), University of Miami School of Medicine, Miami, Florida; Department of Surgery, Division of Neurosurgery, Stanford University, Palo Alto; Palo Alto Veterans Administration Hospital, Palo Alto, California (Conley). This report, prepared before human immunodeficiency virus encephalopathy was recognized, describes neuropathologic findings and histopathologic characteristics of various central nervous system (CNS) lesions that are found in association with AIDS. Histologically significant neuropathologic lesions were found in 38 of 52 autopsies, 29 of which were grossly visible lesions. The CNS lesions were believed to be the proximate cause of death in 15 of the 52 patients. Toxoplasma encephalitis was the most common disease involving the CNS and was often the primary or major manifestation of AIDS. Autopsy records of persons with AIDS were reviewed for the occurrence of pathologic lesions in the CNS. Sections from at least eight parts of the brain and three different levels of the spinal cord were routinely submitted for histologic examination, except for eight patients from outside the institution. Additional, premortem brain biopsy specimens from these patients were also examined. CNS tissue specimens from 52 patients who had died of AIDS were included. The mean age for 25 Haitian patients was 31 years (range, 22 to 67), and this group included 19 men and 6 women. The mean age of 19 homosexual men was 36 years (range, 20 to 54). The mean age of four intravenous drug abusers was 40 years (range, 26 to 54), and the group included three men and one woman. Finally, there was one hemophiliac patient aged 73 years. These cases were from the University of Miami/Jackson Memorial Medical Center, Miami Veterans' Administra- tion Hospital, Dade County (Florida) Medical Examiner's Office (Miami), and Cedars Medical Center (Miami). 1) Central Nervous System Disease Infection (IID) 3D-Mos-9 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Wong, Brian, MD; Gold, Jonathan W.M., MD; Brown, Arthur E., MD; Lange, Michael, MD; Fried, Richard, MD; Grieco, Michael, MD; Mildvan, Donna, MD; Giron, Jose, MD; Tapper, Michael L., MD; Lerner, Chester W., MD; Armstrong, Donald, MD. Central-Nervous-System Toxoplasmosis in Homosexual Men and Parenteral Drug Abusers. Annals of Internal Medicine, January 1984, Vol. 100, No. 1: 36-42. Infectious Disease Services, Departments of Medicine, Memorial Sloan- Kettering Cancer Center; St. Luke's-Roosevelt Medical Center; Beth Israel Hospital; Queens Hospital Medical Center; Lenox Hill Hospital, New York, New York. Central nervous system (CNS) toxoplasmosis developed in 7 of 269 patients with AIDS in New York City through July 1982. The common findings among these seven included focal neurologic abnormalities, mass lesions on computed-tomographic brain scans, lymphocytic cerebrospinal fluid pleocytosis (presence of more lymphatic white cells than normal in the fluid surrounding the brain and spinal column), and detectable immunoglobulin G (IgG) antibody to Toxoplasma gondii. However, high levels of IgG antibody, immunoglobulin M antibody to T. gondii, and positive open-brain biopsies were uncommon. Four of five patients improved with treatment, but two of the four relapsed. The authors sug- gest that an aggressive diagnostic and sometimes even therapeutic approach with sulfonamides and pyrimethamine is warranted when CNS toxoplasmosis is suspected in a patient with a positive blood test for human T-cell lymphotropic virus type III (HTLV-II) antibodies. Medical records, computed-tomographic brain scans, and histopathologic sections (specimens examined microscopically for disease) were reviewed, and serologic testing was performed to assess how often patients with AIDS and others at risk of developing the syndrome had evidence of past or latent CNS toxoplasmosis. Two hundred and sixty-nine New York and New Jersey patients with AIDS, including all patients reported to the New York City Health Department through 21 July 1982, were examined for this study. The subset of seven cases of CNS toxoplasmosis included six males (five of them known homosexuals), one of them an intravenous ([.V.) drug abuser, and one L.V. drug abusing female. The males ranged in age from 36 to 51 years (mean, 38), and the female was 51 years of age. 1) Central Nervous System Disease Infection (IID), 2) Treatment: Symptom Management (IVB) 3D-Won-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Snider, William D., MD; Simpson, David M., MD; Nielsen, Surl, MD; Gold, Jonathan W.M., MD; Metroka, Craig E., MD, PhD; Posner, Jerome B., MD. Neurological Complications of Acquired Immune Deficiency Syndrome: Analysis of 50 Patients. Annals of Neurology, October 1983, Vol. 14, No. 4: 403-418. Departments of Neurology (Snider, Simpson, Posner), Pathology (Simpson, Nielsen), and Medicine (Gold) (Infectious Disease Service), Memorial Sloan-Kettering Cancer Center; Departments of Neurology (Snider, Simpson, Posner), Pathology (Nielsen), and Medicine (Gold, Metroka), Cornell University Medical College, New York, New York. This study was conducted to identify neurological complications of AIDS and their causes. Four types of central nervous system complications were found: Toxoplasma gondii-caused abscesses in five patients, progressive multifocal leukoencephalopathy (degeneration of the white matter of the brain) in two patients, cryptococcal meningitis (inflammation of the membrane of the brain or spinal cord due to a fun- gus) in two patients, Candida albicans infection in one patient, and possible Mycobacterium avium-intracellulare infection in three patients. Eighteen patients suffered subacute encephalitis (inflammation of the brain), possibly attributable to cytomegalovirus infection. Tumors found included primary lymphoma of the brain in three patients and meningeal invasion by systemic lymphoma in four patients. Vascular complications included nonbacterial thrombotic endocarditis (inflam- mation of the lining of the heart resulting in blood clots) in two patients and cerebral hemorrhages associated with an abnormally small number of platelets in the circulating blood in three patients. Undiagnosed central nervous system problems included focal brain lesions in three patients and self-limiting aseptic meningitis (inflammation of meninges not due to a living organism) in four patients. Eight patients had disease of the peripheral (not central) nervous system. Full postmortem examinations were performed on 20 deceased AIDS patients, 16 of these resulting in a specific neuropathological diagnosis. For 12 other patients, diagnoses of cause were based on biopsy material, cultures, or cellular or blood test findings. For another 22 patients neurological abnormalities were present, but no specific cause of death could be established. Fifty of 160 AIDS patients evaluated from January 1980 through January 1983 at Memorial Sloan-Kettering Cancer Center and New York Hospital, New York City, developed neurological complications and were included in this study. This group included 41 homosexual or bisexual males, 6 intravenous (I.V.) drug abusers (2 female), and 2 Haitian and 1 Colombian male who denied both homosexuality and [.V. drug abuse; their ages ranged from 23 to 56 years (mean, 36.5; median, 37). 1) Central Nervous System Disease Infection (IID) 3D-Sni-11 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Whelan, Margaret Anne, MD; Kricheff, Irvin I., MD; Handler, Michael, MD; Ho, Victor, MD; Crystal, Kenneth, MD; Gopinathan, Govindan, MD; Laubenstein, Linda, MD. Acquired Immunodeficiency Syndrome: Cerebral Computed Tomographic Manifestations. Radiology, 1983, Vol. 149: 477-434. Departments of Radiology (Whelan, Kricheff, Crystal) Neurology (Gopinathan), Neurosurgery (Handler), and Medicine (Laubenstein), New York University Medical Center, New York. The hospital records of 19 male patients with documented central nervous system involvement associated with AIDS were reviewed. For the computed tomography (CT) findings, the primary emphasis was on determining the number and location of cerebral lesions. Neurologic findings were characterized by encephalopathy in 13 patients and abnormality in only one area in 6 patients. Ten patients demonstrated one or more structural lesions on CT, while in 9 cases the CT scans were either normal or showed nonspecific atrophy (wasting and shrinkage) and mild ventricular (brain section) enlargement. Of the 10 patients with structural lesions on CT, 7 had toxoplasmosis, | had lymph- oma, and | had a nonspecific encephalitis (brain inflammation). In the seven cases with toxoplasmosis, five had multiple CT lesions in various areas of the brain, specifically the basal ganglia, grey matter-white matter interface, or the white matter itself. All but one patient showed initial improvement after therapy with pyrimethamine and sulfadiazine. In a later series of 13 patients with AIDS, toxoplasmosis was the presenting infection in one case. All 13 patients showed decreased intellectual function with seizures and/or focal neurological deficits. In seven patients the diagnosis was made solely on the basis of a CT scan. Due to the frequency of toxoplasmosis in AIDS patients, this hospital now places patients on trials of pyrimethamine and sulfadiazine, with clinical improvement generally apparent in | week and CT improvement in 2 weeks. Cerebral CT scans were done of 19 AIDS patients, and their medical records were reviewed. Clinical, laboratory, and radiologic findings were analyzed. A group of 19 male AIDS patients with documented central nervous system involvement were studied. Their ages ranged from 26 to 56 years, and only three of them over the age of 40. Eighteen were homosexual, and five were intravenous drug abusers. Fourteen patients had a history of Kaposi's sarcoma or opportunistic infections of the lungs, stomach, or bowel. 1) Central Nervous System Disease Infection (IID), 2) Treatment: Symptom Management (IVB) 3D-Whe-12 [II. Characteristics of Disease E. Immunological Aspects Author(s): Title: Source: Institution: Findings: Method: Sample Size: Rodman, Toby C.; Laurence, Jeffrey; Pruslin, Fred H.; Chiorazzi, Nicholas; Winston, Ronald. Naturally Occurring Antibodies Reactive with Sperm Proteins: Apparent Deficiency in AIDS Sera. Science, 7 June 1985, Vol. 228: 1211-1215. Department of Cell Biology and Anatomy, Cornell University Medical College (Rodman); Department of Medicine, New York Hospital-Cornell Medical Center (Laurence); Department of Cell Biology (Pruslin), and Department of Immunology (Chiorazzi), Rockefeller University; Harry Winston Research Foundation (Winston), New York, New York. This study identified a set of naturally occurring immunoglobulin M (IgM) antibodies in the acrosomal cap region of human sperm that are immuno- logically reactive with the component(s) of human sperm capable of inhibiting lectin-induced lymphocyte proliferation. These [gM antibodies appear to be normal components of circulating immunoglobulins and are not elicited by sperm. These antibodies were present in more than 99% of healthy male and female subjects (aged | day to 40 years). An absence or marked deficiency of these antibodies was evident in 40% of AIDS patients, 33% of AIDS-related complex (ARC) patients, and 21% of asymptomatic homosexual males at risk for AIDS. Their distribution in the general population suggests that these antibodies are normal components of human sperm and may be components (possibly regulatory) of the immune system. During anal intercourse, sperm are introduced into an environment where the potential for inducing specific resistance may be maximized. Results suggest that certain IgM antibodies may have a role in maintaining immunologic balance, and an overload of proteins reactive to a specific set of IgM antibodies may disrupt the equilibrium, depleting a critical set of [gM antibodies and creating a medium in which the AIDS-associated retrovirus can establish itself. Another theory suggested by the results is that an overload of sperm proteins could suppress proliferation of a specific fraction of T cells, leading to an immunodeficiency state. In this laboratory study, blood sera were examined for reactivity with the acrosomal cap region of human sperm smears by indirect immunofluor- escence, confirmed by immunoblots. The study group consisted of homosexual males (45 ARC patients and 20 AIDS patients); a high-risk group of intravenous drug users, hemophiliacs, and maternal-AIDS infants (eight asymptomatic subjects, one asympto- matic female prostitute, three ARC patients, one female-prostitute AIDS patient); and a control group of unknown sexual preference (45 3E-Rod-1 healthy males, 35 adult females; 21 adults and 30 children aged | to 2 years hospitalized for non-immune system diseases). Policy Keys: 1) Immunological Aspects: Anti-sperm Antibodies (IIE), 2) Transmission: Sexual Activity (IIA), 3) Cofactors: Immunocompromised Host (IC3) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Siegel, Jay P.; Djeu, Julie Y.; Stocks, Naomi I.; Masur, Henry; Gelmann, Edward P.; Quinnan, Gerald V., Jr. Sera from Patients with the Acquired Immunodeficiency Syndrome Inhibit Production of Interleukin-2 by Normal Lymphocytes. The Journal of Clinical Investigation, June 1985, Vol. 75: 1957-1964. Division of Virology, Office of Biologics Research and Review, Center for Drugs and Biologics, Food and Drug Administration; Critical Care Medicine Department, Clinical Center, and Medicine Branch, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. To better understand the mechanism of immunodeficiency, the authors studied the effects of blood sera from AIDS patients on interleukin 2 (IL- 2); IL-2 plays a central role in the development of many immune responses. Compared with sera from healthy controls, sera from AIDS patients were found to suppress phytohemagglutinin (PHA; a plant product that agglutinates red blood cells)-induced IL-2 by normal blood mononuclear cells. However, sera from homosexual contacts of AIDS patients and from adults with acute cytomegalovirus (CMV) infection were not found to have this suppressive activity. The suppressive effect of the AIDS sera could not be attributed to absence of a stimulatory or nutritive factor, to inactivation of I[L-2, to inhibition of the IL-2 measurement test, or to increased turnover of IL-2. The sera acted directly on the groups of cells that produce IL-2 at an early stage, and this action was not mediated by any other known process or immune system component. The suppressive activity was stable under both acid (pH 3) and alkaline (pH 10) conditions and at 60°C; it was inactivated at 100°C and was not soluble in ether. The authors report that because IL-2 plays a central role in the development of many immune responses, the serum factor(s) that inhibits [IL-2 production could contribute significantly to the immunodeficiency of AIDS. Mononuclear cells were isolated from healthy donor blood. IL-2 production was induced by cultivating mononuclear cells in the presence of purified PHA. IL-2 was measured by its ability to support proliferation of the IL-2-dependent murine lymphocyte cell line CTLL- 2. Sera were tested for direct and cell-mediated lymphocyte toxicity. Immunoglobulin G and immunoglobulin M levels were measured by single radial immunodiffusion assay, and serum cortisol levels were measured by radioimmunoassay. Blood samples were obtained from a total of 17 AIDS patients, six adult controls, seven healthy homosexual contacts of AIDS patients, and five adult males before and during CMV infections (two of whom developed fever and an enlarged spleen). (Not all subjects’ sera were used in all the experiments.) All subjects with AIDS and their contacts were being followed at the Clinical Center, National Institutes of Health, Bethesda, Maryland. 3E-Sie-2 Policy Keys: 1) Immunological Aspects (IIE), 2) Treatment: Therapeutic Intervention (IVC), 3) Blood Product Safety: Viral Inactivation (VB3) Author(s): Titles Source: Institution: Findings: Method: Sample Size: Policy Keys: Dorsett, Brent, BS; Cronin, William, MS; Chuma, Vera, BS; loachim, Harry L., MD. Anti-Lymphocyte Antibodies in Patients with the Acquired Immune Deficiency Syndrome. The American Journal of Medicine, April 1985, Vol. 78: 621-626. Department of Pathology, Lenox Hill Hospital and College of Physicians and Surgeons of Columbia University, New York, New York. This study was undertaken to investigate the mechanisms by which human T-cell lymphotropic virus type III (HTLV-III) infection leads to the complex immune deregulations of AIDS. When lymphocytes from a normal donor were incubated with blood serum samples from patients with AIDS or AIDS-related complex (ARC), substantial increases (up to 75%) in the number of surface immunoglobulin-positive lymphocytes resulted. In contrast, these increases did not occur in samples incubated with blood serum from patients with non-AIDS-related diseases or from normal control subjects. The additional surface immunoglobulin-positive lymphocytes were identified as binding predominantly with helper T cells, which explained the decrease in the helper/suppressor T-cell ratios. AIDS serum samples consistently generated significant increases in surface immunoglobulin-positive lymphocytes compared with control samples. The number of surface immunoglobulin-positive lymphocytes in some patients showed changes that paralleled the progress of disease; two patients with high levels developed opportunistic AIDS infections 4 to 6 months later. In this study, blood from a normal blood donor was incubated with blood samples from patients with AIDS, ARC, or non-AIDS-related diseases and normal control subjects. The percentage of surface immunoglobulin- positive lymphocytes was determined by counting 100 cells. Lympho- cytes were radioactively labeled and then counted under ultraviolet illumination to determine whether AIDS serum antibodies reacted preferentially to helper or suppressor T cells. Total T cells and helper/suppressor T-cell ratios were determined by standard methods with OKTI1, OKT4%, and OKT8 monoclonal antibodies. Serum samples were collected from 31 male patients with AIDS, 18 male patients with lymph node disease and fever of unexplained cause (ARC), 18 male patients with diseases unrelated to AIDS, and 30 healthy male control subjects. 1) Immunological Aspects (IIE), 2) Incubation Period and Disease Stages (11C) 3E-Dor-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lewis, Dorothy E.; Puck, Jennifer M.; Babcock, George F.; Rich, Robert R. Disproportionate Expansion of a Minor T Cell Subset in Patients with Lymphadenopathy Syndrome and Acquired Immunodeficiency Syndrome. The Journal of Infectious Diseases, March 1985, Vol. 151, No. 3: 555-559. Howard Hughes Medical Institute; Department of Microbiology and Immunology, Baylor College of Medicine; Department of Surgery, M.D. Anderson Hospital and Tumor Institute, Houston, Texas. Patients with AIDS and AIDS-related complex (ARC) were examined to determine whether the profound immunosuppression seen in these patients may be associated with more specific alterations in suppressor T-cell subpopulations. AIDS and ARC patients were found to differ significantly from normal subjects and from individuals suffering from acute viral infections. These differences included an increase in subpopulations of suppressor (T8+) T cells bearing an additional cell surface determinant, Leu/, and an increase in numbers of Leul + cells in virally infected patients, but an absolute decrease in cell lines in all patients with AIDS. This finding was in marked contrast to the relative infrequency of T8+Leu7 cells in normal subjects. The data suggest that as the immunodeficient state progresses and the number of white blood cells decreases, eventually only T8+Leu/ cells remain. Blood specimens were collected from the subjects and analyzed for various lymphocyte subpopulations. Blood cells were examined by direct or indirect immunofluorescence with OKT3, OKT4, OKT8, OKTI11l, and OKMI1 monoclonal antibodies. Twenty patients with AIDS were studied, divided into two subgroups by the percentage of detectable T cells, although there were no apparent clinical differences between the two subgroups. Another 20 homosexual men were classified as having ARC on the basis of a 3-month history of lymph node disease, weight loss, or fever. Eleven patients with acute viral diseases (CMV, Epstein-Barr virus, or herpes simplex virus) were also included, as well as 10 normal control subjects. 1) Immunologic Aspects (IIIE), 2) Disease Stages (IIIC) 3E-Lew-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Winter, Stephen M.; Bernard, Edward M.; Gold, Jonathan W.M.; Armstrong, Donald. Humoral Response to Disseminated Infection by Mycobacterium avium- Mycobacterium intracellulare in Acquired Immunodeficiency Syndrome and Hairy Cell Leukemia. The Journal of Infectious Diseases, March 1985, Vol. 151, No. 3: 523-527. Department of Internal Medicine, New York Hospital-Cornell University Medical Center; Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York. This study compared the humoral responses of AIDS patients and hairy cell leukemia patients to disseminated Mycobacterium avium- intracellulare infection. Both types of patients appear to be particularly susceptible to widespread systemic infection with this organism. In this study all 10 AIDS patients with M. avium-intracellulare infections did not produce antibody to the infection and showed antimycobacterial levels very similar to those of uninfected AIDS patients and controls (low or undetectable). All three infected hairy cell leukemia patients had significantly higher antimycobacterial levels than uninfected hairy cell leukemia patients or controls. One infected hairy cell leukemia patient, studied serially, showed a more than 100-fold increase in antibody level with the onset of infection. These results further demonstrate that AIDS involves a functional defect in humoral as well as cell-mediated immunity. Results also indicate that detection of antibody is not clinically useful in diagnosing M. avium- intracellulare infection in AIDS patients, but it may provide early detection in hairy cell leukemia patients or other immunodeficient patients who can produce specific antibody. Detection of specific microbial antigens or metabolites in blood or other body fluids seems to be a better method for AIDS patients. Humoral responses of patients and controls were compared. This study used three antibody assays: immunodiffusion, indirect immunofluor- escence, and enzyme-linked immunosorbent assay (ELISA). Immunodiffu- sion and indirect immunofluorescence were far less sensitive than ELISA (only sera with ELISA values of >1:512 were clearly positive by the other two assays) and were not used for specific determination of antibody levels. Serum was stored at -20°C before testing. Serial antibody levels in laboratory animals immunized with mycobacterial antigens were also measured. Thirty AIDS patients (10 infected with M. avium-intracellulare, 20 not infected) and 10 hairy cell leukemia patients (3 infected, 7 not infected) were studied. Controls consisted of 15 hospitalized patients without evidence of mycobacterial infection and 18 healthy lab workers. 1) Immunological Aspects: Humoral Immunity Defect (IIIE), 2) Other Clinical Manifestations: Mycobacterium avium-intracellulare (IIIA4) 3E-Win-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Chan, Wing C., MB, BS; Brynes, Russell K., MD; Spira, Thomas J., MD; Banks, Peter M., MD; Thurmond, Cathy C., MT (ASCP); Ewing, Edwin P., Jr., MD; Chandler, Francis W., DVM, PhD. Lymphocyte Subsets of Lymph Nodes of Homosexual Men with Generalized Unexplained Lymphadenopathy: Correlation with Morphology and Blood Changes. Archives of Pathology and Laboratory Medicine, February 1985, Vol. 109: 133-137. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia (Chan, Brynes, Thurmond); Department of Pathology, Mayo Clinic, Rochester, Minnesota (Banks); Division of Host Factors, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Spira, Ewing, Chandler). This study examined the proportion and distribution of major subsets of T-cells in lymph nodes from 20 homosexual men with lymphadenopathy syndrome to determine whether T-cell subsets in the lymph nodes (1) differed significantly from those of patients not at risk for AIDS, (2) correlated with the absolute lymphocyte count and changes observed in T-lymphocyte subsets in the peripheral blood, and (3) had any prognostic significance. Frozen sections of lymph nodes were studied. In T-cell areas of the lymph nodes, the mean helper/suppressor T-cell ratio was significantly lower in the homosexual group (1.07) than in the control group (2.49). The lymph node helper/suppressor T-cell ratios of the homosexual patients showed less variation than those of the control group. According to the authors, whether the lymph node helper/suppressor T- cell ratio has prognostic significance in patients with lymphadenopathy warrants further investigation. Frozen sections of lymph nodes were studied with monoclonal antibodies to T-cell subsets and the HLA-DR antigen. In seven homosexual men, cell suspensions from the same lymph nodes were analyzed with a flourescence-activated cell sorter; results obtained by immunohisto- chemistry were comparable. Study subjects included 20 homosexual men with lymphadenopathy and a control group of 14 patients with follicular hyperplasia but not at special risk of developing AIDS. 1) Immunological Aspects (IIE), 2) Precursors of AIDS: Lymphadeno- pathy (IIIB) 3E-Cha-6 Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Jothy, Serge, MD, PhD, FRCPC; Gilmore, Norbert, PhD, MD; El'Gabalawy, Hani, MD; Prchal, Jaroslav, MD, FRCPC. Decreased Population of Leu-7+ Natural Killer Cells in Lymph Nodes of Homosexual Men with AIDS-Related Persistent Lymphadenopathy. Canadian Medical Association Journal, 15 January 1985, Vol. 132: 141- 144, Department of Pathology and Divisions of Clinical Immunology and Hematology, Department of Medicine, Royal Victoria Hospital and McGill University, Montreal, Canada. This study was undertaken to determine whether the number of natural killer cells is diminished in persistent lymphadenopathy syndrome (PLS). In the lymph nodes of patients with an AIDS-related complex, the helper/suppressor T-cell ratio was significantly lower than in normal lymph nodes, even though the proportion of total T lymphocytes was not significantly different. Lymph nodes from these patients also contained 91% and 81% fewer natural killer cells than normal lymph nodes and lymph nodes from patients with non-AlDS-related hyperplastic lymphadenopathy, respectively. Lymph nodes were obtained by surgical biopsy from patients with AIDS- related complex and control subjects. T-cell subpopulations were quantitated by direct fluorescence microscopy with OKT3, OKT#%, and OKT8 monoclonal antibodies. There were seven homosexual men with AIDS-related complex. Control subjects were eight heterosexual, non-Haitian men with reactive hyperplasia and six men whose normal lymph nodes had been biopsied because malignancy was suspected. 1) Immunological Aspects (IIE) 3E-Jot-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kekow, J.; Kern, P.; Dietrich, M.; Gross, W.L. T- und B-Zellreaktionen bei AIDS und AIDS-Risikogruppen (T- and B-Cell Reactivity in AIDS and High Risk Groups for AIDS). Immunitat und Infektion, 1985, Vol. 13, No. 1: 26-28. Medizinische Universitatsklinik Kiel (Kekow, Gross); Bernhard-Nocht- Institut fur Schiffs- und Tropenkrankheiten (Kern, Dietrich), Hamburg, Federal Republic of Germany. T-cell changes have long been associated with AIDS. At present, there is discussion about an additional B-cell dysfunction. Starting with the generally accepted T-cell dysfunction, tests were conducted for B-cell response in vitro to T-cell-independent mitogens or polyclonal B-cell activators. The results show a functional disruption of the B-cell system in AIDS, which could be interpreted within the framework of polyclonal B-cell activation in vivo. Opposed to this hypothesis are the nearly normal values for immunoglobulin M that were found. Other mechanisms of B- cell dysfunction are also suggested by the B-cell changes that can already be found in AIDS high-risk groups, for example, a direct cytopathogenic effect of the recently discovered AIDS virus, human T- cell lymphotropic virus type III. Further longitudinal studies are necessary among high-risk AIDS groups in view of the complex immune regulation disruptions. Homosexual men were examined for immunologic findings and divided into four groups for analysis: patients with AIDS, patients with AIDS- related complex (ARC), patients with persistent lymphadenopathy, and patients without substantial clinical symptoms. Heterosexual men were used as controls. Fifteen German subjects, including three apparently healthy homosexual men, six homosexual men with persistent lymphadenopathy, three patients with ARC, and three patients with AIDS, were studied and compared with six heterosexual controls. 1) Immunological Aspects (IIIE), 2) Populations: Homosexuals (IA1), 3) Geographic Trends: Europe (West Germany) (IB4) 3E-Kek-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Fahey, John L., MD; Prince, Harry, PhD; Weaver, Michael, PhD; Groopman, Jerome, MD; Visscher, Barbara, MD, DPh; Schwartz, Kendra, MPh; Detels, Roger, MD. Quantitative Changes in T Helper or T Suppressor/Cytotoxic Lymphocyte Subsets That Distinguish Acquired Immune Deficiency Syndrome from Other Immune Subset Disorders. The American Journal of Medicine, January 1984, Vol. 76: 95-100. Medical Immunology Laboratory, Department of Microbiology and Immunology and Division of Hematology/Oncology, Department of Medicine, University of California School of Medicine; Department of Epidemiology, University of California School of Public Health, Los Angeles, California. This study compared the T-cell subgroups found in the blood of various study groups. A decrease in the number of helper T cells was found to be characteristic of AIDS with Kaposi's sarcoma or opportunistic infection. An increased number of suppressor T cells may occur in various conditions -- cytomegalovirus and other viral infections -- in healthy, homosexually active males and in otherwise healthy hemophiliacs receiv- ing factor VIII. Lowered helper/suppressor T-cell ratio, which can result from either fewer helper cells or more suppressor cells, does not by itself distinguish between AIDS and other conditions. AIDS is characterized by both a reduced helper/suppressor T-cell ratio and a decreased number of helper T cells. The two T-cell subpopulations can change independent- ly. A decrease in the number of helper T cells occurring independently of other lymphoid subpopulations (e.g., suppressor T cells, B cells) and the close association of the decrease in the number of helper T cells with AIDS are findings consistent with a distinct pathogensis for AIDS. In this baseline study, the health status of healthy homosexual males and controls was determined from a self-administered questionnaire. Blood samples from all subjects were tested for immune parameters at the same laboratory: white blood cell counts with differential were determined in fresh blood specimens and T-cell subpopulations were quantitated by immunofluorescence with Leul, Leu2, and Leu3 monoclonal antibodies. California study groups included 32 patients with AIDS/Kaposi's sarcoma, 27 patients with AIDS/opportunistic infection, 48 male homosexuals with lymphadenopathy syndrome, 89 healthy homosexual males recruited from gay students and their associates, and 49 healthy adult controls (65% female; age 20 to 58 years; median, 38 years) recruited from hospital personnel. Patients were seen at UCLA medical clinics. 1) Immunological Aspects (IIE) 3E-Fah-9 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Ciobanu, Niculae; Welte, Karl; Kruger, Gerard; Venuta, Salvatore; Gold, Jonathan; Feldman, Stuart P.; Wang, Chang Yi; Koziner, Benjamin; Moore, Malcolm A.S.; Safai, Bijan; Mertelsmann, Roland. Defective T-Cell Response to PHA and Mitogenic Monoclonal Antibodies in Male Homosexuals with Acquired Immunodeficiency Syndrome and Its in Vitro Correction by Interleukin-2. Journal of Clinical Immunology, 1983, Vol. 3, No. 4: 332-340. Memorial Sloan-Kettering Cancer Center, New York, New York. This study evaluated the response of lymphocytes from 21 homosexual patients (12 with Kaposi's sarcoma, 5 with opportunistic infections, and 4 with reactive lymphadenopathy) to mitogenic stimulation in vitro. For patients with opportunistic infection or Kaposi's saroma, the response of lymphocytes to stimulation was markedly reduced regardless of the stimulus used. For patients with lymphadenopathy alone, lymphocytes responded to only one of the types of stimulation (OKT3 antibody). The production of an important cellular messenger, interleukin 2 (IL-2), was also markedly lower in response to stimulation for patients with opportunistic infection and Kaposi's sarcoma than for normal controls. Addition of IL-2 partly restored the activity of the lymphocytes in response to mitogenic stimulation in vitro. Blood samples from homosexual males with Kaposi's sarcoma, opportunistic infections, or lymphadenopathy were evaluated during the summer of 1982 at Memorial Sloan-Kettering Cancer Center in New York City. Blood samples from 21 homosexual males were studied. 1) Immunological Aspects (IIE) 3E-Cio-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Schroff, Robert W.; Gottlieb, Michael S.; Prince, Harry E.; Chai, Loretta L.; Fahey, John L. Immunological Studies of Homosexual Men with Immunodeficiency and Kaposi's Sarcoma. Clinical Immunology and Immunopathology, 1983, Vol. 27, No. 3: 300-314. Department of Microbiology and Immunology (Medical Immunology Laboratory) and Department of Medicine (Division of Clinical Immunology/Allergy), University of California School of Medicine, Los Angeles, California. This study examines cellular and humoral immune function in patients with AIDS in order to analyze the disturbed immune response in these patients and better delineate the pathogenesis of the immune defects and identify interrelationships among three clinical presentations: multiple opportunistic infections, generalized prolonged lymphadenopathy, and Kaposi's sarcoma (KS). All 46 subjects had a common immune abnormality consisting of a reduction in the helper T-cell subpopulation. The suppressor T-cell subpopulation was numerically normal in all three conditions. The net effect of these phenomena was to decrease the helper/suppressor T-cell ratio in AIDS patients in all three groups. The immune deficiency in these patients was most evident in the T-cell component of the immune system. Percentages of B cells, circulating immunoglobulin levels, and natural killer cell and antibody-dependent cell-mediated cytotoxic functions were normal. Proliferative responses to antigen and mitogen were typically decreased in patients with AIDS and KS, but not in those with the prolonged lymphadenopathy syndrome or in a control group of healthy homosexuals. Peripheral blood was collected and examined by using an indirect immunofluorescence assay, analysis of serum immunoglobulin levels, and other tests for immunologic function. Study findings were presented as case-control comparisons. Study subjects included 46 Los Angeles patients with AIDS who received clinical and laboratory evaluation at the University of California-Los Angeles Center for the Health Sciences: 24 male patients with multiple opportunistic infections (aged 22 to 51 years; mean, 34), 12 with general- ized prolonged lymphadenopathy (aged 23 to 47; mean, 35), and 10 with Kaposi's sarcoma (aged 33 to 46 years; mean, 37). Two control populations were used: a group of 24 healthy homosexual men from the private practice of a Los Angeles area physician, and a healthy control group of random male volunteers. 1) Immunological Aspects (IIIE) 3E-Sch-11 [II. Characteristics of Disease F. Other RE Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Archibald, D.W.; Zon, L.; Groopman, J.E.; McLane, M.F.; Essex, M. Antibodies to Human T-Lymphotropic Virus Type [II (HTLV-II) in Saliva of Acquired Immunodeficiency Syndrome (AIDS) Patients and in Persons at Risk for AIDS. Blood, March 1986, Vol. 67, No. 3: 831-834. Department of Cancer Biology, Harvard School of Public Health, Boston; Hematology/Oncology Division, Harvard Medical School, Boston; New England Deaconess Hospital, Boston, Massachusetts. Whole saliva samples collected from available Bostonians at risk for infection with human T-cell lymphotropic virus type III (HTLV-II) from late 1984 through early 1985 were analyzed for the presence of antibodies to viral proteins. Those who had antibodies to the virus- encoded glycoproteins gpl60 and gpl20 in their saliva included 14 of 20 (70%) AIDS patients, 14 of 15 (93%) AIDS-related complex (ARC) patients, 9 of 20 (45%) sex partners of AIDS or ARC patients, 4 of 18 (22%) healthy homosexual males, none of 10 patients hospitalized for cancer therapy, and none of 11 laboratory workers exposured to HTL V-III products. The blood sera of all the AIDS and ARC patients had antibodies to these proteins as well. Serum and salivary antibody status were the same among sexual partners of AIDS and ARC patients and healthy homosexuals. Since salivary immunoglobulin A antibodies were detectable in all the subjects (27 of 27) that were positive for serum antibodies except the AIDS patients, a screening test for the detection of virus-infected healthy carriers might be conducted by using saliva rather than blood. Collected and frozen saliva samples were tested by radioimmunoprecipi- tation. Serum from an AIDS patient known to be positive for the various HTLV-III antigens was used as a positive control. Blood serum samples from the same patients were obtained at approximately the same time and also tested by immunoprecipitation. Samples were collected in Boston during late 1984 and early 1985 from 20 AIDS patients, 15 ARC patients, 20 sexual partners of AIDS or ARC patients, 18 healthy homosexuals, 10 patients hospitalized for cancer therapy, and 11 laboratory workers exposed to HTLV-II products (these last two groups served as controls). 1) Other Characteristics of Disease: HTLV-II in Saliva (IlIF), 2) Transmission: Saliva (IIG) 3F-Arc-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Fujikawa, Leslie S.; Palestine, Alan G.; Nussenblatt, Robert B.; Salahuddin, S. Zaki; Masur, Henry; Gallo, Robert C. Isolation of Human T-Lymphotropic Virus Type III from the Tears of a Patient with the Acquired Immunodeficiency Syndrome. The Lancet, 7 September 1985, Vol. 2, No. 8454: 529-530. Clinical Branch, National Eye Institute; Laboratory of Tumor Cell Biology, National Cancer Institute; Critical Care Medicine Department, Clinical Center; National Institutes of Health, Bethesda, Maryland. Human T-cell lymphotropic virus type III (HTLV-II) was isolated from the tears of one of 7 patients with AIDS or AIDS-related complex (ARC). The tears from 5 healthy individuals did not show HTLV-II. The recovery of HTLV-III from tears suggests that they may harbor free virus or may contain virus-positive cells, and it is consistent with HTLV-II recovery from other body fluids. The authors suggest that although casual contact with tears has not been shown to cause AIDS, direct contact with the tears of these patients should be minimized, including contact during routine eye examinations. The presence of infectious HTLV-II was determined by transmission and retransmission of virus to mitogen-stimulated normal peripheral blood mononuclear cells. HTLV-II production by tear-infected white blood cells was monitored by assays for reverse transcriptase (an enzyme marker for the virus) and by indirect fixed-cell immunofluorescence tests. Tear samples from the eyes of 12 individuals were examined. Six samples were from AIDS patients, one sample was from a patient with ARC, and five samples were taken from healthy control subjects (National Institutes of Health employees aged 29 to 40 years) with no known risk factors for the development of AIDS. 1) Other Characteristics of Disease: HTLV-III in Tears (IIIF), 2) Infection Control in Occupational Settings (VC) 3F-Fuj-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lecatsas, G.; Houff, F.; Macher, A.; Gelman, E.; Steis, R.; Reichert, C.; Masur, H.; Sever, J.L. Retrovirus-like Particles in Salivary Glands, Prostate and Testes of AIDS Patients. Proceedings of the Society for Experimental Biology and Medicine, 1985, Vol. 178: 653-655. Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, Laboratory of Pathology, Division of Cancer Treatment, National Cancer Institute, Critical Care Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland. Retrovirus particles were identified in the salivary and prostate glands of two AIDS patients, as well as in their testicles. The retrovirus was apparently human T-cell lymphotropic virus type III (HTLV-II). Both patients were homosexual men with histories of opportunistic infections, Pneumocystis carinii pneumonia, and cytomegalovirus infection. Both patients died, and HTLV-III was found in their tissues at autopsy. The authors suggest that the presence of viral particles in the salivary gland, prostate gland, or testicle of these two AIDS patients indicates that saliva and semen may be vehicles for transmission of the AIDS virus. Case reports of two AIDS patients and electron microscopic findings for their autopsied tissues were evaluated. Two homosexual men (one white, one black) who died of AIDS were studied. 1) Other Characteristics of Disease: HTLV-III in Saliva and Semen (I1IF) 3F-Lec-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Groopman, Jerome E.; Salahuddin, S. Zaki; Sarngadharan, M.G.; Markham, Phillip D.; Gonda, Matthew; Sliski, Ann; Gallo, Robert C. HTLV-II in Saliva of People with AIDS-Related Complex and Healthy Homosexual Men at Risk for AIDS. Science, 26 October 1984, Vol. 226, No. 4673: 447-9. Hematology-Oncology Division, Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts (Groopman); Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Salahuddin, Sliski, Gallo); Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland (Sarngadharan, Markham); Program Resources Inc., Frederick Cancer Research Facility- National Cancer Institute, Frederick, Maryland (Gonda). Blood and saliva tests for human T-cell lymphotropic virus type III (HTLV-II) antibody in 20 individuals (including AIDS and AIDS-related complex [ARC] patients and healthy homosexuals) showed that all of the study population except two healthy homosexuals had blood tests that were positive for HTLV-III antibody, evidence that the 18 had been exposed to the AIDS virus. HTLV-III itself was found in the blood of one AIDS patient, four ARC patients, and two healthy homosexual males. HTLV-II was also isolated from saliva samples from four ARC patients and four healthy homosexuals. This indicates that the possibility of HTLV-II transmission by saliva should be considered even though there is no evidence to date of AIDS transmission by casual contact. Samples of serum, blood, and saliva were tested for HTLV-III antibody by both enzyme-linked immunosorbent assay and Western electroblot technique. ~~ HTLV-III itself was monitored by assays for reverse transcriptase, electron mIiCroscopy, immunofluorescence, and radioimmunoassays with HTL V-III-specific antisera. A total of 20 individuals were tested, including 4 AIDS patients, 10 persons with ARC, and 6 healthy homosexual men at risk for AIDS. 1) Other Characteristics of Disease: HTLV-II in Saliva (IIIF) 3F-Gro-4 IV. Treatments for AIDS A. General Support Care Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Dilley, James W., MD; Ochitill, Herbert N., MD; Perl, Mark, MBBS; Volberding, Paul A., MD. Findings in Psychiatric Consultations with Patients with Acquired Immune Deficiency Syndrome. American Journal of Psychiatry, January 1985, Vol. 142, No. 1: 82-86. San Francisco General Hospital and University of California, San Francisco, California. In an effort to identify recurrent psychiatric issues specific to AIDS patients, this article presents a set of psychiatric profiles. Thirteen of 40 patients with AIDS admitted to the wards of a large San Francisco hospital were seen by the staff of a psychiatric consultation service. Depression was the stated reason for referral for 10 of these patients: of these, 2 had major depression, | had dysthymic disorder, and 7 had adjustment disorder with depressed mood. Recurrent psychological themes of the 13 patients were dealing with a life-threatening illness, uncertainty about the implications of an AIDS diagnosis, social isolation, and guilt over their previous lifestyle. The authors suggest several recommendations for the primary care staff and psychiatric consultant in the psychological care of AIDS patients. This study consisted of psychological case reports of hospitalized San Francisco AIDS patients. Psychiatric consultations were prompted by the patient's request, by the primary physician's perception of unusual emotional or behavioral state and referral, or by the patient's presenting a management problem on the ward. Diagnoses were made according to DSM-III. A group of 13 from 40 patients with AIDS admitted to the wards of a large San Francisco hospital was seen by the staff of a psychiatric service following referral. Of this group, ll men were gay, and 2 were bisexual; they ranged in age from 24 to 42 years (average, 33.8). Eleven patients were white, one was black, and one was Hispanic. Six held college degrees; 11 were currently unemployed. 1) Treatment: General Support Care (Psychiatric) (IVA) 4A-Dil-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Perry, Samuel W., MD; Tross, Susan, PhD. Psychiatric Problems of AIDS Inpatients at the New York Hospital: Preliminary Report. Public Health Reports, March-April 1984, Vol. 99, No. 2: 200-205. Cornell University Medical College; New York Hospital; Memorial Sloan- Kettering Cancer Center, New York, New York. This study assessed the degree to which neuropsychiatric complications occurred among AIDS patients hospitalized during acute illness. Of the patients reviewed, a majority (83%) showed a mood disturbance, while 65% showed signs of organic mental syndrome. References to neuropsychiatric complications appeared in every patient's chart. Neurological complications were seldom explicitly diagnosed or treated. Psychiatric consultation was requested for 10 patients (19%) because of management problems, for diagnostic assessment, or by self-referral. The results suggest that neuropsychiatric complications of AIDS are underdiagnosed and psychiatric consultation is underutilized. Factors contributing to the heightened risk of psychological problems among AIDS patients are the threat to life, severe physical debilitation, central nervous system involvement, fear of contagion, disclosure of homosex- uality or drug abuse, and guilt associated with sexual transmission. A retrospective review of the charts of 52 AIDS patients in New York Hospital between | September 1981 and | September 1983 was conducted to determine the prevalence of recorded psychiatric complications and the use of psychiatric consultation. A total of 52 AIDS cases in New York were reviewed. The majority were middle-class homosexual men in their 30s. Specifically, 46 were homosexual or bisexual (5 of these were also intravenous drug users), 3 were Haitians, | was an intravenous drug user, and 2 (including the only female patient) denied belonging to any high-risk group. I) Treatment: General Support Care (Psychiatric) (IVA), 2) Central Nervous System Disease Infection (IID) 4A-Per-2 [V. Treatments for AIDS B. Symptom Management Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Leoung, Gifford S., MD; Mills, John, MD; Hopewell, Philip C., MD; Hughes, Walter, MD; Wofsy, Constance, MD. Dapsone-Trimethoprim for Pneumocystis carinii Pneumonia in the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, July 1986, Vol. 105, No. 1: 45-48. Medical Service, San Francisco General Hospital Medical Center, and Department of Medicine, University of California, San Francisco, California; St. Jude Children's Research Hospital, Memphis, Tennessee. All patients with AIDS and a first episode of Pneumocystis carinii pneumonia seen at the San Francisco General Hospital between November 1984 and April 1985 were evaluated for oral treatment with dapsone plus trimethoprim. All 15 patients who met the entry criteria improved clinically and radiographically (on X-rays) within 3 to 10 days after starting treatment. Repeat pulmonary function tests and lung scans after 3 weeks of therapy also showed improvement. Although side effects occurred in 14 patients, in only 2 were they severe enough to require stopping therapy. Both these patients had worsening skin rashes, and dapsone-trimethoprim therapy was stopped after 10 days. Compared with trimethoprim-sulfamethoxazole and pentamidine used in similar patients, oral dapsone-trimethoprim appears to be at least as effective, seems to be better tolerated, and may cause fewer serious side effects. An initial history and physical exam were done for all patients. The clinical determination of improvement or deterioration was based on the degree of dyspnea (shortness of breath) and frequency of coughing for each patient. Laboratory studies, including complete blood counts and serum chemistry panels, were done every 3 days, with urinalysis and chest X-rays done at admission and weekly thereafter. After 3 weeks of therapy, an induced-sputum or bronchoscopic exam was repeated. All patients were seen monthly after completion of treatment. Fifteen patients were included in this study, selected from a group of 37 patients with AIDS identified at the San Francisco General Hospital between 15 November 1984 and 5 April 1985, all of whom were 18 years or older and were having a first episode of P. carinii pneumonia. The remaining 22 patients were excluded for clinical reasons or because they did not agree to participate in the study. 1) Treatment: Symptom Management (IVB), 2) Diagnostic Definitions of AIDS: P. carinii Pneumonia (I[IA2) 4B-Leo-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Wharton, J. Marcus, MD; Coleman, Diana Lewis, MD; Wofsy, Constance B., MD; Luce, John M., MD; Blumenfeld, Walter, MD; Hadley, W. Keith, MD; Ingram-Drake, Leslie, AB; Volberding, Paul A., MD; Hopewell, Philip C., MD. Trimethoprim-Sulfamethoxazole or Pentamidine for Pneumocystis carinii Pneumonia in the Acquired Immunodeficiency Syndrome: A Prospective Randomized Trial. Annals of Internal Medicine, July 1986, Vol. 105, No. Ll: 37-44, Medical Service and Microbiology Laboratory, San Francisco General Hospital Medical Center; Departments of Medicine and Laboratory Medicine, University of California, San Francisco, California. Forty patients with AIDS experiencing their first episode of Pneumocystis carinii pneumonia were assigned at random to receive either trimethoprim-sulfamethoxazole or pentamidine isethionate. The two groups did not differ significantly in the severity of pulmonary or systemic abnormalities at enrollment. Five patients treated initially with trimethoprim-sulfamethoxazole and one patient treated initially with pentamidine died during the 21-day treatment period. No significant differences were seen between groups in rate of improvement, pulmonary function, or uptake of radioactive gallium by the lungs. Adverse reactions necessitated changing from the initial drug for 10 patients on trimethoprim-sulfamethoxazole and Il patients on pentamidine. Minor reactions occurred in all patients. The authors conclude that in patients with AIDS, trimethoprim- sulfamethoxazole and pentamidine are not significantly different in efficacy or in frequency of adverse reactions. This randomized clinical trial compared an established treatment (pentamidine) with a new regimen of trimethoprim-sulfamethoxazole in the treatment of P. carinii pneumonia in AIDS patients. Both clinical and laboratory evaluations were performed. The study included extensive initial evaluation to determine the comparability of the two treatment groups, analyses of early and long-term response to treatment, and quantitation of toxic effects from the drugs used. Forty patients, all of whom were seen at the San Francisco General Hospital Medical Center between July 1983 and April 1984, who had AIDS and were in their first episode of P. carinii pneumonia were evaluated. This group was selected from a total of 51 patients, Il of whom were considered ineligible for the study or did not agree to participate. 1) Treatments: Symptom Management ([VB), 2) Diagnostic Definitions of AIDS: P. carinii Pneumonia (IIIA2) 4B-Wha-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Stahl-Bayliss, Celine M., MD; Kalman, Concetta M., RN; Laskin, Oscar L., MD. Pentamidine-Induced Hypoglycemia in Patients with the Acquired Immune Deficiency Syndrome. Clinical Pharmacological Therapy, March 1986, Vol. 39, No. 3: 271-275. Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Cornell University Medical College, New York, New York. The effects of pentamidine-induced hypoglycemia on 37 AIDS patients with Pneumocystis carinii pneumonia (PCP) were studied. Ten patients (nine adults and one infant) developed hypoglycemia. At 27% of the sample, this is four times higher than the rate for immunosuppressed patients without AIDS. In four patients hypoglycemia occurred from | to 4 days after pentamidine treatment was discontinued. Hypoglycemia lasted for a mean of 10 days (range, | to 31 days). Nine of these patients had symptomatic hypoglycemia; eight developed central nervous system (CNS) symptoms or altered mental status (delerium or psychotic reactions). No other cause for CNS dysfunction was identified. One 40- year-old male patient developed permanent brain damage from hypoglycemia. All patients with pentamidine-induced hypoglycemia required therapy with intravenous 50% dextrose supplements. All of the hypoglycemic patients (100%) had renal failure, as did 35% of the group with normal blood glucose levels. The mean age of adult hypoglycemic patients was 39 years, similar to the mean age for patients who did not develop hypoglycemia (36 years). The clinical histories of 37 New York City AIDS/PCP patients who received pentamidine isethionate were examined. Each patient received a minimum of three doses; the daily dosage was 4 mg/kg given intravenously. The mean duration of therapy was 4 days. A group of 37 patients with PCP and AIDS treated from May 1982 to July 1984 at New York Hospital-Cornell Medical Center (33 adult males, 3 adult females, and | female infant) were studied. The mean adult age was 37 years (range, 24 to 57 years). The infant was 6 months old (perinatal AIDS). Each patient had not responded to or had an adverse reaction to trimethoprim-sulfamethoxazole (used for treating PCP). No patient who developed hypoglycemia had abnormal cortisol or thyroid functions. 1) Treatments: Symptom Management (IVB) 4B-Sta-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Volberding, Paul A., MD; Abrams, Donald I., MD; Conant, Marcus, MD; Kaslow, Kathleen, BA; Vranizan, Karen, MA; Ziegler, John, MD. Vinblastine Therapy for Kaposi's Sarcoma in the Acquired Immuno- deficiency Syndrome. Annals of Internal Medicine, September 1985, Vol. 103, No. 3: 335-338. Oncology Department, San Francisco General Hospital; Department of Dermatology, University of California; and Veterans Administration Hospital, San Francisco, California. This study evaluated a chemotherapeutic agent in treatment of Kaposi's sarcoma in AIDS (AIDS-KS). Intravenous vinblastine, 4 to 8 mg per week, used alone was used to treat 38 patients with AIDS-KS. The dose was calculated in relation to the patient's total leukocyte count. Ten patients had a measurable response, and 19 had stable disease during therapy. Apart from expected modest neutropenia, toxicity was minimal. A lower response rate was seen in patients with anemia, an elevated erythrocyte sedimentation rate (a gauge for determining the progress of an inflammatory disease), or any lymphomalike symptom. Opportunistic infections were common regardless of type of response but were more common in patients who did not respond to therapy. The median time from initiation of vinblastine therapy to a documented response was 5 weeks. The authors conclude that vinblastine used in low weekly doses is effective in treating AIDS-KS and has few toxic effects. Beginning in November 1981, patients with AIDS-KS who were not eligible for other clinical protocols were enrolled in this study at San Francisco General Hospital. This study was based on clinical record review. Patients were initially evaluated for several clinical and laboratory features considered prognostically relevant, including a careful medical history and physical examination, complete blood count, chemistry profile, and examination of feces for parasites and their eggs. Also, test tube immunologic studies were done for most patients, particularly T-cell subset analysis. Gastrointestinal endoscopy was done for some patients. \ Vinblastine was given weekly to patients; the initial dose was 4 mg per week, and the dose was increased weekly as long as, the total leukocyte count remained above approximately 2,500 cells/mm~. The median dura- tion of therapy was 20 weeks, and the median time from initiation of therapy to death or the time of this analysis (June 1984) has been 72 weeks. This study examined 38 AIDS-KS patients who were not eligible for other clinical protocols, who were treated weekly with vinblastine between November 1981 and March 1984. 1) Treatment: Symptom Management (IVB), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA) 4B-Vol-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Mintzer, David M., MD; Real, Francisco X., MD; Jovino, Louise, BA; Krown, Susan E., MD. Treatment of Kaposi's Sarcoma and Thrombocytopenia with Vincristine in Patients with the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, February 1985, Vol. 102, No. 2: 200-202. Clinical Immunology Service, Memorial Sloan-Kettering Cancer Center, New York, New York. The treatment experience with 23 patients with Kaposi's sarcoma (KS) related to AIDS who were treated with vincristine is described in this study. Of the 18 patients evaluable for response (five patients died after receiving only one or two doses of vincristine and were therefore considered inevaluable), all showed evidence of tumor regression. None had a complete response; 11 patients had a partial response and 7 had a minor response. The extent to which there was improvement in endobronchial and gastrointestinal disease is not reported. The median duration of partial response was 4+ months. Three patients who had a coexisting immune thrombocytopenia developed a significant increase in platelet count, which in two patients was sustained with continued treatment for 6 and 9 months. (Reviewer note: Others have found substantial neurotoxicity associated with this treatment.) The authors conclude that because of its marrow-sparing effects and antitumor efficacy, vincristine might be a reasonable drug to include in the treatment of AIDS patients with KS, in combination with other cytotoxic agents or biological response modifiers which are active against opportunistic infections, the commonest cause of death in AIDS patients with KS. Vincristine (2 mg) was given weekly by rapid intravenous infusion for 2 to 5 weeks and then every 2 weeks as tolerated. The dose was reduced to | mg for patients with moderate to severe neurotoxicity. Responses were classified as complete if there was no evidence of residual tumor, partial if tumor regression was greater than 50% but incomplete, and minor if there was definite evidence of tumor regression but less than 50% reduction of active lesions. Serial endoscopic examinations were not done routinely. Twenty-three patients with AIDS and KS were Included in the study; 18 were evaluable for response to therapy. All patients were homosexual or bisexual men. Their median age was 35 years. Ten patients had a history of opportunistic infection. Fourteen patients had biopsy-confirmed lymph node involvement, and 12 had endobronchial or gastrointestinal disease as shown by endoscopy. Three patients were considered to have immune thrombocytopenia. Of the 23 patients studied, 20 had been treated previously with recombinant leukocyte A interferon, 7 had received chemotherapy, and 10 had received radiation therapy. 1) Treatment: Symptom Management (IVB), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA) 4B-Min-5 Author(s): Title: Source: Institution: Findings: Method: Cooper, Jay S., MD; Fried, Peter R., MD; Laubenstein, Linda J., MD. Initial Observations of the Effect of Radiotherapy on Epidemic Kaposi's Sarcoma. Journal of the American Medical Association, 17 August 1984, Vol. 252, No. 7: 934-935. Departments of Radiology (Cooper, Fried) and Medicine (Laubenstein), New York University Medical Center, New York, New York. In light of the known sensitivity of classic Kaposi's sarcoma to modest doses of ionizing radiation, the authors selected lesions in patients who had AIDS, and they review their early experiences as well as document the radiosensitivity of the lesions found in the disease. Radiation therapy, in moderate doses, produced at least partial regression of disease in all instances. Nine lesions regressed completely after treatment. One patient who had complete regression experienced recurrence 7 months following radiation. Partial regression of the disease generally was noted midway through treatment. On the last day of therapy, the tumor remained visible in most cases, only to continue to resolve over the next few weeks to months. The four patients whose lesions were painful experienced substantial or complete symptomatic relief. Pain was notably less for all patients during the second week of treatment. Of the seven patients who had stage [A disease (visceral, with no systemic signs or symptoms) when treated, two remained apparently free of disease, two have experienced new lesions at other sites but remain locally controlled, one suffered local recurrence, and one has died of opportunistic infection. No complications of radiotherapy were observed, and the reaction to radiation of the adjacent normal tissues has been indistinguishable from that observed in other patients with AIDS. These authors suggest that this demonstrates the radiosensitivity of Kaposi's sarcoma seen in conjunction with AIDS. Modest doses of radiation, which entail little or no morbidity, can be expected to produce at least some regression of virtually all lesions and, in the majority of cases, to improve appearance and function and relieve pain. They also state that because patients were selected by criteria that made radiotherapy the treatment of choice, these results cannot be compared with those obtained by chemotherapy or immunotherapy. Some lesions were selected for treatment because the disease was sufficiently limited (stage I) that all lesions could be easily encompassed within a single radiation portal; it was hoped that treatment would render the patient disease-free for a prolonged interval. Other lesions were selected because they represented the only site among others (stage III or IV) that was disturbing to the patient because of pain, functional impairment, or substantial cosmetic defect. The staging system was as follows: [ -- cutaneous, locally indolent; II -- cutaneous, locally aggressive, with or without regional lymph node involvement; III -- generalized mucocutaneous (mucous membrane and skin) or generalized lymph node involvement of more than upper and lower extremities alone, including minimal gastrointestinal disease, defined as more than five lesions greater than 2 cm in diameter; [VA -- visceral, with no systemic 4B-Coo-6 Sample Size: Policy Keys: signs or symptoms; [VB -- visceral, with systemic signs such as 10% weight loss or an oral temperature of more than 38°C that was unrelated to an identifiable source of infection and lasted more than 2 weeks. Treatment plans were individualized in all cases. Follow-up was continued through 31 December 1983. The minimum duration of follow- up from cessation of radiation therapy was 3 months. Descriptive case findings were reported. Between | January 1981 and 30 September 1983, 182 men who had biopsy-proved Kaposi's sarcoma associated with a history compatible with AIDS were registered at the New York University Medical Center. Of this group, 15 had a total of 17 lesions considered best managed by ionizing radiation (radiation therapy for treatment of cancer). The patients ranged in age from 26 to 55 years. All were homosexual men, and seven manifested other evidence of altered immune function, principally opportunistic infection, in addition to tumors. 1) Treatment: Symptom Management (IVB), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA 1), 3) Disease Stages (IIIC) Author(s): Titles Source: Institution: Findings: Method: Sample Size: Gordin, Fred M., MD; Simon, Gwynn L., MD; Wofsy, Constance B., MD; Mills, John, MD. Adverse Reactions to Trimethoprim-Sulfamethoxazole in Patients with the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, April 1984, Vol. 100, No. 4: 495-499. Medical Services, San Francisco General Hospital and Department of Medicine, University of California, San Francisco, California. The relative toxicity of pentamidine isethionate and of trimethoprim- sulfamethoxazole, the only two agents that have been used to treat Pneumocystis carinii infections, was compared to investigate the higher rate of adverse reactions reported with trimethoprim-sulfamethoxazole in patients with AIDS than in other patient groups. Only 5 of 37 patients with AIDS who began taking trimethoprim-sulfamethoxazole were able to complete treatment. Drug toxicity occurred in 29 patients, and in 19 treatment was changed due to adverse reactions. Toxic effects occurred in 13 of 30 patients treated with pentamidine, but only 4 required a change in drug. Patients received trimethoprim-sulfamethoxazole for a median of 9.5 days and showed signs of toxicity sooner than with pentamidine, which patients received for a median of 12.5 days. Although trimethoprim-sulfamethoxazole has become the drug of choice for P. carinii infections because of its efficacy and safety, this study shows increased toxicity when used for patients with AIDS. This study suggests that, while further study is required to determine the relative efficacy and safety of these two drugs, pentamidine appears to be less toxic for treatment of P. carinii in patients with AIDS. Retrospective chart review was conducted of all patients with AIDS at San Francisco General Hospital who had been treated for P. carinii infection to determine the relative toxicity of trimethoprim- sulfamethoxazole and pentamidine in this population. Standard protocols were used to review charts; when toxic reactions were noted or treatment was discontinued, the clinical cause was determined and the notes of the physicians caring for the patient were used to determine whether the change was due to drug failure, adverse effects, or other reasons. The following information was recorded for both treatments: total days treated, drug toxicity (graded as either mild or severe by predetermined criteria), time that drug toxicity was first noted, and reason treatment was stopped. The sample included 38 male patients being tested for pneumocystosis between the ages of 22 and 45 years and admitted to either San Francisco General Hospital Medical Center or the University of California Hospitals, San Francisco, between October 1981 and April 4B-Gor-7 1983. Thirty-seven were homosexual, two of whom were also intravenous drug abusers. One patient denied having any recognized risk factors. Policy Keys: 1) Treatment: Symptom Management (IVB) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Update: Treatment of Cryptosporidiosis in Patients with Acquired Immunodeficiency Syndrome (AIDS). Morbidity and Mortality Weekly Report, 9 March 1984, Vol. 33, No. 9: 117-119, Centers for Disease Control, Atlanta, Georgia. In November 1982, 21 AIDS patients were reported with severe protracted diarrhea caused by cryptosporidiosis (infection with a protozoan parasite); no effective treatment was known at that time. Since then, 91 other AIDS patients with chronic cryptosporidiosis have been reported to the Centers for Disease Control. Although no therapy has been consistently effective, preliminary reports suggest that a few patients may have responded to treatment with spiramycin or the combination of quinine and clindamycin. Since December 1982, physicians at the University of Miami have used spiramycin to treat seven AIDS patients with cryptosporidiosis. Six others were treated with spiramycin at five other institutions, and one non-AIDS patient with cryptosporidiosis associated with a bone marrow transplant has received the drug. No adverse effects of the drug were noted. Three of the AIDS patients were apparently effectively treated after 3 to 4 weeks of spiramycin therapy. Follow-up 6 to 7 months later revealed that all three remained asymptomatic. Two have subsequently died from other AIDS-related causes. In an additional three AIDS patients, symptoms improved rapidly with spiramycin, but these patients continued to have cryptosporidia in their stools. After recurrence, two of these three again improved, but the third continued to have severe diarrhea and has since died. The non-AIDS patient also improved with spiramycin therapy. The remaining seven AIDS patients did not respond to spiramycin. Three, however, died within 2 to 7 days after starting treatment; none of the deaths was associated with the spiramycin. This report presents findings for 13 AIDS patients and one non-AIDS patient, all of whom had cryptosporidiosis and were treated with spiramycin. Findings are reported for 14 patients: 13 with AIDS-related and | with transplant-related cryptosporidiosis. Thirteen patients were adults, and one was a 2-year-old child. I) Treatments: Symptom Management (IVB), 2) Clinical Manifesta- tions: Opportunistic Infections (I11A2) 4B-Cen-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Haverkos, Harry W., MD, Coordinator, PCP Therapy Project Group. Assessment of Therapy for Pneumocystis carinii Pneumonia. The American Journal of Medicine, March 1984, Vol. 76: 501-508. AIDS Activity, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. Cases of Pneumocystis carinii pneumonia (biopsy-proven) were studied to determine the efficacy and safety of anti-Pneumocystis drug therapy. There was a longer time between onset and diagnosis for adult patients with P. carinii pneumonia secondary to AIDS. All patients received the standard treatments for their infections. There was no difference in survival rates through 90 days of follow-up between AIDS patients and adults with other known causes of immune deficiency. However, AIDS patients required longer therapy and had a higher rate of relapse. Failure of therapy with trimethoprim-sulfamethoxazole was found to be a poor prognostic sign. After failure with trimethoprim- sulfamethoxazole, addition of a second drug (pentamidine) did nothing to improve survival. Patients in both adult groups who were given the drug orally consistently did better than those treated intravenously. This was a retrospective analysis of cases of biopsy-proven P. carinii pneumonia reported to the Centers for Disease Control (CDC). Comparisons of outcome were made among three groups: 101 adults with AIDS, 31 patients whose immune systems were compromised by leukemia or immunosuppression for organ transplantation, and 150 pediatric cases. A total of 282 cases of biopsy-proven P. carinii pneumonia reported to the CDC by 19 U.S. medical centers were studied. Cases were 132 adults reported between | January 1979 and | September 1982 and 150 children from St. Jude Children's Research Hospital. 1) Treatment: Symptom Management (IVB), 2) Diagnostic Definitions of AIDS: P. Carinii Pneumonia (IlIA2), 3) Populations: Pediatric Cases (IAY) 4B-Hav-9 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Severe Neutropenia during Pentamidine Treatment of Pneumocystis carinii Pneumonia in Patients with Acquired Immunodeficiency Syndrome--New York City. Morbidity and Mortality Weekly Report, 17 February 1984, Vol. 33, No. 6: 65-67. Centers for Disease Control, Atlanta, Georgia. During November 1983, three patients at one New York City hospital who had AIDS and Pneumocystis carinii pneumonia (PCP) developed severe neutropenia while being treated with pentamidine. Since August 1981, 23 other patients with AIDS and PCP were treated with pentamidine at this hospital, and none had developed neutropenia unless another drug was given simultaneously. In another report forwarded to the Centers for Disease Control (CDC), of 179 patients with AIDS and PCP who were treated with pentamidine, 26 (14.5%) developed leukopenia. Case reports of the three initial subjects are presented. For each patient this was the first admission for PCP, and each showed clinical recovery; two recovered during therapy with pentamidine. The authors of this early study conclude that despite the short time between the onset of neutropenia and the administration of pentamidine and the gradual improvement of the neutropenia after cessation of drug treatment, it should not be presumed that these reactions were specifically related to pentamidine. (More recent evidence suggests, however, that neutropenia is a common toxocity associated with pentamidine.) Standard report forms for 179 patients with AIDS and PCP who were treated with pentamidine between January 1982 and September 1983 showed that 26 (14.5%) developed leukopenia, and in 12 cases the physician discontinued pentamidine for this reason. In six of these cases, neutropenia or granulocytopenia was specifically mentioned as a complication, although standard reporting forms were not sufficiently specific to characterize this phenomenon. Case reports of AIDS patients with PCP, suffering from neutropenia after administration of pentamidine, are presented. Standard report forms were also used to describe 179 patients treated with pentamidine between January 1982 and September 1983. This report describes three AIDS patients with PCP being treated with pentamidine in a New York City hospital and CDC reports for 179 patients with AIDS and PCP treated with pentamidine between January 1982 and September 1983. 1) Treatment: Symptom Management (IVB), 2) Diagnostic Definitions of AIDS: P. carinii Pneumonia (II[A2) 4B-Cen-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jaffe, Howard S.; Ammann, Arthur J.; Abrams, Donald I.; Lewis, Brian J.; Golden, Jeffrey A. Complications of Co-Trimoxazole in Treatment of AIDS-Associated Pneumocystis carinii Pneumonia in Homosexual Men. The Lancet, 12 November 1983, Vol. 2, No. 8359: 1109-1111. Department of Medicine, Pulmonary Division, Cancer Research Institute; Department of Pediatrics, University of California, San Francisco, California. This study examines the use of cotrimoxazole (trimethoprim plus sulfamethoxazole) in the treatment of Pneumocystis carinii pneumonia (PCP) in AIDS patients. Of 18 homosexual men with AIDS and PCP in this study who were treated with cotrimoxazole, 8 developed apparent drug-related complications, usually after 9 days of therapy. Symptoms included fever (7), rash (6), and cytopenias (reduction of cells in circulating blood) (5); all had increasing malaise, often with nausea and headaches. Symptoms usually developed after 9 days of cotrimoxazole therapy, abated in all patients soon after the drug was discontinued, and recurred in four patients who resumed cotrimoxazole therapy. Two children with AIDS and PCP were also treated with cotrimoxazole and developed the same symptoms. Cotrimoxazole therapy has been used widely for almost two decades. Adverse reactions occurred in only 91 of 1,121 (8%) of non-AIDS patients tested in another study, and symptoms were usually gastrointestinal reactions. Cytopenias, fever, and rash have occurred in very few patients during the two decades of use compared with the high frequency in this study. The rapid onset of side effects and their immediate return with resumption of therapy have not been seen in non-AIDS immunocom- promised patients with PCP. Case descriptions are presented for 8 of 18 patients who developed adverse reactions during treatment with cotrimoxazole. Daily doses of cotrimoxazole were 20 mg of trimethoprim and 100 mg of sulfamethoxazole per kg. Eight patients in a series of 18 homosexual men with AIDS and PCP, who were treated intravenously with cotrimoxazole and developed drug- related complications were studied. These eight were white and ranged in age from 25 to 45 years. Two children with AIDS and PCP are also described. 1) Treatments: Symptom Management (IVB) 4B-Jaf-11 [V. Treatments for AIDS C. Therapeutic Intervention l. Antiviral Therapy Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Vrang, Lotta; Oberg, Bo. PP; Analogs as Inhibitors of Human T-Lymphotropic Virus Type III Reverse Transcriptase. Antimicrobial Agents and Chemotherapy, May 1986, Vol. 29, No. 5: 867- 872. Department of Virology, Karolinska Institute, Stockholm, Sweden (Vrang); Department of Antiviral Chemotherapy, Research and Development Laboratories, Sodertalje, Sweden (Oberg). The identification of inhibitors of human T-cell lymphotropic virus type III (HTLV-II) reverse transcriptase which also inhibit HTLV-II replication in cell cultures is important to the development of antiviral therapies for AIDS. In this study, inorganic pyrophosphate (PP;) analogs were tested for inhibitory effects on HTLV-II reverse transcriptase. The structural requirements for inhibition and mechanism of action of the most active inhibitors -- foscarnet, ammonium-21-tungsto-9-antimonate, and 3'-azidothymidine triphosphate -- were also investigated. The structure-activity relationship for activity of PP; analogs against HTLV-II reverse transcriptase showed similarities to the effects on other reverse transcriptases. In all cases, foscarnet was the most active inhibitor. Different mechanisms of action were found among the inhibitors investigated in this study. The authors suggest that these differences might be of importance, and combinations could be used to prevent the development of resistance or to obtain synergistic effects. Study findings indicate that the use of reverse transcriptase inhibitors against HTLV-III infections is expected to prevent the infection of new cells, when reverse transcriptase is required, but not to eliminate virus from infected cells, in which viral RNA is synthesized by cellular enzymes. For permanent clinical use against HTLV-III infections, it will thus not be enough to inhibit reverse transcriptase; the treatment must also result in the elimination of infected cells. It seems likely that this can only be achieved by combinations of reverse transcriptase inhibitors and other drugs. Experiments were conducted with tissue culture medium from U937 cells infected with HTLV-Illg. Standard inhibition assays werb performed. Not applicable. 1) Treatment: Antiviral Therapy (IVC1) 4Cl1-Vra-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Koretz, Stuart H., MD, PhD, Study Director, and the Collaborative DHPG Treatment Study Group. Treatment of Serious Cytomegalovirus Infections with 9-(1,3-Dihydroxy- 2-Propoxymethyl)Guanine in Patients with AIDS and Other Immunodeficiencies. The New England Journal of Medicine, 27 March 1986, Vol. 314, No. 13: 801-805. Collaborative DHPG Treatment Study Group; Institute of Clinical Medicine, Syntex Research, Palo Alto, California (Koretz). The drug 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), which inhibits viral replication in vitro, was used to treat serious cytomegalovirus (CMV) infections in 26 patients with underlying immunodeficiency (including 22 with AIDS). The clinical status of 17 of 22 patients in whom CMV infection was virologically confirmed improved or stabilized, although in 4 of them some affected organs deteriorated or did not improve. Fourteen of 18 patients for whom adequate viral culture data were available showed clearing of CMV from all sites examined. Patients with CMV pneumonia often responded poorly; four of seven died before completing 14 days of DHPG therapy. The condition of Il of I3 patients with CMV retinitis and 5 of 8 with gastrointestinal disease stabilized or improved. However, clinical and virologic relapses occurred in 11 of 14 (79%) patients when DHPG was discontinued. Neutropenia was the most frequent adverse reaction. The authors conclude that DHPG offers promise for the therapy of severe CMV infections in some immunodeficient patients, but further study will be necessary to establish its efficacy and safety. (Reviewer note: FDA approval is expected soon.) Between 3 May and 15 December 1984, patients received DHPG on a "compassionate-use" basis for treatment of severe (life- or sight- threatening) CMV infections. Clinical and virologic investigations were conducted. DHPG was administered in doses of 5 mg/kg of body weight (2.5 mg/kg in one patient), infused intravenously over | hour at 8- to 12- hour intervals for a median of 14 days. Efficacy was assessed clinically and by follow-up cultures for CMV. The 26 patients in this study included 22 with AIDS, 2 with bone marrow transplants, | with severe combined immunodeficiency, and | receiving alkylating agents for myeloproliferative syndrome. I) Treatment: Antiviral Therapy (IVC1) 4C1-Kor-2 Author(s): Title? Source: Institution: Findings: Method: Sample Size: Policy Keys: Cooney, David A.; Dalal, Maha; Mitsuya, Hiroaki; McMahon, James B.; Nadkarni, Mohan; Balzarini, Jan; Broder, Samuel; Johns, David G. Initial Studies on the Cellular Pharmacology of 2',3'-Dideoxycytidine, an Inhibitor of HTLV-III Infectivity. Biochemical Pharmacology, 1986, Vol. 35, No. 13: 2065-2068. Developmental Therapeutics Program (Cooney, Dalal, McMahon, Nadkarni, Johns), Clinical Oncology Program (Mitsuya, Balzarini, Broder), Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. The pharmacological properties of the compound 2',3'-dideoxycytidine (ddCyd), the most potent of 2',3'-dideoxynucleosides that have been found to inhibit the in vitro infectivity and cytopathic effect of human T-cell lymphotropic virus type IlI/lymphadenopathy-associated virus (HTLV- III/LAV), were examined. In other retrovirus test systems, the activity of this group of compounds has been attributed to the sensitivity of the retroviral reverse transcriptase, and the relative resistance of cellular DNA polymerase a, to inhibition by the biologically active dideoxynucleotides derived from the nucleosides. Findings in the present study are compatible with the supposition that this interpretation applies to HTLV-II also. Results do not support an alternate hypothesis that HTLV-III-infected T lymphocytes are more efficient than other cells in generating the active dideoxynucleoside triphosphate inhibitor. This report describes results of several in vitro and in vivo studies of ddCyd. Methods are provided in detail for each study. Not applicable. 1) Treatment: Antiviral Therapy (IVC1) 4C1-Coo-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Broder, Samuel; Collins, Jerry M.; Markham, Phillip D.; Redfield, Robert R.; Hoth, Daniel F.; Groopman, Jerome E.; Gallo, Robert C.; Yarchoan, Robert; Lane, H. Clifford; Klecker, Raymond W.; Mitsuya, Hiroaki; Gelmann, Edward; Resnick, Lionel; Myers, Charles E.; Fauci, Anthony S. Effects of Suramin on HTLV-III/LAV Infection Presenting as Kaposi's Sarcoma or AIDS-Related Complex: Clinical Pharmacology and Suppression of Virus Replication in Vivo. The Lancet, 21 September 1985, Vol. 2, No. 8456: 627-630. National Cancer Institute, Bethesda; National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland; Walter Reed Army Medical Center, Washington, DC; New England Deaconess Hospital, Boston, Massachusetts; Mount Sinai Hospital Medical Center, Miami Beach, Florida. In this clinical trial, the drug suramin, which impairs the in vitro infectivity and inhibits the cytopathic effect of human T-cell lymphotropic virus type III (HTLV-II) or lymphadenopathy-associated virus (LAV), was given to 10 outpatients with AIDS presenting as Kaposi's sarcoma (KS) or as AIDS-related complex (ARC). The commonest physical side effects associated with suramin included fever and erythematous skin eruptions. Three patients had a burning sensation of the skin, particularly in the extremities. All side effects were self- limiting and subsided despite continuing therapy and rising plasma suramin levels. In four patients who could be assessed, the drug inhibited replication of HTLV-III when plasma levels of 100 ug/ml (micrograms per mililiter) were attained. Suramin did not, however, produce clinical or immunological improvement with the regimen used in this study. (Reviewer note: Subsequent investigation of longer term regimens have produced extreme toxicity.) Suramin was given on an outpatient basis. Most patients received a total dose of 6.2 g -- a test dose of 200 mg on day 0, followed by l-g doses on days 3, 7, 14, 21, 28, and 35, each dose being given intravenously over 20 minutes. Plasma samples from patients | to 4 were obtained for measurement of suramin levels just before and the day after each dose; predose samples were obtained from the other patients. After the last dose, samples were obtained at intervals of | week or longer. Peripheral blood mononuclear cells were assayed for replicating HTLV-IIl. Plasma suramin levels were determined by a high-pressure liquid chromatograph- ic procedure. Plasma half-life was determined for the monoexponential disappearance of drug following the end of therapy. The subjects were 10 homosexual or bisexual white males aged 23 to 53 years. Six patients had AIDS with KS, and four patients had ARC. All natients were seropositive for HTLV-II and gave their informed consent to participate in this trial. 1) Treatment: Antiviral Therapy (IVC1) 4C1-Bro-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: McCormick, Joseph B.; Mitchell, Sheila W.; Getchell, Jane P.; Hicks, Donald R. Ribavirin Suppresses Replication of Lymphadenopathy-Associated Virus in Cultures of Human Adult T Lymphocytes. The Lancet, 15 December 1984, Vol. 2, No. 8416: 1367-1369. Division of Viral Diseeases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. This study tested the in vitro effect of ribavirin, an antiviral drug which has been used extensively for the treatment of human virus infections, on the replication of lymphadenopathy-associated virus (LAV). Data from this study suggest that ribavirin inhibits the replication of LAV in human adult T lymphocytes in vitro. Various dilutions of ribavirin were tested; significant suppression of virus replication by higher concentrations (50 and 100 ug/ml) was observed during the first week of infection. The lowest effective in vitro dose was in the range of 30 to 50 ug/ml. After a week of suppression following initial ribavirin treatment, virus replication began to increase on the 8th or 9th day after infection. Further study, which showed an increase in reverse transcriptase (RT) by virus infected cells within 5 days, indicated that the drug had its effect on viral replication without irreversibly affecting cell function. The authors caution that while it is reasonable to use in vitro drug levels as general guidelines for effective drug doses, the in vivo dose requirement may be very different. Initial data from this report are encouraging, but whether these early laboratory experiments are predictive of a positive clinical effect in patients is not known. (Reviewer note: Subsequent experiments do not appear to show positive results.) Replication of LAV was tested at various dilutions of ribavirin and monitored by testing for RT. Viral antigen expression was detected by a direct immunofluorescence test. Cells were innoculated with virus, and RT levels were monitored. Not applicable. 1) Treatment: Antiviral Therapy (IVC1) 4C1-McC-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Grieco, Michael H., MD; Reddy, Mohan M., PhD; Manvar, Dolly, MD; Ahuja, Kishore K., MD; Moriarty, Mary L., BS. In-Vivo Immunomodulation by Isoprinosine in Patients with the Acquired Immunodeficiency Syndrome and Related Complexes. Annals of Internal Medicine, August 1984, Vol. 101, No. 2: 206-207. St. Luke's-Roosevelt Hospital Center, New York, New York. The results of a pilot open trial of the effects of in vivo Isoprinosine (methisoprinol), an agent that has been shown to increase certain proliferative responses of normal human lymphocytes, on immunologic values in AIDS and related syndromes are reported. Preliminary results by various test approaches suggest that Isoprinosine may enhance mitogen-induced (concanavalin A and phytohemagglutinin) lymphocyte proliferative responses in patients with complexes related to AIDS. If these findings are confirmed, further trials in a larger group of patients with AIDS-related complexes would be required to establish immunologic effectiveness, appropriate dosage, and mechanisms involved. A long- term controlled study would be necessary to prove clinical efficacy. The authors indicate that Isoprinosine is relatively safe and potentially could be administered on a long-term basis. [soprinosine was administered in a dose of 4g per day for 4 weeks after written informed consent was obtained from patients. Blood samples were drawn to analyze T lymphocyte markers for OKT4 and OKT8 just before treatment, on the l4th day 28th day of treatment, and l4 days after discontinuation of treatment. Lymphocyte proliferative responses to mitogens were also measured, except for the 14th day. All patients had been clinically stable for at least 4 weeks at the beginning of treatment. Peripheral blood mononuclear cells were isolated and analyzed, and T- cell subsets were determined by indirect immunofluorescence. Lymphocyte responses were determined by various culture techniques. Responses were analyzed statistically. The patient population included four patients with AIDS-related complexes (one with diarrhea, three with lymphadenopathy) and five meeting the Centers for Disease Control definition of AIDS. 1) Treatment: Antiviral Therapy (IVC1) 4C1-Gri-6 Author(s): Title: Source: Institution: Findings: Method: Groopman, Jerome E., MD; Gottlieb, Michael S., MD; Goodman, Jesse, MD; Mitsuyasu, Ronald T., MD; Conant, Marcus A., MD; Prince, Harry, PhD; Fahey, John L., MD; Derezin, Marvin, MD; Weinstein, Wilfred M., MD; Casavante, Conrad, PhD; Rothman, John, PhD; Rudnick, Seth A., MD; Volberding, Paul A., MD. Recombinant Alpha-2 Interferon Therapy for Kaposi's Sarcoma Associated with the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, May 1984, Vol. 100, No. 5: 671-676. Departments of Medicine, Microbiology, and Immunology, University of California School of Medicine, Los Angeles, California; Departments of Medicine, Dermatology, Laboratory Medicine, and Immunology, University of California School of Medicine, San Francisco, California; Schering Corporation, Bloomfield, New Jersey. The toxicity and efficacy of recombinant alpha-2 interferon, a possible therapeutic agent for AIDS-related Kaposi's sarcoma (KS) because of its known antiviral, immunoregulatory, and antiproliferative properties, was examined in this randomized prospective study. High or low doses of recombinant alpha-2 interferon were administered to 20 patients for 5 days per week, every other week, for four treatment cycles. Therapy was well tolerated subjectively and caused only mild hematologic and hepatic toxicity at both dose levels. No consistent or sustained changes were seen in immunologic variables during or after treatment. Six patients with KS, four at the high dose and two at the low dose, had objective responses (complete or partial) to treatment. However, therapy did not appear to eradicate cytomegalovirus (CMV) or prevent opportunistic infections related to CMV. The authors of this article state that their results differ from those of a previous study (Krown et al., 1983), which reported a modest increase in patients' mean T-cell ratios after 3 weeks of daily treatments. The present authors conclude that alpha-2 interferon at these doses does not appear to be a broadly effective antiviral agent in patients with AIDS, but that studies in more patients may elucidate the immune variables predictive of ether response to alpha-2 interferon or relative resistance to opportunistic infection. Recombinant alpha-2 interferon is an active agent in therapy for KS-related AIDS, and further clinical testing should determine its optimal dose and schedule for this disorder. In this prospective, open-I1 stydy patients were randomly Senad 7, eithey high doses (50 x 10 iP , intravenously) or low doses (1 x 10 U/m#, subcutaneously) of alpha-2 interferon for 5 days per week, every other week, for four treatment cycles. Patients not responding to the low dose were offered the option of using the high dose. Response was assessed after three and four treatment cycles (6 and 8 weeks on the study). Patients responding to a given dose were maintained at that dose, with therapy given on 5 consecutive days every 3 to 4 weeks. The patients were followed up for 12 to 18 months after treatment. Detailed medical and sexual histories were obtained for all patients including physical examination with quantitation and measurement of 4C1-Gro-7 Sample Size: Policy Keys: skin lesions, palpation and measurement of lymph nodes, and upper and lower endoscopy. All patients had extensive laboratory evaluations at entry; immune function was assessed in vivo and in vitro for all patients. Natural killer cell activity was measured in some patients. These measurements were continued during follow-up for all patients. Response was recorded during and after interferon treatment, using standard oncologic criteria. Complete response was defined as disappearance of all lesions, and partial response as a decrease of 50% or more in the sum of the areas of at least three to five bidirectionally measured index lesions. Minimal response was defined as a less than 50% decrease in this sum. Progression was defined as the appearance of new lesions during therapy, even if other lesions decreased in size. Twenty men with biopsy-proven KS who met the Centers for Disease Control (CDC) criteria for AIDS were examined in a study that had been approved by the Human Subject Protection Committees of the University of California-Los Angeles and the University of California-San Francisco. Mean age of subjects was 36 years (range, 24 to 56). The lifestyles and medical history of the group were similar in terms of lifetime number of sexual partners (median, 1,000; range, 75 to 4,000), illicit drug use (90% used marijuana, 60% cocaine, 50% nitrites), and history of sexually transmitted diseases (history of gonorrhea, syphilis, genital herpes, and hepatitis B in more than half the group) to those of patients with AIDS reported to CDC. All patients had a life expectancy of 6 months or greater. 1) Treatment: Antiviral Therapy, Immunomodulators (IVCIL,2), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA 1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Gold, Jonathan W.M.; Leyland-Jones, Brian; Urmacher, Carlos; Armstrong, Donald. Pulmonary and Neurologic Complications of Treatment with FIAC (2'Flouro-5-lodo-Aracytosine) in Patients with Acquired Immune Deficiency Syndrome (AIDS). AIDS Research, 1984, Vol. |, No. 4: 243-252. Infectious Disease Service and Clinical Immunology Service, Department of Medicine, and Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York. Both severe ulcerative herpes simplex virus infections and disseminated cytomegalovirus (CMV) infections are common in AIDS patients. This study describes the treatment complications of seven patients with AIDS who received the antviral agent 2'-fluoro-5-iodo-aracytosine (FIAC) for herpesvirus infections. FIAC is very potent and effective in vitro and in vivo against herpes simplex virus types | and 2. It is also active against varicella-zoster virus (VZV) and CMV in vitro. Of 11 patients with AIDS who received FIAC, seven developed neurologic toxicity, which was reversible, or had the acute onset or sudden, rapid progression of disseminated CMV infections. Reversible neurotoxicity consisting of tremulousness, startle myoclonus, slurred speech, confusion, and either agitation or lethargy was seen in three patients and resolved within 2 days after FIAC treatment was discontinued. Significant pulmonary complications were seen repeatedly in 5 patients but did not occur in the remaining 6 of 11 patients, nor was significant neurotoxicity observed in the other 8 of ll patients. In spite of these toxic effects, clinical improvement was seen in three patients following treatment with FIAC. The authors note that neurotoxicity (tremor and lethargy) has also recently been reported in immunocompromised patients treated with acyclovir. Although these neurologic changes are probably directly drug related, the possibility of a deleterious synergistic effect of an antiviral agent on subclinical central nervous system viral infection, i.e. drug- related toxicity, cannot be ruled out. They conclude that antiviral therapy in patients with AIDS should be undertaken with caution. This was an uncontrolled study of FIAC treatment effects. CMV infections were documented by detecting viral inclusion bodies in biopsy specimens and by isolating virus. VZV infections were documented by virus isolation from typical vesicular skin lesions. Following the protocol for treatment of herpes zoster in immunccomprenised hosts, FIAC was given in doses of 200 to 300 mg/m“ twice daily for 7 days. Complications in 7 of 11 patients treated with FIAC are described. Seven patients with AIDS and Kaposi's sarcoma (one patient) or opportunistic infections suggestive of defective cell mediated immunity but no recognizable cause of immune deficiency (six patients) were described. Six were homosexual men and one was a female intravenous drug user. Their ages ranged from 24 to 41 years. The seven patients 4C1-Gol-8 described for this study were among 11 patients with AIDS treated for herpesvirus infections with FIAC. Policy Keys: 1) Treatment: Antiviral Therapy (IVC1) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Tsang, Peter H.; Tangnavarad, Khanitha; Solomon, Stephen; Bekesi, J. George. Modulation of T- and B-Lymphocyte Functions by Isoprinosine in Homosexual Subjects with Prodromata and in Patients with Acquired Immune Deficiency Syndrome (AIDS). Journal of Clinical Immunology, 1984, Vol. 4, No. 6: 469-478. Department of Neoplastic Diseases, Mount Sinai School of Medicine, New York, New York. To gain a better understanding of its therapeutic efficacy, if any, and mode of action, the restorative effect of the antiviral agent [soprinosine (methisoprinol) on the impaired function of lymphocytes derived from patients with AIDS and male homosexuals with prodromal symptoms was examined. Initial findings for prodromal male homosexuals, patients with AIDS, and healthy male heterosexual controls demonstrated significant immunological abberations in both the homosexual males and the AIDS patients, but by different degrees. A significant decrease in the number of circulating T lymphocytes and in the helper/suppressor (T4/T8) T-cell ratio was shown. Both the absolute number and the percentage of helper T cells were reduced markedly in the homosexual population and to an even greater degree in the AIDS patients. (The authors note that results expressed as absolute numbers more accurately reflected patients' immunologic status than percentage values.) Proliferative responses to a T-cell mitogen (phytohemagglutinin) and T-cell-dependent B-cell mitogen (pokeweed mitogen) were severely impaired in prodromal subjects and more so in the AIDS group. The response to pokeweed mitogen was unrelated to the total number of suppressor T cells but was associated with a significant decrease in helper T cells. Incubation of lymphocytes with Isoprinosine selectively restored function in lymphocytes from immunosuppressed subjects. The degree of stimulation for lymphocytes among homosexuals with normal lymphocyte functions was comparable to that for control subjects, although a higher degree of augmentation was achieved in lymphocytes from AIDS patients and prodromal subjects with impaired blastogenic responses. For none of the AIDS patients with severe immunodeficiencies, however, was lymphocyte function restored to the normal range established for heterosexual controls. Comprehensive clinical and immunological testing was performed for all study groups. A series of experiments to test the effects of [soprinosine were conducted and analyzed statistically. Analyses included examination of lymphocyte separation, analysis of mononuclear cells for surface markers, and determination of lymphocyte function by mitogenic stimulation. Three groups were examined in this study: 94 homosexual males (average age, 37.3 ears), 23 clinically diagnosed AIDS patients (average age, 38.5 years), of whom 4 had Pneumocystis carinii pneumonia and 19 had Kaposi's sarcoma, and a control group of 118 apparently healthy heterosexual males (average age, 42.5 years). 4C1-Tsa-9 Policy Keys: 1) Treatment: Antiviral Therapy (IVC1) [V. Treatments for AIDS C. Therapeutic Intervention 2. Immunomodulators Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Bonavida, Benjamin; Katz, Jonathan; Gottlieb, Michael. Mechanism of Defective NK Cell Activity in Patients with Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related Complex. The Journal of Immunology, 15 August 1986, Vol. 137, No. 4: 1157-1163. Department of Microbiology and Immunology (Bonavida, Katz), and Department of Medicine (Gottlieb), University of California School of Medicine, Los Angeles, California. Abnormalities in both T-cell-mediated cytotoxicity and natural killer (NK) cell activity have been reported in AIDS patients. This study investigated the mechanism by which NK cell activity in patients with AIDS and AIDS-related complex (ARC) is depressed. Further investigation was conducted to observe whether the immunomodulator interleukin 2 (IL-2) could restore the functional activity of NK cells. Previous studies by these authors on the mechanism of NK cell-mediated cytotoxicity (NKCMC) suggest that NKCMC is a multistage process. First, the NK cell recognizes and binds to its target. Next, the target cell delivers a signal to the NK effector cell, which activates the release of NK cytotoxic factors (NKCF). These factors bind to the membrane of the target cell and mediate target cell lysis. Impaired NKCMC can result from defects in NK cell number, recognition of target, NKCF response or release, or NKCF action. Results presented here and elsewhere suggest that the defect in NK activity is not due to depletion of NK cells or to a defect in target cell recognition, but rather to a postrecognition event. In particular, results suggest that AIDS and ARC patients’ NK cells are defective in the trigger involved in release of NKCF. Evaluations of treatment response with IL-2 suggest that the trigger for NKCF production and the cytolytic function of the patients' NK cells are regulated by IL-2. By delineating the stage at which AIDS and ARC patients' NK cells are defective, the authors state that it will be possible to monitor their recovery and to investigate the effect of various biologic response modifiers in restoring NK activity. Blood samples were collected from healthy normal donors and from AIDS and ARC patients. Mononuclear cells were isolated. A variety of cell cultures and assays were used for analysis. Blood samples were obtained from patients with AIDS, none of whom had Kaposi's sarcoma, and patients with ARC, who were homosexual or bisexual males with persistent generalized lymphadenopathy and antibody to human T-cell lymphotropic virus type Ill, and normal controls. 1) Treatment: Immunomodulators (IVC2) 4C2-Bon-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Pompidou, A.; Delsaux, M.C.; Telvi, L.; Mace, B.; Coutance, F.; Falkenrodt, A.; Lang, J.M. [soprinosine and Imuthiol, Two Potentially Active Compounds in Patients with AIDS-Related Complex Symptoms. Cancer Research, September 1985, Vol. 45 (Suppl.): 467 1s-467 3s. Hopital Saint-Vincent de Paul, Paris, France (Pompidou, Delsaux, Telvi, Mace); Centre de Transfusion Sanguine de Strasbourg, Strasbourg, France (Falkenrodt, Lang). [soprinosine (methisoprinol) and Imuthiol (sodium diethyldithiocarbamate) are Immunomodulators with a unique effect on T cells: both are considered T-cell inducers and are responsible for an increase in OKT4+ cells. To evaluate the possibility of their use to restore immune function in patients with AIDS-related complex (ARC), this study examined the in vitro effects of these drugs. The influence of in vivo treatment with Imuthiol of three ARC patients is also presented as a preliminary report. [soprinosine and Imuthiol significantly increased both the percentage and absolute number of T4 cells in vitro. No changes in T8 cells were noted. Three homosexual ARC patients treated with Imuthiol showed clinical improvement (in terms of adenopathy and opportunistic infection regression) without any deleterious effects, and restoration of response to recall antigens was observed in all three patients. One patient exhibited a complete restoration of normal T-cell profiles. A previous report (Tsang et al., 1984) has shown a beneficial effect of [soprinosine in pre-AIDS patients. However, the best way to administer the drug without causing immunosuppression after long-term treatment must still be established. Imuthiol caused a short-term improvement in three ARC patients without any side effects. Those findings, combined with the results of the present study, indicate the need for more data on the effects of these two immunomodulating agents in AIDS patients. Because of the absence of deleterious effects, these agents can be proposed for use in AIDS patients in assocation with direct antival agents and for the preventive treatment of seropositive subjects, particularly those with a decrease in T4 cells. The drugs may also be beneficial to seropositive hemophiliacs. Peripheral blood mononuclear cells were studied in vitro by several culture preparation techniques. The in vivo effects of Imuthiol were alsc tested in homosexual male patients. These patients were treated with Imuthiol (5 to 10 ug/kg per week) for 4 to 6 months. In vitro studies used mononuclear cells obtained from six homosexual men, ages 25 to 35 years, with ARC and from an unspecified number of normal controls. Three ARC patients were evaluated to assess the effects of Imuthiol in vivo. 1) Treatment: Immunomodulators (IVC2) 4C2-Pom-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Preble, Olivia T.; Rook, Alain H.; Steis, Ronald; Silverman, Robert H.; Krause, David; Quinnan, Gerald V.; Masur, Henry; Jacob, Joan; Longo, Dan; Gelmann, Edward P. Interferon-Induced 2'-5' Oligoadenylate Synthetase during Interferon-a Therapy in Homosexual Men with Kaposi's Sarcoma: Marked Deficiency in Biochemical Response to Interferon in Patients with Acquired Immunodeficiency Syndrome. The Journal of Infectious Diseases, September 1985, Vol. 152, No. 3: 457- 465. Department of Pathology, Uniformed Services University of the Health Sciences; Division of Virology, National Center for Drugs and Biologics; Medicine Branch, National Cancer Institute; Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland. To evaluate factors influencing responsiveness to human alpha interferon (IFN-a) therapy, used for treatment of Kaposi's sarcoma (KS) in patients with AIDS, this study examined 28 homosexual men who received 1- to 6- month courses of antineoplastic (antitumor) therapy with IFN-a as well as homosexual and heterosexual controls. Fifteen of 28 patients and two of seven healthy homosexual men had high endogenous levels of 2',5'- oligoadenylate (2-5A) synthetase. IFN therapy induced further increases in this enzyme in only 10 of the 28 patients with AIDS. Peripheral blood cells from all but one of the patients with AIDS and the homosexual controls tested were markedly deficient in their ability to respond to IFN in vitro, as measured by increased levels of 2-5A synthetase. No statistical relationship was found between cytomegalovirus (CMV) viremia and pretherapy endogenous circulating IFN or between disseminated CMV infection and either basal levels of 2-5A synthetase or changes in level during therapy. Pretherapy circulating IFN was associated with progressive KS during therapy, but rises in the level of 2- 5A synthetase were not sufficient to predict a good clinical response. Serum and heparinized peripheral blood samples were obtained from patients and controls. The first nine patients received IFN-a (7.5 x 10 U/m intramuscularly (I.M.) daily for 28 days. Ten patients received 15 x 10” U/m” LM. daily for 10 days, followed by a 10-day rest and then another 10 days of therapy. Nine patients started therapy at 22.5 x 10 U/m” LM. per day, and patients with evidence of a clinical response (decrease in size of KS lesions) were continued on IFN therapy for | to 6 months. Peripheral blood samples were obtained for all patients at different times before and during therapy to estimate minimum titers of circulating IFN. Additional testing procedures included IFN assays, 2-5A synthetase assay, and cultures of urine, throat washings, and blood for the presence of CMV. Twenty-eight homosexual men with biopsy-proven KS and AIDS were studied under protocol at the National Institutes of Health Clinical Center, beginning in December 1981. Eight had prior opportunistic infections. Seven homosexual controls, two of whom had antibody to human T-cell lymphotropic virus type III but no clinical signs of disease, 4C2-Pre-3 were also studied. Normal controls included six men and four women who were healthy, heterosexual laboratory personnel not working with AIDS specimens. Policy Keys: 1) Treatment: Immunomodulators (IVC2), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA 1) Author(s): Title: Source: Institution: Findings: Method: Frederick, Winston R.; Epstein, Jay S.; Gelmann, Edward P.; Rook, Alain H.; Armstrong, Gary R.; Djeu, Julie Y.; Jackson, Lozannie; Manischewitz, Jody F.; Enterline, Joan; Jacob, Joan; Masur, Henry; Quinnan, Gerald V., Jr. Viral Infections and Cell-Mediated Immunity in Immunodeficient Homosexual Men with Kaposi's Sarcoma Treated with Human Lymphoblastoid Interferon. The Journal of Infectious Diseases, July 1985, Vol. 152, No. 1: 162-170. Division of Virology, Office of Biologics Research and Review, Center for Drugs and Biologics, Food and Drug Administration; Medicine Branch, National Cancer Institute; Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland. Herpesvirus infections and cellular immunity were studied in 19 patients with AIDS who were treated with human lymphoblastoid interferon (L- IFN) for Kaposi's sarcoma (KS). Infections with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were nearly universal among these patients. Treatment with L-IFN did not reduce active viral infection by CMV or EBV, although administration of L-IFN in this study was associated with tumor regression in 2 of 19 patients. During therapy a reduction in natural killer cell (NKC) activity was observed, and in vitro responsiveness to IFN was lost. No measurable improvement in immunologic status was associated with administration of L-IFN. The authors suggest that the lack of a direct antiviral effect in these patients may have been due to the high virus burden, especially in individuals with viremia. Further work is needed to explain why L-IFN administration caused depression of NKC activity and failed to augment virus-specific human leukocyte antigen (HLA)-restricted T-cell responses. The authors conclude that exogenous IFNs may still play a useful role in the therapy or prevention of AIDS when the function of IFNs in this disease is better understood. This study was an open-label, two-armed trial of L-IFN treatment of patients with AIDS-related KS. The treatment protocol compared high- dose and low-dose regimens. Nine patients received daily intramuscular injections of 7.5 x 10” U of L-IFN per m*; eight received a 28-day course of treatment and one received a 9-day course of treatment because of rapidly progressing pulmonary KS. The two patients with evidence of tumor regression at the end of the first 28 days continued to receive treatment with L-IFN at the same dose 3 days a week for an additional 6 weeks. A second group of 10 patients received a daily dose of 15 x 10 U of L-IFN per m® intramuscularly for 20 days on a schedule of 10 days of therapy followed by 10 days without therapy and then a final 10 days of therapy. Studies to detect antibodies to CMV and EBV were performed before, during, and after therapy. Additional testing procedures included IFN assays, T-cell enumeration, cytotoxic lymphocyte assays, and lymphocyte proliferation assays. 4C2-Fre-4 Sample Size: Policy Keys: Nineteen homosexual men with biopsy-proven KS who met the Centers for Disease Control definition of AIDS were studied. They ranged in age from 22 to 52 years (mean, 35.3 years); 16 were white and 3 were black. All subjects gave informed consent as approved by the National Cancer Institute's Clinical Research Subcommittee. 1) Treatment: Immunomodulators (IVC2), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA1) Author(s): Title: Source: [nstitution: Findings: Method: Sample Size: Policy Keys: Fauci, Anthony S., MD; Masur, Henry, MD; Gelmann, Edward P., MD; Markham, Phillip D., PhD; Hahn, Beatrice H., MD; Lane, H. Clifford, MD. The Acquired Immunodeficiency Syndrome: An Update. Annals of Internal Medicine, June 1985, Vol. 102, No. 6: 800-813. National Institutes of Health, Bethesda, Maryland. AIDS continues to be a major public health problem in the U.S., and recently its worldwide spread has accelerated. The syndrome is now known to be caused by a human retrovirus (human T-cell lymphotropic virus type III, HTLV-II) transmitted by sexual contact and by blood or blood products. The virus has been isolated from blood and other body tissues and fluids, including brain, semen, and saliva. Although AIDS in the U.S. is still largely confined to male homosexuals and intravenous (I.V.) drug users, there is increasing evidence, particularly from Zaire (central Africa), that the virus can be spread by heterosexual contact. Therapeutic attempts at immune system reconstruction with lympho- cytes and lymphokines (chemical factors produced by T-cells that target bacteria-destroying cells to the site of infection) have resulted in some temporary improvement in immune function but no clinical effect; this indicates the need for specific antiretroviral therapy (the means of which have yet to be discovered) in combination with immune system reconsti- tution. This article is an edited summary of a conference of the Combined Clinical Staffs. A total of 6,720 U.S. cases of AIDS had been reported to the Centers for Disease Control as of 5 November 1984. The 6,294 male patients included 4,901 homosexuals or bisexuals, 915 [.V. drug users, 209 Haitians, 46 hemophiliacs, #2 transfusion-associated cases, 4 heterosexual contact cases, and 176 cases with no known risk factor. The 426 female patients included 239 LV. drug users, 35 Haitians, 35 transfusion associated cases, 46 heterosexual contact cases, and 71 cases with no known risk factor. 1) Treatments: Immunomodulators (IVC2), 2) Treatments: Antiviral Therapy (IVC1) 4C2-Fau-5 Author(s): Title: Source: Institution: Findings: Method: Gelmann, Edward P., MD; Preble, Olivia T., PhD; Steis, Ronald, MD; Lane, H. Clifford, MD; Rook, Alain H., MD; Wesley, Margaret, PhD; Jacob, Joan, MSN; Fauci, Anthony, MD; Masur, Henry, MD; Longo, Dan, MD. Human Lymphoblastoid Interferon Treatment of Kaposi's Sarcoma in the Acquired Immune Deficiency Syndrome: Clinical Response and Prognostic Parameters. The American Journal of Medicine, May 1985, Vol. 78: 737-741. Medicine Branch, Biostatistics and Data Management Section, Division of Cancer Treatment, National Cancer Institute; Department of Pathology, Uniformed Services University of the Health Sciences; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases; Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland. This study reported results for 30 consecutive patients with AIDS who were treated with intramuscular human lymphoblastoid interferon for Kaposi's sarcoma (KS). Of the 30 patients treated, three showed a complete regression of disease and one a partial regression of disease (13% response rate). An additional three showed a minor response. The responses were not dependent on drug dose. Both pretherapy total lymphocyte count and absolute numbers of helper T cells were associated with clinical outcomes. The presence of opportunistic infections or cytomegalovirus (CMV) viremia was associated with a poorer clinical response. Patients who had endogenous acid-labile alpha interferon prior to therapy were more likely to have progressive disease during interferon administration, although the reason for this was not clear. Although the initial rationale for interferon use in AIDS-related KS was based on both its immunomodulatory and antiviral effects and its antiproliferative effects, the authors found no evidence for any effect of interferon beyond objective tumor regression. They conclude that while this does not rule out some immunomodulation not measured in the laboratory, these results support previous studies which attribute the efficacy of interferon in KS to the drug's antiproliferative properties. These results also suggest that patients with KS and AIDS who have a more intact immune system are more likely to benefit from interferon therapy by manifesting a clinical response. Whether this response improves survival is an unanswered question that awaits appropriate randomized studies. Pretreatment evaluation included chest X-ray, abdominal computed tomographic scanning, lymph node examination by angiography, rigid sigmoidoscopy, and in vitro immunologic studies. Urine, saliva, and blood samples were cultured for CMV; bone marrow was routinely examined microscopically and cultured for organisms. Patients were divided, into three groups. The first 10 patients received interferon at 7.5 x 10° U/m* per day for 28 days; the next 10 received 15 x 10” U/m* per day for 10 days, followed by a 10-day rest and then 3 second 10 days at the same dose; the third group received 25 x 10° U/m 4C2-Gel-6 Sample Size: Policy Keys: per day for 28 days. One patient in the lowest-dose group received only two days of therapy because of rapidly progressive pulmonary KS and was not evaluated for response. Response was assessed weekly by measurement of existing lesions or by a search for the appearance of new lesions. Toxicity was graded on a scale of I to IV by leukocyte count, platelet count, liver enzymes, or creatinine, or by clinical assessment of neurologic or gastrointestinal toxicity. Statistical analysis was carried out to assess response to therapy or disease progression. Thirty consecutive male homosexual patients with AIDS were studied; responses to therapy were evaluated in 29 of these patients. All 30 patients had biopsy-proved KS confirmed by histologic review, and none had received prior interferon therapy. Patients ranged in age from 19 to 53 years. All gave informed consent as approved by the Institutional Review Board of the National Cancer Institute. 1) Treatment: Immunomodulators, Antiviral Therapy (IVC2,l), 2) Diagnostic Definition of AIDS: Kaposi's Sarcoma (IIIA) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Ho, David D.; Rota, Teresa R.; Kaplan, Joan C.; Hartshorn, Kevan L.; Andrews, Charla A.; Schooley, Robert T.; Hirsch, Martin S. Recombinant Human Interferon Alfa-A Suppresses HTLV-III Replication in Vitro. The Lancet, 16 March 1985, Vol. 1, No. 8429: 602-604. [Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. The effects of recombinant human alpha-A interferon (rIFN-aA) on human T-cell lymphotropic virus type III (HTLV-II) in normal peripheral blood mononuclear cells (PBMC) were studied in vitro. Single-dose vyIFNaA had no antiproliferative effect on PBMC even at a concentration of 1024 units/ml. However, a dose-related suppressive effect on HTLV- [IT replication was observed: both single-dose and multiple-dose regimens inhibited the virus. Inhibitory concentrations (4 to 1,024 U/ml) were not toxic to PBMC in culture and were within the ranges achievable in blood after injection. Three additional experiments (not presented) with PBMC from other normal donors confirmed these findings. Multiple doses of yIFNaA had no antiproliferative effect on PBMC. Low concentrations of yIFNaA reduced antigen positivity and reverse transcriptase activity, and 256 units/ml completely suppressed HTLV-III replication. The authors believe that these study findings suggest that clinical trials of rIFN-aA in early HTLV-III infection are warranted. Target cells were PBMC donated by healthy HTLV-IlI-seronegative individuals. HTLV-II was grown in H9 cells and titrated on normal PBMC. A cytopathic-effect reduction method was used to assay rIFN- aA. HTLV-II antigen expression was determined by indirect immunofluorescence testing with an HTLV-IlI-positive human serum, and reverse transcriptase activity was measured. Not applicable. 1) Treatment: Immunomodulators (IVC2) 4C2-Ho-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Rook, Alain H.; Hooks, John J.; Quinnan, Gerald V.; Lane, H. Clifford; Manischewitz, Jody F.; Macher, Abe M.; Masur, Henry; Fauci, Anthony S.; Djeu, Julie Y. Interleukin 2 Enhances the Natural Killer Cell Activity of Acquired Immunodeficiency Syndrome Patients through a y-Interferon-Independent Mechanism. The Journal of Immunology, March 1985, Vol. 134, No. 3: 1503-1507. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (Rook, Lane, Fauci); Clinical Ophthalmic Immunology Section, National Eye Institute (Hooks); Laboratory of Pathology, National Cancer Institute (Macher); Critical Care Medicine Department, Clinical Center, National Institutes of Health (Masur); Division of Virology, Center for Drugs and Biologics, Food and Drug Administration (Quinnan, Manischewitz, Djeu), Bethesda, Maryland. Patients with AIDS exhibit a variety of disorders of cellular immunity, including a deficient ability to generate suppressor T cells and depressed levels of natural killer (NK) cell activity. Interleukin 2 (IL-2) can markedly improve these depressed immune functions in vitro. Because IL-2 can induce the release of gamma interferon (IFN-y) from normal peripheral blood lymphocytes, and because IFN-y may play a role in the regulation of NK cell activity, this study was performed to determine whether IL-2 enhancement of the NK cell activity of AIDS patients occurs indirectly through the modulation of IFN-y or directly through an IFN-y-independent effect. Study results indicated that the peripheral blood lymphocytes from patients with AIDS usually do not release IFN-y when cultured with IL-2 and that IL-2 enhancement of the NK cell activity of these patients may be an IFN-y-independent event (and may have potential clinical rele- vance). The authors suggest that because patients with AIDS exhibit a marked defect in their ability to produce IFN-y, both in response to IL-2, as this study demonstrated, and in response to a variety of recall microbial antigens such as Toxoplasma gondii and Candida albicans, protocols which provide for the combined use of IL-2 and IFN-y may be beneficial for the therapy of AIDS. A therapeutic regimen could be developed that includes two lymphokines which could simultaneously augment important immune functions, but perhaps by two independent mechanisms. Peripheral blood lymphocytes were obtained from whole blood and studied for their ability to release IFN-y in response to IL-2 at a concentration of 100 U/ml. Antiviral activity was determined, and assays for NK cell activity were done. The patient group consisted of nine male homosexuals with a clinical diagnosis of AIDS based on the Centers for Disease Control's definition of AIDS. Two patients had Kaposi's sarcoma and seven had had previous life-threatening opportunistic infections. All patients gave consent and were participating in peer-reviewed National Institutes of Health protocols. Eight healthy heterosexual subjects served as controls. 4C2-Roo-8 Policy Keys: 1) Treatment: Immunomodulators (IVC2) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Clumeck, N.; Van de Perre, P.; Mascart-Lemone, F.; Cran, S.; Bolla, K.; Duchateau, J. Preliminary Results on Clinical and Immunological Effects of Thymopentin in AIDS. International Journal of Clinical Pharmacology Research, 1984, Vol. 4, No. 6: 459-463. Department of Immunology, St. Pierre Hospital, Brussels, Belgium (Clumeck, Van de Perre, Mascart-Lemone, Cran, Duchateau); Cilag Ltd., Schaffhausen, Switzerland (Bolla). The purpose of this study was to evaluate in AIDS patients the effect of thymopentin, a synthetic pentapeptide, with an activity similar to the natural hormone thymopoietin. Thymopentin has been used as an immunomodulator to modify immune reactivity in various congenital immune disorders. The results of thymopentin therapy in 10 African patients with AIDS are reported. Six patients with AIDS or lymphadenopathy showed a significant increase in OKT3 and OKT8 cells after direct intravenous (L.V.) thymopentin injections. After LV. thymopentin infusion, blastogenic response to phytohemagglutinin (PHA) for these patients increased compared with pretherapy values and with values after direct L.V. injections. At the end of infusion therapy, skin tests became positive for three antigens. All six patients noted subjective improvement associated with significant weight gain and disappearance of fever. In contrast, the clinical and immunological status of the four patients with AIDS and opportunistic infections worsened during therapy, and two patients died from opportunistic infections. The authors believe that this preliminary study suggests that I.V. infusion with thymopentin may be useful in the early phase of AIDS as it produces symptomatic and immunological improvement. (Reviewer note: These have not been confirmed.) In this open study patients with AIDS were treated with I.V. thymopentin (50 mg) three times a week for 2 consecutive months: | month by direct [.V. injections and | month by 30-minute I.V. infusions. Immunological studies performed before, during, and after therapy included lymphocyte count, T-cell subset assessment, study of blastogenic response of lymphocytes to PHA, and delayed-type hypersensitivity skin testing for five antigens. Ten African patients with full-blown AIDS or AIDS-related lymphadeno- pathy were enrolled in this pilot study. Six patients (four females and two males) had AIDS lymphadenopathy. The other four patients (two females and two males) had AIDS and opportunistic infections. None of the 10 patients showed clinical or pathological evidence of any underlying immunodepressive disease or had a history of immunosuppres- sive therapy. A control group for the immunological studies consisted of 20 healthy black African volunteers matched for age and sex. 1) Treatment: Immunomodulators (IVC2) 4C2-C1lu-9 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Hauser, G.J.; Bino, Tamar; Rosenberg, H.; Zakuth, Vera; Geller, E.; Spirer, Z. Interleukin-2 Production and Response to Exogenous Interleukin-2 in a Patient with the Acquired Immune Deficiency Syndrome (AIDS). Clinical and Experimental Immunology, 1984, Vol. 56: 14-17. Department of Pediatrics, Pediatric Immunology Unit and Department of Anesthesiology and ICU, Tel-Aviv Medical Center; Tel Aviv University and the Israel Institute for Biological Research, Ness-Ziona, Israel. This study evaluated the response in vitro of T lymphocytes from an AIDS patient to stimulation by a blood protein, interleukin 2 (IL-2) and compared it with that for two normal subjects. For the two control subjects, the T lymphocytes responded by proliferating, as expected. For the AIDS patient, no proliferation was seen. Normal production of IL-2 by the white cells of the control subjects and the AIDS patients was found. The authors postulate that the underlying defect in the white blood cells of this AIDS patient may be a defect in a receptor for [L-2 on the white blood cell surface. A single case with two controls was reported from the Tel-Aviv Medical Center and the Israel Institute for Biological Research, Ness-Ziona, Israel. Peripheral blood mononuclear cells were obtained from the blood of patients as well as from a normal control and healthy donors. Cells were cultured and examined using a variety of methods. Blood samples from a 39-year-old homosexual male with Pneumocystis carinii pneumonia and AIDS and two control patients were studied. No dates for patient accrual are available. 1) Treatment: Therapeutic Interyention (IVC2), 2) Immunological Aspects (IIE) 4C2-Hau-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lane, H. Clifford; Siegel, Jay P.; Rook, Alain H.; Masur, Henry; Gelmann, Edward P.; Quinnan, Gerald V.; Fauci, Anthony S. Use of Interleukin-2 in Patients with Acquired Immunodeficiency Syndrome. Journal of Biological Response Modifiers, 1984, Vol. 3, No. 5: 512-516. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases; Critical Care Medicine, Clinical Center, and Medicine Branch, National Cancer Institute, National Institutes of Health; Division of Virology, Office of Biologics, Food and Drug Administration, Bethesda, Maryland. This study evaluated the use of a purified protein component of normal human blood called interleukin 2 (IL-2) in the treatment of 12 patients with AIDS. No clinical response to treatment with IL-2 administered intravenously was seen in any of the patients. Minimal toxic effects were noted during treatment with IL-2, including abnormal blood clotting and proteinuria. No new opportunistic infections developed in any of the patients while they were receiving this treatment. Changes in immune status were detected in some of the patients and included (1) a return of reaction to specific skin tests for immune reaction, (2) a decrease in the number of suppressor T cells, and (3) a decrease in immunoglobulin levels. The authors believe that while IL-2 has not been shown to be effective in the treatment of patients with AIDS, the fact that IL-2 can modulate the human immune system in vivo raises the possibility that with further study it may prove to be of value in the treatment of immunologically mediated diseases. This was a prospective, uncontrolled study of IL-2 treatment in AIDS patients. Immunologic studies were performed before, during and after therapy. Patients received a single, 2-hour infusion for single-dose toxicity and pharmacokinetic studies. Four days later they were put on a continuous infusion schedule which consisted of 5 days continuous therapy per week for 4 weeks. Doses ranged from 250 to 250,000 units. Twelve patients with AIDS, who had a lymphocyte count of less than 1,000 and either Kaposi's sarcoma or recovery from Pneumocystis carinii pneumonia, were studied. 1) Treatment: Therapeutic Intervention (IVC2) 4C2-Lan-11 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Lotze, Michael T.; Robb, Richard J.; Sharrow, Susan O.; Frana, Lesley W.; Rosenberg, Steven A. Systemic Administration of Interleukin-2 in Humans. Journal of Biological Response Modifiers, 1984, Vol. 3, No. 5: 475-432. Surgery Branch and Immunology Branch, National Cancer Institute, Bethesda, Maryland (Sharrow); Glenolden Laboratories, E.I. du Pont, Glenolden, Pennsylvania (Robb). This report describes results in 12 patients who were treated with purified (but non-recombinant) human interleukin 2 (IL-2) derived from the JURKAT cell line (E.l. du Pont de Nemours Co.) to assess toxicity, half-life, and possible therapeutic or immunologic effects in patients with cancer unresponsive to standard therapy and in patients with AIDS. The serum half-life of JURKAT IL-2 in humans was approximately 6 minutes. At higher doses of IL-2 a second component of clearance with a half-life of 30 to 120 minutes was found. Acute toxicity was minimal and consisted of headache in 6 patients, nausea in 4 patients, malaise in 6 patients, and fever and chills in 8 patients. No evidence of puimonary, hematologic, or renal toxicity or any evidence of autoimmune phenomena was detected. A transient elevation of bilirubin in the blood was seen in two patients receiving 2 mg of purified IL-2. No demonstrable effect on tumors or chronic immunodeficiency (AIDS) was seen. No consistent chronic immunologic effects were seen on a week-to-week basis during or following therapy. Acute changes in lymphokine responsiveness, the ability to generate lymphokine-activated killer cells, and an increase in macrophages in the mononuclear cells were noted following IL-2 administration. The authors state that more prolonged administration of IL-2 may be required to reverse the abnormal T-cell ratio and cytotoxic capacity seen in AIDS. Whether IL-2 will play a role in the treatment of malignant disease or acquired immunodeficiencies or following cancer chemotherapy will be the focus of future investigations. Patients received 0.25, 2.5, or 25 ug of IL-2 per kg by intravenous (I.V.) bolus over 5 minutes or as a continuous 24-h L.V. infusion on a weekly basis for 4 weeks. Vital signs were monitored closely during and after completion of each dose. Prior to infusion, a complete history was taken and a physical examination with careful measurement of tumor deposits was carried out. Serologic and immunologic testing was performed. T- cell markers were assayed by flow microfluorometry. Twelve patients (7 men, 5 women), ranging in age from 22 to 69 years, were enrolled in this protocol. This study group included two patients with melanoma, four patients with sarcoma metastatic to the lung, one patient with colorectal cancer metastatic to the lung, and five patients with AIDS and cutaneous Kaposi's sarcoma. All patients signed informed-consent forms and were selected after failure of standard radiation therapy or chemotherapy. 4C2-Lot-12 Policy Keys: 1) Treatment: Immunomodulators (IVC2) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Valone, Frank H.; Payan, Donald G.; Abrams, Donald I.; Dohlman, Jan G.; Goetzl, Edward J. Indomethacin Enhances the Proliferation of Mitogen-Stimulated T Lymphocytes of Homosexual Males with Persistent Generalized Lymphadenopathy. Journal of Clinical Immunology, 1984, Vol. 4, No. 5: 383-387. Howard Hughes Medical Institute, University of California, San Francisco, California (Valone, Payan, Dohlman, Goetzl); Department of Medicine, University of California Medical Center, San Francisco, California (Valone, Payan, Abrams, Dohlman, Goetzl). This study examined the ability of indomethacin to enhance T lymphocyte function in vitro. Indomethacin is an inhibitor of cyclooxygenase, an enzyme necessary for the synthesis of prostaglandin E, (PGE,). It has been suggested that endogenous PGE, may cause defective lymphocyte function in some patients with impaired immunity. Thus, it was of interest to determine whether suppression of PGE, with indomethacin might improve T-lymphocyte function in patients immunosuppressed by AIDS-related illnesses. The concentration of PGE, in material derived from patients’ lymphocytes was significantly higher than that in controls, consistent with a causative role of PGE, in the suppression of immune function. Treatment with indomethacin increased the proliferation of T lymphocytes from five of eight patients, but from none of 12 healthy homosexual and heterosexual control subjects. This increase was accompanied by a fall in lymphocyte-derived PGE, suggesting that this response was attributable to inhibition of cyclooxygenase activity. Because prolonged exposure to indomethacin suppresses the activities of diverse cellular enzymes and inhibits the effects of other leukocyte mediators derived from arachidonic ‘acid, this enhanced T-lymphocyte proliferation may not result from suppression of PGE, synthesis but rather from suppression of a different mediator, such as 4 entotriene By» which also suppresses T-lymphocyte proliferation. The authors conclude that abnormalities of the cyclooxygenase pathway of T lymphocytes in patients with the reactive lymph node syndrome may reflect an immunoregulatory defect which predisposes to infections and may evolve into the more severe abnormalities of AIDS. T-lymphocyte responses to mitogen were examined in vitro. Mononuclear leukocytes were recovered from patients and normal subjects. Human T lymphocytes and monocytes were isolated and assessed. T-lymphocyte proliferation and oxygenation of arachidonic acid were also assessed. PGE, was detected by radioimmunoassay. Eight patients were studied from a group of over 200 male homosexual patients with lymphadenopathy syndrome or AIDS followed at the Moffitt-Long Hospital and the San Francisco General Hospital of the University of California. All eight patients had intermittent fevers and 4C2-Val-13 Policy Keys: malaise associated with longstanding lymphadenopathy, and all were clinically immunosuppressed as evidenced by recurrent localized infections, including oral candidiasis (3), lymphadenitis (3), sinusitis (3), tinea corporis (5), amoebiasis (6), herpes zoster (3), and recurrent upper respiratory infections (6). No patient had had a life-threatening systemic fungal, protozoal, or viral infection. Controls included 30 homosexual and heterosexual subjects. 1) Treatment: Immunomodulators (IVC2) Author(s): Title: Source: Institution: Findings: Method: Volberding, Paul; Valero, Ruben; Rothman, John; Gee, Gayling. Alpha Interferon Therapy of Kaposi's Sarcoma in AIDS. Annals New York Academy of Sciences, 1984, Vol. 437: 439-446. San Francisco General Hospital, San Francisco, California Wonme Gee); Schering-Plough Corporation, Kenilworth, New Jersey (Valero); Hoffmann-La Roche, Nutley, New Jersey (Rothman). This report reviews the experience in treating AIDS-associated Kaposi's saroma (KS) with recombinant human alpha interferon, an agent found to have demonstrated antiviral and immunomodulatory activity. Previous studies have suggested that interferon may augment the host immune response in patients with AIDS and may have an antineoplastic effect against KS. Of five low-dose patients in the first protocol, there was one complete response, two partial responses, one patient with stable disease, and one with progressive disease. In the high-dose patient group, three achieved partial response, one achieved stable disease, and one had progressive disease. In this protocol it appeared that the clinical effectiveness of high-dose intravenous interferon was substantial. In the second protocol, 20 patients were treated with high-dose intravenous alpha interferon. Complete response was observed in two (10%), partial response in six (30%), and stable disease in 2 (10%). In 10 patients (50%), disease progressed despite therapy. A third protocol was used in which 30 patients were treated with a moderately high dose of subcutaneous interferon three times per week. Preliminary results imply that subjective toxicity with this route and schedule is more of a problem than with intravenous administration, but do not imply more serious objective toxicity in response rates, which were comparable to those with high-dose interferon. These early studies suggest that alpha interferon can be an effective antineoplastic agent in AIDS-associated KS. However, the authors consider the results disappointing in that no immune augmentation was documented and no clinically significant degree of protection against opportunistic infections was observed. In these trials, alpha interferon appeared to act directly as an antineoplastic agent and not through immune augmentation. In addition, its toxic effects, while tolerable for most patients, were not insignificant. The authors are nonetheless encouraged by the study findings and believe that alpha interferon can be useful for the patient population discussed and should receive further applications. Three clinical tests were compared: (1) a randomized trial of a low dose of alpha interferon administered subcutaneously compared with a high dose of the drug administered intravenously, (2) a larger group of patients treated with the high-dose intravenous schedule of the first trial, and (3) patients treated with a similarly high dose of alpha interferon, but administered subcutaneously. 4C2-Vol-14 Sample Size: Policy Keys: Patients at San Francisco General Hospital were selected for alpha interferon therapy if they had biopsy-proved KS and AIDS and were less than 60 years of age. All stages of KS were included. Ten patients were studied in protocol 1; 20 patients were studied in protocol 2; and 30 patients were included in protocol 3. All patients had an estimated life expectancy of more than 24 weeks. 1) Treatment: Immunomodulators, Antiviral Therapy (IVC2,1), 2) Diagnostic Definitions of AIDS: Kaposi's Sarcoma (IIIA) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Mittelman, Abraham, MD; Krown, Susan E., MD; Cirrincione, Constance, MS; Safai, Bijan, MD; Oettgen, Herbert F., MD; Koziner, Benjamin, MD. Analysis of T Cell Subsets in Cancer Patients Treated with Interferon. The American Journal of Medicine, December 1983, Vol. 75, 966-972. Memorial Sloan-Kettering Cancer Center, New York, New York. In this investigation of treatment effects, T-cell subsets were analyzed in 33 patients with advanced cancer who were treated with one of two interferon preparations: leukocyte interferon and a highly purified recombinant (produced by genetic engineering techniques) interferon. Included in the latter group were eight patients with immunodeficiency and Kaposi's sarcoma. With both interferon preparations, the mean (average) helper/suppressor T-cell ratio decreased 24 hours after the first interferon dose. Within the leukocyte interferon group, the decrease in the ratio was related to an increase in suppressor-cytotoxic T-cells; in the highly purified recombinant interferon group, it was accompanied by a small decrease in the proportion of helper-inducer T- cells that was greater than the decrease in suppressor-cytotoxic T- cells. Patients treated with highly purified recombinant interferon were monitored for the first 3 weeks of therapy. Most patients treated with the highly purified recombinant form, at all dose levels, had a decrease in helper/suppressor T-cell ratios on day 1. No substantial change in the ratio was observed on days 7, l4, and 22. Patients with immunodefi- ciency and Kaposi's sarcoma had responses similar to those of patients with other cancers treated with the highly purified form. In conclusion the authors state that although both leukocyte interferon and highly purified recombinant interferon induce immediate decreases in the helper/suppressor T-cell ratio, the T-cell subset(s) primarily responsible for the decrease varies with the source of interferon. Nine patients were treated with human leukocyte interferon at varyious doses for 28 days. Twenty-four patients were treated for 28 days with highly purified recombinant interferon intramuscularly at varyious dosage levels. White blood cell counts, lymphocyte counts, and T-cell subsets were measured before treatment with interferon (day 0) and 24 hours after the first interferon dose (day 1) for all patients. Patients peripheral blood mononuclear cells were examined for number and viability. T-cell populations were studied in 8 of 24 patients treated with highly purified recombinant interferon. The ratio of helper/ suppressor T-cells was determined and used to analyze the balance between the helper/suppressor T-cell subpopulations. Thirty-three adult patients with advanced cancer treated with interferon at Memorial Hospital in New York City from 1980 to 1982 were studied. In the group given partially purified human leukocyte interferon there were 5 males and 4 females, and the group given highly purified recombinant interferon consisted of 18 males and 6 females. In the first group the median age was 48 years (range, 20 to 65 years). In the second group the median age was 51 years (range, 25 to 71 years). The 4C2-Mit-15 individuals in both groups had various diagnoses, including breast, colon, and lymph node cancers as well as Kaposi's sarcoma and leukemia. Policy Keys: 1) Treatments: Immunomodulators (IVC2), 2) Immunological Aspects (IIE), 3) Clinical Manifestations: Kaposi's Sarcoma (IIIA) — ea = V. Risk Reduction A. Information/Education Il. Public Awareness Author(s): Title: Source: Institution: Findings: Silvestre, Anthony, MA; Lyter, David W., MD; Rinaldo, Charles R., Jr., PhD; Kingsley, Lawrence A., DrPH; Forrester, Randall, BA; Huggins, James, MSW, ACSW. Marketing Strategies for Recruiting Gay Men into AIDS Research and Education Projects. Journal of Community Health, Winter 1986, Vol. 11, No. 4: 222-232. Departments of Infectious Diseases and Microbiology (Silvestre, Rinaldo), Medicine (Lyter, Kingsley); Pathology (Rinaldo), University of Pittsburgh, Pittsburgh, Pennsylvania. This paper describes the concepts, strategies, and methods used to recruit volunteers for the Pitt Men's Study, a prospective surveillance study of human immunodeficiency virus (HIV) in homosexual and bisexual men in Pittsburgh, Pennsylvania. The goal of the Pitt Men's Study was to enroll at least 1,000 primarily healthy gay men, including a represen- tative sample of nonwhite gay men and significant numbers of econo- mically disadvantaged men and men who consider themselves bisexual. Seeking such a diverse population meant not relying on men who frequented gay organizations and bars or who read gay publications. Such men tend to be exclusively gay, relatively affluent, white, and well educated, whereas homosexuals as a whole, according to Kinsey (Sexual Behavior in the Human Male, 1948), do not differ significantly from heterosexuals by race, class, residence, and other demographic markers. The promotional campaign that was developed was based on several principles: packaging of the study to emphasize its immediate benefits (monitoring one's health, contributing to the community's welfare) and to reduce the costs (fear of disclosure or facing the threat of AIDS) for volunteers; creating a product (public health education) that the target groups valued and that would attract volunteers; establishing the main clinic in a way that would minimize volunteers’ apprehension about public exposure and instituting a traveling clinic which regularly visited places where gay men gathered; developing an aggressive promotional campaign which used a large number of techniques to inform men about the study; emphasizing personal contact through phone banks and other methods; monitoring volunteers' responses in exit interviews and questionnaires to permit effective evaluation of and adjustment to the recruitment program. Results showed that 66% of the men identified friends as their source of information about the study; 41% received their information from the regional gay newspaper, 34% from posters in bars, 24% from brochures distributed in bars, 23% from television, 20% from referral by physician or other professional, and 12% from posters on buses, radio ads, and classified ads in nongay publications combined. More than 1,700 gay and bisexual men were successfully recruited into the program between May 1984 and June 1986. The group included 7% nonwhites, comparable to the 6.7% nonwhite population overall in the Pittsburgh metropolitan area. The study also included a significant number of unemployed (8.7%) and part-time employed (12.5%). These 5A1-Sil-1 Method: Sample Size: Policy Keys: numbers are comparable to their representation in the larger commun- ity. In addition, 32% of the men characterized themselves as bisexual, which has significant epidemiological implications. A social marketing strategy was used to promote recruitment of gay and bisexual men in Pittsburgh into a prospective surveillance study of HIV. Recruitment was based on the marketing concepts of Kotter (Marketing for Nonprofit Organizations, 1976), which have been developed and promoted for use by nonprofit organizations. This study, called the Pitt Men's Study, was part of the Multicenter AIDS Cohort Study (MACS), a collaborative effort funded by the National Institutes of Health among four centers in Pittsburgh, Baltimore, Los Angeles, and Chicago to study the natural history of AIDS. Methods of promotion and the resulting mix of volunteers are described. A total of 1,718 gay and bisexual men from the Pittsburgh area were recruited. Their mean age was 32 years (range, 18 to 72), they had lived in Pittsburgh a mean of 20 years, 115 (7%) were nonwhite, 977 (57%) were college graduates, 248 (14%) were students, 1,158 (67%) were working full-time, and 546 (32%) were bisexual. 1) Information/Education: Recruitment of Homosexual Volunteers (VAL,2), 2) Populations: Homosexuals (IA1) Author(s): Title: Source: Institution: Findings: Williams, Linda Stewart. AIDS Risk Reduction: A Community Health Education Intervention for Minority High Risk Group Members. Health Education Quarterly, Winter 1986, Vol. 13, No. 4: 407-421. Detroit Health Department, Health Education Division, Detroit, Michigan. This report documents the development of an AIDS community education intervention by the Detroit Health Department, with particular focus on addressing gaps in AIDS education and information in the black male homosexual-bisexual population and the intravenous (I.V.) drug abuse population. Surveys of each group were conducted to provide information about awareness of AIDS prevention relevant to program design and implementation. [.V. drug abusers appeared to be relatively knowledgeable about AIDS. Over 75% of the I.V. drug abusers identified gay or bisexual males as at high risk for AIDS, and 62% also described I.V. drug abusers as a high-risk group. Seventy of 98 respondents (72%) correctly identified semen and blood as the principal modes of transmission. At the same time, 56 respondents (57%) stated that they were not concerned that they might get AIDS even though they correctly identified [.V. drug abusers as a high-risk group. When asked to identify ways in which a person could prevent spread of AIDS, 66 (67%) cited avoidance of [.V. drug abuse, and 67 (68%) identified not sharing needles as an effective prevention technique. More than 50% of the respondents were unaware of where to call to get information about AIDS and felt that adequate information was not readily available. Almost all respondents (92 of 98) agreed that drug abuse treatment centers should provide clients with AIDS information. Preliminary findings of an AIDS informational survey among the black homosexual population revealed the need for substantially greater educational efforts, at least among "grass roots" homosexuals. Twenty- three of 62 individuals surveyed (37%) identified Haitians as a high-risk group for AIDS, and more than half identified [.V. drug abusers as being at risk for AIDS. Twenty-seven (44%) of those interviewed were either not sure or unaware of where to call if they had questions about AIDS. Restricting sexual activity to one sexual partner and getting medical check-ups often were cited most frequently as preventive actions that homosexuals could take to reduce the likelihood of contracting AIDS. Only eight (13%) of the respondents correctly identified the AIDS virus as being transmitted through blood and semen. Only 12 persons thought that they might get AIDS. Approximately 37% reported they were not worried about possible infection. The authors discuss the development of information and education strategies and stress that the psychosocial aspects of AIDS are as confounding as the biomedical aspects. Without reliable and valid measures of the beliefs, attitudes, and practices of these two groups and 5A1-Wil-2 Method: Sample Size: Policy Keys: other minorities, interventions may fail to adequately address the needs or concerns of the population. Two AIDS informational surveys were conducted to obtain data about AIDS awareness among I.V. drug abusers and black homosexual men. This report includes findings from a survey administered to 98 clients enrolled in four methadone maintenance programs in the Detroit area and a similar survey conducted among 62 black homosexuals in Detroit during a 4-week interval in the late fall of 1985. 1) Information/Education: Public Awareness (VAL), 2) Populations: Minorities (IA5), 3) Populations: [.V. Drug Abusers (IA2) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Morton, A.D., BSC; McManus, I.C.,MD, PhD. Attitudes to and Knowledge about the Acquired Immune Deficiency Syndrome: Lack of a Correlation. British Medical Journal, 8 November 1986, Vol. 293: 1212. Department of Psychology, University College London, London, England. To see whether factual information could be effective in modifying public attitudes about AIDS, a questionnaire was distributed to preclinical medical students asking about knowledge of AIDS, attitudes toward homosexuality, and religious and political views. On the scale for knowledge of AIDS, the subjects had a mean score of 21.5 correct out of 36 items. The scale for attitude toward homosexuality (18 items) had a possible range of scores of 18 to 90, with high scores indicating positive attitudes towards homosexuals and homosexuality. Subjects scored a mean of 61.4. Attitudes about AIDS and its treatment did not correlate with knowledge about the condition, but instead were related to attitudes in general about homosexuality. The authors conclude that to reduce prejudice and increase public awareness about AIDS, there should be greater emphasis on general education about homosexuality than on the specific, factual details of the disease. Anonymous questionnaires were used to examine attitudes of subjects about AIDS and homosexuals. Preclinical medical students in London were used as subjects because they may be regarded as a surrogate for "the educated layman" in that they have a good knowledge of biological principles and are likely to have a high awareness of and interest in issues about AIDS without any specific clinical training in the disease. If factual information from a recent British government advertising campaign could be effective in modifying attitudes, it should be evident in this group. 1) Information/Education: Public Awareness (VA) 5A1-Mor-3 Author(s): Title: Source: Institution: Findings: Method: DiClemente, Ralph J., PhD; Zorn, Jim, BA; Temoshok, Lydia, PhD. Adolescents and AIDS: A Survey of Knowledge, Attitudes and Beliefs about AIDS in San Francisco. American Journal of Public Health, 1986, Vol. 76, No. 12: 1443-1445. Department of Psychiatry, School of Medicine, University of California, Langley Porter Psychiatric Institute, San Francisco, California. This study reports a survey of the knowledge, attitudes, and beliefs about AIDS among adolescents in San Francisco. With respect to disease transmission, 92% of the students correctly indicated that sexual intercourse was one mode of contracting AIDS; however, only 60% were aware that using a condom during sexual intercourse may lower the risk of getting the disease. This large discrepancy suggests that many adolescents, even while knowing that it is a major route of disease transmission, nonetheless will be engaging in unprotected sexual activity unless they abstain from intimate sexual contact. Most adolescents were aware that receiving infected blood from a transfusion (85%) or sharing intravenous drug needles (81%) are also routes of disease transmission. On the other hand, fewer of the students were aware that AIDS could not be spread by using someone's personal belongings (66%) or by engaging in casual contact such as shaking hands (68%). Less than half (41%) correctly reported that kissing was not a route of AIDS transmission. Adolescents were less informed about the treatment of AIDS. Surprisingly, only 25.3% and 36.8%, respectively, were aware that no new vaccine was available for treating AIDS and that AIDS could not be cured if treated early, respectively, and only 60.5% reported knowing that AIDS could not be cured. With respect to adolescents' attitudes and beliefs about AIDS, 78.7% reported being afraid of getting AIDS and 73.7% reported being worried about contracting the disease. One attitude that was the most pervasive (87.6% agreeing) was that it is important for Students to receive AIDS instruction in the school curriculum. The authors stress the need to develop and implement school health education programs on AIDS and other sexually transmitted diseases for adolescents, to curtail the spread of disease in this population. A self-report questionnaire was administered and completed anonymous- ly. The questionnaires consisted of 30 questions evaluating the students’ knowledge about the cause, transmission, and treatment of AIDS and 11 questions about students' attitudes and beliefs regarding personal susceptibility, disease severity, and the need for AIDS instruction to be included in high school curricula. Responses included true, false, and don't know. Questionnaires were distributed and returned within a I- 5A1-DiC~4 Sample Size: Policy Keys: week period in May 1985. More than 99% of the questionnaires distributed were returned and usable. Students enrolled in Family Life Education classes at 10 high schools in the San Francisco Unified School District were eligible to participate. Family Life Education classes are mandatory in this district. A total of 1,326 questionnaires represent the sample on which all analyses are based. Students ranged in age from 14 to 18 years and represented all major ethnic groups. 1) Information/Education: Public Awareness (VAL) V. Risk Reduction A. Information/Education 2. Risk Behaviors and Protection Author(s): Title: Source: Institution: Findings: Emmons, Carol-Ann, PhD; Joseph, Jill G., PhD; Kessler, Ronald C., PhD; Wortman, Camille B., PhD; Montgomery, Susanne B., MS; Ostrow, David G., MD. Psychosocial Predictors of Reported Behavior Change in Homosexual Men at Risk for AIDS. v Health Education Quarterly, Winter 1986, Vol. 13, No. 4: 331-345. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan. This study examined the relationship between psychosocial factors and the behavioral responses of homosexual men to the threat of AIDS. The core concepts measured by questionnaire were knowledge about AIDS, perceived risk, perceived efficacy of behavioral change, barriers to behavioral change (such as difficulties with sexual impulse control and belief that biomedical technology can prevent or cure AIDS), and social network characteristics (such as perceived social norms supporting behavioral change and gay social network affiliation). Knowledge about AIDS was generally high in the study group, with respondents scoring a mean of 4.8 on a scale of | to 7. Variation in knowledge about AIDS was the factor most strongly associated with the behavioral changes considered in this study. When asked about their absolute risk of developing AIDS, only 10% of the sample thought they had a large or very large chance of getting AIDS, 50% thought they had some chance, and the remaining 40% thought their chances of getting AIDS were small to negligible. There was a modest relationship of perceived risk to the global measure of any behavioral change and to attempts to reduce the number of sexual partners. At the same time, those who perceived themselves at higher risk were more likely to have anonymous sexual partners. However, since respondents with anonymous sexual partners may realize their increased risk, the influence between these two variables is bidirectional. Respondents in this cohort were generally very certain that behavior changes can reduce risk of AIDS; the mean score was 4.1 on a scale of 1 to 5. Few men reported difficulties of sexual impulse control, and those who did report such difficulties were less likely to have avoided anonymous partners. The belief that biomedical technology will be able to prevent or cure AIDS in the near future was associated with fewer attempts to reduce the number of sexual partners. There was no significant relationship between the measure of gay social network affiliations and any behavioral changes. Social norms supportive of behavior change, however (regardless of affiliation in gay networks), were significantly related to attempts to reduce the number of sexual partners. In all but those who believed themselves to be at highest risk, higher levels of perceived efficacy of behavior change were associated with desirable changes in behavior. The authors conclude that education emerges as the most important predictor of behavioral change, suggesting that increased educational efforts would result in the greatest improvement in behavior. 5A2-Emm-1 Method: Sample Size: Policy Keys: Participants were given self-administered questionnaires designed to assess a broad range of psychosocial variables thought to be related to homosexual men's responses to the threat of AIDS. The sample consisted of 909 of the 978 homosexual men participating in the Multicenter AIDS Cohort Study (MACS) in Chicago. Subjects were predominantly white (91.1%), with a mean age of 34.6 years and an average of 16.2 years of education and 16.5 years of homosexual experience. Enrollment took place from June 1984 to August 1985. The 909 participants included those men not diagnosed with AIDS, not being paid for sex, and for whom data were missing on no more than three items. 1) Information/Education: Risk Behaviors and Protection (VA2), 2) Populations: Homosexuals (IA1) Author(s): Title: Source: Institution: Findings: Friedman, Samuel R., PhD; Des Jarlais, Don C., PhD; Sotheran, Jo L., MA. AIDS Health Education for Intravenous Drug Users. Health Education Quarterly, Winter 1986, Vol. 13, No. 4: 383-393. Narcotic and Drug Research, Inc., New York, New York; New York State Division of Substance Abuse Services, New York, New York. Intravenous ([.V.) drug users are the second largest risk group for AIDS and the main link to infection of heterosexual partners and children. This article discusses methods of encouraging risk reduction in this group, as well as the factors which inhibit these efforts. [.V. drug users have an addiction and a subculture that make risk reduction difficult. For example, to refuse to share needles can endanger personal relationships, and keeping clean injection equipment (rather than renting it in a "shooting gallery") carries the risk of arrest. The risk of death was part of the drug subculture long before AIDS appeared; this tends to reduce the deterrent effect of the threat which AIDS represents. [.V. drug users have a deep mistrust of the outside world, as well as of other [.V. drug users. Communication is oral rather than written or printed, because written documents could be incriminating and many LV. drug users have difficulty reading and writing. There is evidence that I[.V. drug users in New York City have considerable knowledge about AIDS, and many have taken steps to protect themselves against the disease. In the summer of 1984, interviews with 59 patients in a Manhattan methadone maintenance program established that all of the patients knew of AIDS and 93% knew that [.V. drug use was a way to get the disease. Other evidence shows, however, that false beliefs may also be widespread, such as that you can get AIDS by drinking from the same cup as an infected person. Most (59%) of the I.V. drug users interviewed reported having made behavioral changes to avoid AIDS: 31% used clean needles more often or cleaned their needles more often, and 29% had reduced needle sharing; 51% reported that their friends had also changed their behavior. In addition, 48% had attempted to use safer sex practices by decreasing their number of sex partners, using condoms, or taking other hygienic measures. In another study, 314 methadone maintenance and drug detoxification patients were interviewed and, approximately 9 months later, 119 patients from this program were reinterviewed. Their reported drug injection frequencies dropped significantly from an average of 16 times per month in the 2 years prior to the first interview to 6 injections per month during the period between interviews; 25 subjects quit injection totally. Ethnographic studies indicate that the illicit market in New York City for sterile needles has increased greatly since the AIDS epidemic began. Almost 80% of [.V. drug users report that their primary sexual relation- ships were with women who did not themselves inject drugs. [.V. drug users also have considerable numbers of children. Patients in a methadone maintenance program had an average of almost two children 5A2-Fri-2 Method: Sample Size: Policy Keys: each, and a quarter of the patients indicated that they expected to have additional children. To encourage behavior change among [.V. drug users requires going beyond simple education; it entails trying to change the drug subculture. Outside intervention requires repeated messages from multiple sources, especially from organizations within the subculture; face-to-face, interactive communication; and perhaps the use of exaddicts as health educators. This article discusses methods of promoting risk reduction among I.V. drug users and their sexual contacts. Results are reported from survey interviews of patients in a methadone maintenance and drug detoxification program in Manhattan conducted in 1984 and 1985. Fifty-nine patients in a Manhattan methadone maintenance program were interviewed in summer 1984. Interviews were also conducted of 314 patients in a methadone maintenance or drug detoxification program in 1984, with follow-up of 119 patients in 1985. 1) Information/Education: Risk Behaviors and Protection (VA2), 2) Populations: [.V. Drug Abusers (IA2) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Martin, John L., PhD, MPH. AIDS Risk Reduction Recommendations and Sexual Behavior Patterns Among Gay Men: A Multifactorial Categorical Approach to Assessing Change. Health Education Quarterly, Winter 1986, Vol. 13, No. 4: 347-358. Columbia University, School of Public Health, New York, New York. As part of a longitudinal effort to determine the behavioral impact of the AIDS epidemic on the healthy but at-risk community, a sample of 745 New York City gay men were interviewed in 1985. Detailed sexual behavior histories were taken for the year before the interview (1984-85) and the year before the date that respondents first heard about AIDS (for this sample, the mode date was July 1981). The number of subjects engaging in all three high-risk behaviors--multiple sexual partners, sexual contact outside a private home, and high-risk sexual acts--decreased from 71% to 45% after learning of AIDS. For the sample as a whole, 40% changed at least one aspect of their behavior in the direction of reduced risk; however, 11% changed at least one aspect in the direction of increased risk. The most frequent changes were eliminating sex outside the home (31%) and engaging only in low-risk sexual activities (29%), but only 15% who had had multiple partners before learning about AIDS became monogamous or celibate. The categorical measures used focused on the presence or absence of a behavior and did not measure variations in quantity or frequency. In other words, a person reducing his number of partners from 20 to 2 is still classified as having multiple partners. The authors conclude that the message that risk reduction efforts are required by gay men has clearly gotten through to many people. However, personal approaches to risk reduction are varied, as the results indicate, and it is unlikely that each of these approaches is equally effective. The possibility that a segment of the gay community may be moving over time toward increased risk rather than decreased risk underscores the need for educational messages about the continued need for risk reduction in sexual behavior. The complexity of safe-sex behavior is important and central to education efforts aimed at homosexual as well as heterosexual audiences. All subjects were interviewed to obtain detailed sexual behavior histories for the year before the interview (1984-85) and the year before the date that respondents first heard about AIDS (mode, July 1981). An index of sexual behavior used was constructed from three factors: (1) the number of different sexual partners reported (none, one, or more); (2) sexual contact outside a private home (yes or no); and (3) specific high-risk sexual acts (yes or no). A total of 745 gay men from New York City, aged 20 to 65, made up the present sample. None was diagnosed as having AIDS. An initial pool of 291 men was recruited through gay organizations, volunteers, pilot sample referrals, the 1985 Gay Pride Festival, and a public health 5A2-Mar-3 clinic. The remainder were recruited through personal referrals by those already interviewed. All interviews were conducted between June and October 1985. Policy Keys: 1) Information/Education: Risk Behaviors and Protection (VA2), 2) Populations: Homosexuals (IA 1) Author(s): Titles Source: Institution: Findings: Siegel, Karolynn, PhD; Grodsky, Phyllis B., PhD; Herman, Alan, PhD. AIDS Risk-Reduction Guidelines: A Review and Analysis. Journal of Community Health, Winter 1986, Vol. 11, No. 4: 233-243. Department of Social Work, Memorial Sloan-Kettering Cancer Center (Siegel, Grodsky); Department of Public Health, Cornell University Medical College; Department of Health Education, Borough of Manhattan Community College of the City University of New York, New York, New York (Herman). Safe-sex and risk reduction brochures and pamphlets have emerged as the principal means of effecting behavior changes among homosexual and bisexual men at risk for AIDS. This study describes the characteristics of 22 brochures, focusing on their common features, and examines the extent to which the brochures incorporate the elements of a standard model of health communication. A descriptive analysis of the content and style of the 22 pamphlets revealed that 19 provided very specific information about what practices should be avoided, 16 were likely to invoke some sense of threat in the reader, 16 used the vernacular of the gay subculture, 14 restricted the focus of the recommendations to AIDS without generalizing them to other sexually transmitted diseases, 4 advised readers to discuss sexual limits with prospective partners, 11 encouraged readers to feel responsible for other members of the gay community in their sexual behavior, 11 provided information on the symptoms associated with AIDS, 10 were directive in their language, 9 explained why particular sexual practices are risky, 8 offered some ranking of the relative risks associated with different practices, 7 advised readers to examine their partners' bodies for any evidence of disease before engaging in sexual relations, 7 affirmed the importance of sexual expression, and & indicated what behaviors to avoid rather than giving suggestions for safe- sex behaviors. A second objective of this study was to assess whether the brochures contained the components of a standard model of health communications, in this case the dual-process model. Consistent with this model, most of the brochures provided sufficient information on how AIDS is trans- mitted. In addition, over two-thirds of the brochures purportedly appropriately used emotionally laden terms or phrases to motivate change. However, none of the brochures outlined a scheme or strategies that could be adopted to deal with the threat, although one-third offered concrete suggestions that might be one element of such a plan. Reassurances that the reader is capable of accomplishing such difficult changes and that these changes can be part of a constructive, positive lifestyle occurred in only a small minority of pamphlets. Recommendations were also sometimes ambiguously worded, which may inadvertantly undermine their objective. The authors conclude that most available brochures on risk reduction or safe sex that have been developed to help limit the spread of AIDS fail to exploit important opportunities to educate and motivate their readers. 5A2-Sie-4 Method: Sample Size: Policy Keys: These materials may be the only public health intervention that will reach the overwhelming majority of homosexual and bisexual men. The task of these brochures, especially in locales such as New York and San Francisco, where knowledge of AIDS is high, must be to increase motivation to modify risky sexual behavior. Content analysis was used to evaluate brochures on AIDS safe-sex practices and risk reduction. Each brochure was carefully reviewed with the goal of discerning a set of categories that could be used to characterize content and style. A total of 13 categories were established, each measured as being present or absent. Each brochure was also evaluated for whether it contained the components of a standard model of health communication, the dual-process model. The principal elements of the dual-process model are a message that elicits fear and attracts attention to the threat, so that emotion is associated with the disease and its consequences, but not with its diagnosis and treatment; information about the causes and consequences of the threat and the likelihood of benefits from action; an action plan outlining steps or strategies for dealing with the threat; and information to reassure the individual that he or she is capable of successfully coping with the threat. A sample of 22 safe-sex brochures were gathered from public and private health organizations throughout the United States. They came from a number of different cities, including those with the highest incidence of AIDS (e.g., New York and San Francisco) as well as from cities with lower rates (e.g., Philadelphia, Denver, and Chicago). They were produced by government agencies (e.g., The Ohio Department of Health), gay organizations (e.g., the Gay Men's Health Crisis Center, New York City), and health care providers (e.g., Bay Area Physicians for Human Rights). The total number of such brochures in existence is not known, but the investigators judge this sample to be representative. 1) Information/Education: Risk Behaviors and Protection, Public Awareness (VA2,1), 2) Populations: Homosexuals (IA1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Feldman, Douglas A., PhD. AIDS and Social Change. Human Organization, Winter 1985, Vol. 44, No. 4: 343-348, Department of Degree Studies, New York University, New York, New York. This pilot study was conducted to measure concern about AIDS and to ascertain the pattern of social change as a response to the AIDS epidemic within the gay male community of New York. Respondents reported a decrease in sexual contacts, from an average of 6.8 different partners a month prior to hearing about AIDS to an average of 3.6 (about half as many) partners after hearing about the disease. Forms of sexual behavior also underwent significant changes, although about half (49.6%) of sample respondents said they had not changed their sexual behavior since they first heard about AIDS. Of those who had changed their behavior, they were more likely to have reduced active and passive oral sex, active and passive anal sex, and tongue kissing. They were more likely to have completely stopped oral-anal contact, "fisting," and swallowing semen and were more likely to have increased masturbation and mutual masturbation. Most (61.0%) of the respondents said that they were familiar with the symptoms of AIDS; however, 39.0% reported that they were not familiar with the symptoms. Respondents in their 30s were more likely to be familiar with the symptoms than younger respondents; black Americans and Hispanic Americans were least familiar, while Irish Americans and Jewish Americans were most familiar. Poorer respondents and those who were less educated also reported less familiarity. Study findings indicate the importance of understanding patterns of social interaction, the social structure and organization, and the shared values and ideology of the gay milieu in facilitating AIDS health education programs and documenting cultural patterns in affected high-risk populations. A two-page questionnaire was designed and, after pretesting, was distributed to homosexual and bisexual men in New York City at a wide variety of gay organizations, churches, bars, baths, professional and medical services, and at the corner of Hudson and Christopher Streets (a major crossroad within the gay community in New York City). Questionnaire items included the respondent's demographic charac- teristics (age, income, educational level, sexual orientation, type of homosexual organization, and ethnic group) and questions concerning number of partners, sexual behavior, and familiarity with AIDS symptoms. Approximately 1,600 questionnaires were distributed, and 403 were returned. The questionnaire was self-administered. Respondents were compared for two time periods: August 1982 to mid-February 1983 and mid-February 1983 to August 1983. A sample of 403 male homosexual subjects in New York City responded to the study questionnaire. The author states that the sample, while it is 5A2-Fel-5 not random, appears to be a diversified composite of the male homosexual population in New York. Policy Keys: 1) Information/Education: Risk Behaviors and Protection, Public Awareness (VA2,1), 2) Related Policy Issues: Community Responses (VIC) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services. Self-Reported Behavioral Change Among Gay and Bisexual Men--San Francisco. Morbidity and Mortality Weekly Report, 11 October 1985, Vol. 34, No. 40: 613-615. Centers for Disease Control, Atlanta, Georgia. A telephone survey was conducted to assess the extent to which gay and bisexual men in San Francisco have changed their sexual behavior. From August 1984 to April 1985, the proportion of 301 gay and bisexual men who reported that they were monogamous or celibate or performed "unsafe" sexual practices only with their steady partner increased from 69% to 81%. Similarly, fewer respondents reported having more than one sexual partner in the past 30 days at the second survey date (36% versus 49%). The proportion who reported intercourse without a condom with a secondary partner in the last 30 days decreased from 18% to 12%. Only 7% reported having anal sex with exchange of semen with a secondary partner in the past 30 days, down from 17%. In August 1984 and April 1985, surveys of risk factors for human T-cell lymphotropic virus type IllI/lymphadenopathy-associated virus (HTLV- IlI/LAV) infections in gay and bisexual men living in San Francisco, California, were conducted. The surveys used a random probability sample designed to provide information about the sexual practices of these men. The sample was drawn from telephone numbers listed with only male names. City census tracts were weighted according to the proportion of unmarried males residing in each area. Exceptional care was taken to identify appropriate respondents. Following a brief introduction about the survey and an assurance of confidentiality, potential respondents were asked whether they had sex with other men or identified themselves as gay or bisexual. Those who responded positively were considered eligible and asked to participate. A total of 500 men were interviewed in the August 1984 survey. In April 1985, participants from the original panel of 500 were selected randomly and telephoned. Of those contacted, 93.2% agreed to participate again, for a total of 301 repeat interviews. 1) Information/Education: Risk Behaviors and Protection (VA2), 2) Populations: Homosexuals (IA 1), 3) Transmission: Sexual Activity (IIA) 5A2-Cen-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: McKusick, Leon, MS; Horstman, William PhD; Coates, Thomas J., PhD. AIDS and Sexual Behavior Reported by Gay Men in San Francisco. American Journal of Public Health, May 1985, Vol. 75, No. 5: 493-496. AIDS Behavioral Research Project, University of California, San Francisco. This study was motivated by two concerns: to determine whether gay men's sexual behavior had changed since the appearance of AIDS in response to the crisis, and to understand better the factors influencing sexual behavior so that future health education programs could be designed accordingly. Bathhouse frequenters showed little change over 1 year in frequency of bathhouse use and in number of bathhouse sex partners. Three other groups showed substantial reduction in frequency of sexual contacts from bars, bathhouses, T-rooms (bathrooms), and parks. Men in monogamous relationships showed little change in sexual behavior within that relationship. Men in nonmonogamous relationships and men not in relationships reported substantial reductions in high-risk sexual activity but no corresponding increase in low-risk sexual behavior. Knowledge of health guidelines was generally quite high, but this knowledge had no relation to sexual behavior. Using sex to release tension and to express gay identity and knowledge of persons with AIDS in its advanced stages were all related to frequency and type of sexual behavior. Of the bathhouse group, 50% still believed, as did 58% of the bar group, that they were less susceptible to AIDS than were others. Sexual behavior may be comparable to other high-risk behaviors--tobacco smoking, obesity, not using seat belts, and alcohol consumption--in that knowledge alone is not sufficient to change behavior. Survey questionnaires were distributed to the four study groups (two high-risk groups and two low-risk groups); the 309 questions covered demographic data, health history, current attitudes toward sex with multiple partners, and awareness of AIDS and safe sex practices. Reports of frequency of specific sexual activities inside and outside relationships were solicited for the previous month and the same month a year earlier. Sex practices were designated high-risk (active oral-anal, receptive anal-manual contact ("fisting"), drinking urine, unprotected receptive anal intercourse, and swallowing semen) and health-conscious (receptive anal intercourse with condom, receptive coitus interruptus, mutual masturbation). A total of 655 homosexual men in San Francisco returned survey questionnaires (42% of those distributed): 285 of these were selected to be at high risk for AIDS (151 frequenters of bathhouses and 134 frequenters of gay bars), while 370 were selected to be at low risk for AIDS (189 who did not frequent bathhouses or bars for sexual contacts and 181 committed to a monogamous relationship). 1) Information/Education: Risk Behaviors and Protection (VA2), 2) Populations: Homosexuals (IAl), 3) Transmission: High-Risk Sexual Behavior (IIA). 5A2-McK-7 V. Risk Reduction B. Blood Product Safety l. Screening Tests and Assays Author(s): Title: Source: Institution: Findings: Method: Sample Size: Reesink, Henk W.; Huisman, J.G.; Gonsalves, M.; Winkel, I.N.; Hekker, A.C.; Lelie, P.N.; Schaasberg, W.; Aaij, C.; Van der Does, J.A.; Desmyter, J.; Goudsmit, J. Evaluation of Six Enzyme Immunoassays for Antibody against Human Immunodeficiency Virus. The Lancet, 30 August 1986, Vol. 2, No. 8505: 483-4386. Red Cross Blood Bank, Amsterdam, The Netherlands (Reesink); Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (Huisman, Gonsalves, Winkel, Lelie, Schaasberg, Aaij); Red Cross Blood Bank, The Hague, The Netherlands (Van der Does); National Institute for Public Health, Bilthoven, The Netherlands (Hekker); Rega Institute, University of Leuven, Belgium (Desmyter); Department of Virology, University of Amsterdam, The Netherlands (Goudsmit). Six commercial enzyme immunoassays (EIAs) were evaluated with 6,488 serum samples, with immunoblot analysis as the confirmatory test for antibodies against human immunodeficiency virus (HIV). The six EIAs were sensitive enough to detect 98% to 100% of the HIV antibody- positive serum samples. The Abbott and Wellcome tests correctly identified all 163 immunoblot-confirmed positive samples, whereas the other tests did not detect from | to 3 positive samples. No EIA was as sensitive as the immunoblot technique in symptom-free subjects positive for HIV antibody, as judged from diluted samples. Significantly more false-positive results were found in the Abbott and Litton tests than the Organon, Wellcome, and Pasteur tests. The predictive value of a positive test result in the panel of blood donors was only 5% for Abbott and Litton and 25 to 100% for the other EIAs. A panel of tricky samples which might be likely to cause false-positive results included samples from patients with acute viral diseases, samples positive for HLA-DR4, and samples from patients with autoimmune diseases, from cancer patients, and from some healthy individuals. The Wellcome and Pasteur tests scored no false-positives on this panel, but significant numbers of false-positives were found in tests by Abbott, Behring, and Organon. In general, the six EIAs evaluated are of good quality, and the risk of posttransfusion AIDS is probably very low. The assays evaluated were from Abbott, Organon, Litton Bionetics, Behring, Wellcome, and Pasteur. All serum samples were tested with each assay, and any samples that were repeatedly reactive in any EIA were confirmed by the immunoblot technique. All samples in panel A (AIDS and AIDS-related compled [ARC] patients) and panel C (diluted samples from AIDS patients and symptom-free subjects positive for HIV antibody) were tested by immunoblot regardless of the EIA results. Samples were divided into five panels: (A) samples from 57 Dutch AIDS patients, 6 African AIDS patients, and 8 Dutch ARC patients; (B) samples from high-risk groups--148 male homosexuals, 101 hemophiliacs, 50 intravenous drug abusers, and 25 carriers of hepatitis B virus surface antigen; (C) dilutions of 20 samples from AIDS patients and of 20 samples from symptom-free subjects positive for HIV antibody; (D) tricky panel-- 87 samples from patients with acute viral diseases (cytomegalovirus, 5B1-Ree-1 Policy Keys: Epstein-Barr virus, hepatitis virus A or B), 6 samples positive for HLA- DR4, 100 from patients with autoimmune diseases, 50 from cancer patients, and 50 from healthy Dutch individuals; and (E) 5,000 samples from blood donors at the Amsterdam Red Cross Blood Bank collected at the beginning of 1984. 1) Blood Product Safety: Screening Tests and Assays (VB1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Barrett, Jean E., MS; Dawson, George, PhD; Heller, John, PhD; Bairstow, Carolyn, BS; Fico, Rosario, PhD; Webber, J. Scott, BS; Gutierrez, Robin, BS; Decker, Richard H., PhD. Performance Evaluation of the Abbott HTLV-III EIA, a Test for Antibody to HTLV-III in Donor Blood. American Journal of Clinical Pathology, August 1986, Vol. 86, No. 2: 180-185. Abbott Diagnostics, Abbott Laboratories, North Chicago, Illinois. This evaluation was conducted to assess the sensitivity and specificity of the Abbott Laboratories enzyme immunoassay (EIA) designed to detect antibodies to human T-cell lymphotropic virus type [II (HTLV-II). The EIA was found to be highly sensitive, detecting antibodies to HTLV-III in 221 of 223 (99.1%) patients with AIDS. For comparison, 133 of 140 (95%) lymphadenopathy syndrome (LAS) specimens were positive. The antibody test was also found to be highly specific, identifying 20,668 of 20,720 (99.75%) serum or plasma samples from normal blood donors as negative for antibody to HTLV-II. Confirmation by Western blot analysis revealed that 81 of 82 (98.8%) EIA-positive samples from patients with AIDS were Western blot positive; of EIA-positive normal blood donors, 21 of 36 (58%) were detected and confirmed by the Western blot technique. A competitive EIA was also evaluated, and it showed a sensitivity approximately equivalent to that of the Western blot technique. Preliminary results reported in this study indicate that this immunoassay is highly sensitive and highly specific in screening for antibody to HTLV- III. Abbott's HTLV-II EIA, a competitor's EIA, and the Western blot technique were used to test for antibody to HTLV-III. Clinical evaluation of sera obtained from patients with AIDS, patients with LAS, and normal blood donors was performed at 10 laboratories in eight geographic locations throughout North America, including Abbott Laboratories, commercial blood banks, and university medical centers. Donor blood specimens were randomly distributed over these locations, while specimens from patients with AIDS-related complex (ARC) and other disorders were obtained and tested primarily at the two university medical centers. Specimens from donors and patients in high-risk groups were tested by single determinations with three different lots of reagents supplied by Abbott. All reactive and borderline specimens (within 10% of the cutoff) were repeated (in duplicate), and repeatedly reactive samples were sent to Abbott for further evaluation by various confirmation procedures. The study analyzed sensitivity (ability to detect antibody), with 223 specimens from patients with clinically diagnosed AIDS and 140 specimens from patients with LAS. The specificity of the test (ability to detect antibody-negative samples) was calculated after analysis of 5B1-Bar-2 20,720 serum and plasma samples from normal blood donors; 14,965 specimens were tested at eight clinical sites, and 5,755 specimens were tested at Abbott Laboratories. Policy Keys: 1) Blood Product Safety: Screening Tests and Assays (VBI) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Abb, J. Evaluation of a New Confirmatory Assay for Antibodies against Lymphadenopathy-Associated Virus (LAV)/Human T-Lymphotropic Virus Type III (HTLV-II). Vox Sanguinis, 1986, Vol. 51: 233-235. Bavarian Red Cross Blood Transfusion Services, Institute Nurnberg, Federal Republic of Germany. Commercial enzyme immunoassay (EIA) testing kits, devised primarily for screening blood donations, have emphasized sensitivity but may produce false-positive results and require confirmatory testing by other, more sophisticated systems. This study reports preliminary findings in the evaluation of a newly developed EIA to detect antibodies to lymph- adenopathy-associated virus/human T-cell lymphotropic virus type III (LAV/HTLV-III), comparing its performance against conventional methods of confirmatory testing. The EIA evaluated for this study focuses on selected antibodies and allows improved specificity in detecting antibody to LAV/HTLV-III. Study results also indicate that the sensitivity of the confirmatory EIA may be higher than that of the immunoblot and immunofluorescence methods currently recommended as confirmatory tests. The author suggests that ease of handling, enhanced specificity, and improved sensitivity should make this confirmatory EIA a useful tool in screening donor blood for the presence of antibody to LAV/HTLV-IIL Sera were screened with a commercial EIA for LAV/HTLV-III antibody (Abbott Laboratories). Sera repeatedly reactive in the screening test were analyzed by immunofluorescence and immunoblot techniques, both widely accepted as confirmatory tests. Further evaluation was done with a competitive EIA for the detection of antibodies against LAV/HTLV-III envelope and core proteins (Abbott Laboratories). Sera were obtained from high-risk donors (male homosexuals, patients with hemophilia, and intravenous drug abusers) and from voluntary blood donors. 1) Blood Product Safety: Screening Tests and Assays (VBI) 5B1-Abb-3 Author(s): Title: Source: Institution: Findings: Method: Fang, C.T.; Darr, F.; Kleinman, S.; Wehling, R.H.; Dodd, R.Y. Relative Specificity of Enzyme-Linked Immunosorbent Assays for Antibodies to Human T-Cell Lymphotropic Virus, Type III, and Their Relationship to Western Blotting. Transfusion, 1986, Vol. 26, No. 2: 208-209. American Red Cross Blood Services, Bethesda, MD, Washington, DC, Los Angeles, California; Aurora Area Blood Bank, Aurora, Illinois. This study compares the performance of licensed and developmental test kits for human T-cell lymphotropic virus type III (HTLV-II) antibody on the same donor samples in order to determine whether positive samples confirmed by Western blot could also be identified by the sequential use of enzyme-linked immunosorbent assay (ELISA) tests. The study also directly compared the ability of the ELISA tests to identify HTLV-II antibody-seropositive donors. Each of the four test kits showed repeatedly reactive results that could not be confirmed by Western blot. Of 73 samples tested, each of which were included because they had been found to be repeatedly reactive by one of three testing methods, 23 were found to be Western blot positive, 40 were negative, and 10 were nonreactive by any ELISA test and also Western blot negative. All 23 Western blot-positive samples were reactive in the Abbott, Electro-Nucleonics (ENI), and Genetic Systems Corp. (GSC) tests; only 18 were reactive in the Litton test. The 40 Western blot-positive samples were found to be reactive by at least one of the three licensed ELISA kits. Overall, 32 samples reacted in the Abbott test, 46 samples reacted in the Litton test, and 49 samples reacted in the commercial ENI test. Twenty- four of 26 samples were reactive by the licensed ENI test but negative by Western blot, and when tested by the unlicensed ENI ELISA test reacted with uninfected H9 cells (used to grow HTLV-II). However, all 23 Western blot-negative samples were interpreted as true positives on the basis of the same H9 cell ELISA procedure. The GSC test detected 24 reactive samples, including all 23 Western blot-positives in the population. False-positive results, identified as samples which were reactive by ELISA tests for HTLV-III antibody but negative by Western blot, appear to be attributable to reactivity with determinants of the H9 cells used to grow HTLV-II, supported by the finding that with lymphadenopathy-associated viral antigen derived from an alternate cell substrate (CEM), the test showed an absence of reactivity. Three commercially available licensed test kits were used, each of which is based on HTLV-III grown in HY cells. Test kits were purchased from Abbott Laboratories, North Chicago, Illinois; ENI, Columbia, Maryland; and Litton Bionetics (distributed under Organon Teknika), Charleston, South Carolina. A developmental test for antibodies to LAV grown in CEM cells was obtained from GSC, Seattle, Washington, and a 5B1-Fan-4 Sample Size: Policy Keys: developmental test for antibodies to the uninfected H9 cell substrate, provided by ENI, was also used in the study. The sample population of 73 donor samples included 39 samples repeatedly reactive by the Abbott test which were obtained from the American Red Cross Blood Services, Washington, D.C., Region; 22 samples repeatedly reactive by the Litton test which were obtained from the American Red Cross, Los Angeles-Orange County Region; and 12 samp es repeatedly reactive by the ENI test which were obtained from the Aurora Area Blood Bank, Aurora, Illinois. 1) Blood Product Safety: Screening Tests and Assays (VBL), 2) Popula- tions: Blood Donors (IA7) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Hedenskog, Mona; Dewhurst, Stephen; Ludvigsen, Carl; Sinangil, Faruk; Rodriguez, Luis; Wu, YinTang; Volsky, David J. Testing for Antibodies to AIDS-Associated Retrovirus (HTLV-III/LAV) by Indirect Fixed Cell Immunofluorescence: Specificity, Sensitivity, and Applications. Journal of Medical Virology, 1986, Vol. 19: 325-334. Molecular Biology Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska. Ideally, one serological test for antibody to human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) should suffice for all epidemiological and screening purposes, but easily automated tests, such as the enzyme-linked immunosorbent assay (ELISA), are still lacking in both sensitivity and specificity, whereas more reliable tests, such as Western blotting and radioimmunoprecipitation (RIP), are too laborious for use outside research laboratories. In this study, an alternate method, the indirect immunofluorescence assay (IFA), was compared with the ELISA for sensitivity and specificity. Specific and nonspecific patterns of immunofluorescence were easily distinguished. All of the IFA-positive sera tested by Western blotting or RIP were also positive by these confirmatory assays. A total of 84 sera were tested by both IFA and ELISA. Of these, 75 (89%) gave the same result by both assays. The seven ELISA-positive, IFA-negative sera were negative on Western blotting, while two ELISA-negative, IFA-positive sera were positive on Western blotting. These two samples were from an AIDS and an AIDS-related complex (ARC) patient with low levels of antibody, and virus was isolated from one on two separate occasions. Data also suggest that levels of antibody in serum rise as the disease progresses, ultimately falling as severe complications ensue. Sera were obtained from a variety of individuals on three continents. All sera were tested by IFA, ELISA, Western blotting, and RIP. Serum samples were obtained from four different locations: 330 from New York City, 139 from Nebraska, 1,115 from Venezuela, and 649 from Spain. The subjects from New York City included AIDS and ARC patients and asymptomatic homosexuals; those from Nebraska were healthy homosexuals and heterosexuals and hemophiliacs; those from Venezuela were healthy people from urban and rural areas, aboriginal Indians, hemophiliacs, and patients with malaria, leukemia, Chagas’ disease, and filaria; and Spanish subjects included drug abusers, blood donors, alcoholics, and health care workers. 1) Blood Product Safety: Screening Tests and Assays (VBl), 2) Immunological Aspects (IIIE) 5B1-Hed-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kuhnl, P.; Seid), S.; Holzberger, G. Anti-HTLV-III Screening of Blood Donors. Vox Sanguinis, 1986, Vol. 51, Suppl. 1: 15-20. Institute of Immunohematology, University of Frankfurt; Red Cross Blood Transfusion Service Hessen, Frankfurt, Federal Republic of Germany. In a survey of 82,383 blood donor specimens in Hessen, West Germany, two commercially available enzyme-linked immunosorbent assays (ELISAs) for human T-cell lymphotropic virus type III (HTLV-II) antibodies were tested. In the Abbott ELISA, 146 of 48,652 (0.3%) samples were repeatedly positive, but only 7 of them were positive in at least two confirmatory tests: Western blot (WB), indirect immunofluor- escence (IFA), and radioimmunoprecipitation (RIPA). In the Organon Teknika series, 18 of 33,731 (0.05%) were repeatedly ELISA positive, and 8 of these were confirmed. This suggests a high degree of nonspecific false-positive results on the ELISA tests, especially for the Abbott ELISA. One of the causes for false-positives is HLA-DR#4 (a specific tissue transplantation compatibility antigen) antibodies, which react wth DR4 antigen reportedly contaminating the cells used in the HTLV-II test. Among 1,153 prison inmates who were also tested, 9 (0.78%) were found clearly positive in the Organon Teknika ELISA and also in WB and IFA. All nine had a history of drug abuse. This cannot be considered a conclusive positivity rate for this population, however, because those tested were volunteers, not a random sample. Only 1 of 127 patients on chronic hemodialysis was found to be repeatedly weakly positive in the Abbott ELISA but negative in all confirmatory tests. The most likely explanation for his positivity was HLA-DR?7 antibodies cross-reacting with DR4. Two commercially available (Abbot and Organon Teknika) ELISAs were used as primary screening procedures for HTLV-II antibodies in donor blood specimens. Initially positive blood samples were retested twice by ELISA, marked not to be used for transfusion, and subjected to three additional confirmatory tests: IFA, WB, and RIPA. Between April and October 1985, 82,353 blood donor specimens were tested. In addition, 1,153 prison inmates and 127 patients undergoing chronic hemodialysis were also tested in September 1985 and March 1985 respectively. All groups were from Hessen, Federal Republic of Germany. 1) Blood Product Safety: Screening Tests and Assays (VBL), 2) Geographic Trends: Europe (West Germany) (IB4), 3) Populations: Prison Inmates (IA7), 4) Populations: Hemodialysis Patients (IA7) 5B1-Kuh-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Parry, John V. An Immunoglobulin G Capture Assay (GACRIA) for Anti-HTLV-III/LAV and Its Use as a Confirmatory Test. Journal of Medical Virology, 1986, Vol. 19: 387-397. PHLS Virus Reference Laboratory, Central Public Health Laboratory, London, England. It is generally accepted that positive and unexpected negative results of enzyme-linked immunosorbent assay (ELISA) tests for antibody to human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) need to be confirmed, but to do this adequately several different methods must be applied. An immunoglobulin G antibody capture radioimmunoassay (GACRIA), which is a solid-phase assay methodologically distinct from other confirmatory tests, was developed and compared with a competitive radioimmunoassay (COMPRIA) in screening serum samples for HTLV-III/LAV antibody. On initial testing of 1,055 serum samples, 823 (78%) were positive and 129 (12.2%) were negative by both assays, while 103 gave conflicting results. The GACRIA results were more reproducible than the COMPRIA results: on repeat testing of the 103 discrepancies, 77 COMPRIA results changed, while only 4 GACRIA results changed. The 22 samples that gave rise to persistently discordant results were of four sorts: two samples were of pooled sera so that the product was only weakly reactive; five samples were only weakly reactive in COMPRIA; five were GACRIA negative but significantly reactive in a similar test, an immunoglobulin M capture assay (MACRIA); and ten sera were from a single laboratory where improper techniques may have led to cross-contamination of samples. The GACRIA is very specific, giving rise to only one false-positive result over 8 months of routine practice involving approximately 4,000 samples that required confirmatory testing. In particular, samples of sera collected from patients with infectious mononucleosis or containing HLA-DR#4 or other autoantibodies which are prone to cross-reaction in various commercial ELISAs, did not give rise to false-positive reactions in GACRIA. Because GACRIA is a specific and fairly sensitive assay for HTLV-III antibody, the authors conclude that it is particularly suitable as a confirmatory test. They also point out that GACRIA could be readily developed as an ELISA. All serum samples were tested by both COMPRIA and GACRIA. If the results from the two assays were discordant for any sample, the sample was also retested by GACRIA. Samples that continued to differ were tested by a third assay; some were also retested by Western blot. To set an appropriate cutoff value for the GACRIA, 220 unselected blood donors were tested. In addition, 1,055 other serum samples from individuals considered to be at risk were tested. They were selected for testing by GACRIA if (1) they gave rise to positive or equivocal results by COMPRIA, (2) they gave rise to a negative result that was unexpected on clinical grounds, or (3) they were referred for confirmatory testing from elsewhere. 5Bl1-Par-7 Policy Keys: 1) Blood Product Safety: Screening Tests and Assays (VB1) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Peetoom, Frans, MD; Curry, Betty; Dodd, Roger, PhD; Fang, Chang T., MS; Goldstein, Lynn, MD; Perkins, Herbert, MD; Schneider, George, MD; Wandell, Mike, PhD. Use of an Enzyme Immunoassay for Detection of Antibody to Human Immunodeficiency Virus in Low Risk Populations. Transfusion, 1986, Vol. 26, No. 6: 536-538. Pacific NW Region, Portland, Oregon (Peetoom); Cutter Biological Special Testing Laboratory, San Diego, California (Curry); American Red Cross, Bethesda, Maryland (Dodd, Fang); Genetic Systems Corporation, Seattle, Washington (Goldstein, Wandell); Irwin Memorial Blood Center, San Francisco, California (Perkins); Spokane and Inland Empire Blood Bank, Spokane, Washington (Schneider). A new enzyme immunoassay (EIA) for detection of antibody to human immunodeficiency virus (HIV) was tested in clinical trials of 9,703 blood and plasma donations. Of the total, 34 (0.4%) were initially reactive and 21 (0.2%) were repeatedly reactive. Specificity, as defined by the Food and Drug Administration, is the percentage of blood and plasma donors found to be repeatedly reactive subtracted from 100%, based on the assumption that 100% of blood donors would have negative EIA results. In this study specificity was found to be 99.8%. Of the initially reactive samples, 62% (21 of 34) were repeatedly reactive. Only 14 of these 21 (67%) were found positive by a reference method, radioimmunoprecipita- tion (RIP). Therefore, using the RIP reference method, the EIA demonstrated 99.9% specificity, and the predictive value of a positive result was 67%. None of the 514 randomly selected samples that were EIA negative was positive by RIP. The authors suggest that the use of the EIA might reduce the number of blood units and blood donors rejected for being falsely positive. All specimens were tested by the LAV EIA (Genetic Systems Corpora- tion, Seattle, Washington) in five study centers according to the manufacturer's instructions. Positive specimens were retested to see whether they were repeatedly reactive. A subset of specimens was tested by the reference method, RIP. RIP assays were performed on all repeatedly reactive specimens and on a computer-selected random sample of 514 EIA-negative specimens (at least 100 from each site). Serum and plasma specimens were obtained from subjects from five geographically distributed testing sites, including one plasma and four blood-screening centers. A total of 6,593 voluntary blood donors and 3,110 paid plasma donors were tested. 1) Blood Product Safety: Screening Tests and Assays (VB1) 5B1-Pee-8 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Mortimer, P.P.; Parry, J.V.; Mortimer, J.Y. Which Anti-HTLV-III/LAV Assays for Screening and Confirmatory Testing? The Lancet, 19 October 1985, Vol. 2, No. 8460: 873-877. PHLS Virus Reference Laboratory; Central Public Health Laboratory; PHLS Communicable Disease Surveillance Centre, London, England. In preparation for routine human T-cell lymphotropic virus type II/lymphadenopathy-associated virus (HTLV-II[/LAV) antibody testing in the United Kingdom, five commercial assays were evaluated with 360 blood serum samples from blood donors and patients in high-risk groups and specimens with features likely to cause false-positive results. By interpretation of the combined results, all 220 blood donors and all 57 potentially false-positive specimens were assumed to be antibody negative. Of the 83 high-risk group specimens, 72 were assumed to be positive and 11 negative. False-positive or equivocal results arose for 17 negative specimens by assay A, 4 by B, and 1 by C. Most of these were from the potential false-positive group. After heat treatment, all assays except C performed differently, leading to high numbers of false- positives for assays A and B. Assay C gave rise to a false-positive result on a single specimen with strong anti-HLA-DR#4 and -B5 both before and after heat treatment. Aside from this one false-positive result by C, assays C, D, and E were highly specific and reproducible. C and E also discriminated most clearly between positive and negative sera. These two assays were rapid and convenient and seemed particularly suitable for testing blood donations. Assay D was comparable in performance but more difficult to use. Three categories of serum specimen -- blood donor, high-risk group, and potentially false-positive -- were assembled without knowledge of HTLV- III/LAV reactivity. Five commercial enzyme-linked immunosorbent assay (ELISA) kits for HTLV-III/LAV (designated A through E) were evaluated, and for comparison, a set of specimens was examined by a competitive radioimmunoassay and an immunoglobulin G capture assay developed in the Virus Reference Laboratory, Colindale. In assays A through E results were expressed as optical density values and related to a cutoff value. Values above the cutoff in assays A through D and below the cutoff in assay E indicated positivity. Blood donor samples were obtained from 220 successive donors at the North London Blood Transfusion Centre. Of the 83 high-risk subjects, 4 had AIDS, 37 had persistent generalized lymphadenopathy, 11 were contacts of AIDS or lymphadenopathy patients, and 31 were hemophiliacs. The remaining 57 samples were from patients whose sera might give rise to false-positive reactions because of other acute viral infections, antibodies to particular human leukocyte antigen types, or other reasons. 1) Blood Product Safety: Screening Tests and Assays (VBL), 2) Populations: Blood Donors (IA7), 3) Geographic Trends: Europe (U.K.) (IBY) 5B1-Mor-9 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Carlson, James R., PhD; Bryant, Martin L., MD, PhD; Hinrichs, Steven H., MD; Yamamoto, Janet K., PhD; Levy, Norman B., MD; Yee, JoAnn; Higgins, Joanne; Levine, Alexandra M., MD; Holland, Paul, MD; Gardner, Murray B., MD; Pedersen, Niels C., DVM, PhD. AIDS Serology Testing in Low- and High-Risk Groups. Journal of the American Medical Association, 21 June 1985, Vol. 253, No. 23: 3405-3408. Departments of Medical Pathology (Carlson, Bryant, Hinrichs, Yamamoto, Levy, Gardner, Lee) and Veterinary Medicine (Pedersen, Higgins), University of California, Davis, California; Department of Medicine, Kenneth Norris Jr. Cancer Center, University of Southern California, Los Angeles (Levine); Sacramento Medical Foundation Blood Center (Holland), Sacramento, California. Serum specimens from low- and high-risk groups for AIDS were tested to determine the performance characteristics of the enzyme-linked immunosorbent assay (ELISA) test by confirmatory testing by Western blot and immunofluorescence assay (IFA). Defining an ELISA positive/negative (P/N) ratio of >2 as positive, false-positive ELISA results occurred for 6 of 74 laboratory personnel, 91 of 1,014 unselected blood donors, | of 22 asymptomatic homosexual men, | of 45 hemophiliacs, and none of the AIDS-related complex (ARC) or AIDS patients, based on Western blot confirmation. Only two true-positives were detected among the laboratory personnel and unselected blood donors (low-risk groups). In contrast, 106 of 108 ELISA-positive specimens from high-risk groups (asymptomatic homosexual men, hemophiliacs, ARC patients, and AIDS patients) were also positive by Western blot and IFA. Four false-negative ELISA results, based on Western blot and IFA, were found among the AIDS patients. Ten of 69 AIDS patients were negative by all three serological tests. If a higher cutoff for the ELISA ratio were used, which would greatly increase the specificity of the test, sensitivity would be sacrificed, resulting in several false-negative results. Parallel testing by Western blot and [FA yielded a 99.7% correlation between these two methods. The authors recommend that in screening by ELISA as it is presently available, a low threshold (>2) should be established to maximize sensitivity and that positive results be confirmed by Western blot or IFA to maintain acceptable specificity. Serum samples from two low-risk groups (laboratory personnel and unselected blood donors) and four high-risk groups (asymptomatic homosexual men, hemophiliacs, ARC patients, and AIDS patients) were tested for the presence of antibodies to HTLV-II by three different serological assays. All specimens were first tested by ELISA. Every specimen with a P/N ratio of 2 or greater was further tested by Western blot and IFA, as were a sample of those with a P/N ratio less than 2. Descriptive findings are presented for each of the six groups. The study sample included as a low-risk group 1,014 healthy blood donors identified after blood bank screening procedures to exclude persons at 5B1-Car-10 Policy Keys: sone Ree. high risk for AIDS and 74 heterosexual laboratory and health care personnel with no known risk factors for AIDS. High-risk groups included 23 asymptomatic homosexual men, 45 hemophiliacs, 32 patients with ARC, and 69 patients with clinically diagnosed AIDS. 1) Blood Product Safety: Screening Tests and Assays (VBL), 2) Populations: Blood Donors, Health Care Workers (IA7), 3) Populations: Homosexuals, Hemophiliacs (IA 1,3) Author(s): Title: Source: Institutions Findings: Method: Sample Size: Policy Keys: Schupbach, Jorg, MD; Haller, Otto, MD; Vogt, Markus, MD; Luthy, Rudolf, MD; Joller, Helen, MD; Oelz, Oswald, MD; Popovic, Mikulas, MD; Sarngadharan, M.G., PhD; Gallo, Robert C., MD. Antibodies to HTLV-II in Swiss Patients with AIDS and Pre-AIDS and in Groups at Risk for AIDS. The New England Journal of Medicine, 31 January 1985, Vol. 312, No. 5: 265-270. Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland; Institute for Immunology and Virology, University of Zurich; Department of Medicine and Institute for Clinical Immunology, University Hospital, Zurich, Switzerland; Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland. Of 10 Swiss patients with AIDS and 10 with pre-AIDS, all were positive for antibody to human T-cell lymphotropic virus type III (HTLV-II). Other subjects who tested positive were 37 of 103 (36%) intravenous drug addicts, 4 of 40 (10%) healthy homosexual men, 7 of 83 (8.4%) patients with various types of hepatitis, but none of 83 healthy blood donors or 10 other controls tested positive. Antibodies to one type of HTLV-III protein (p24) were consistently high in the seropositive members of the groups at risk for AIDS and in the pre- AIDS group, but dramatically reduced in those with AIDS. In contrast, antibodies to another HTLV-II protein (p41) were present in all cases of AIDS and pre-AIDS but were absent in nearly 10% of seropositive persons at risk for AIDS. The enzyme-linked immunosorbent assay (ELISA) may be useful as a screening test for blood donors even though persons with full-blown AIDS frequently test negative by this assay, because presum- ably such patients will not be present among blood donors. Because of its high false-positive rate, the ELISA should not be used for purposes other than screening without confirmation by a viral assay. ELISA and two assays based on Western blot techniques (virus-strip radioimmunoassay and cell-strip radioimmunoassay) were used to test blood serum samples for antibodies to proteins associated with HTLV- III. Descriptive data and case-control comparisons were presented. Ten AIDS patients, 10 pre-AIDS cases, 103 intravenous drug addicts, 83 hepatitis patients, 40 healthy homosexuals, and 83 healthy blood donor controls were included. 1) Blood Product Safety: Screening Tests and Assays (VBL), 2) Geographic Trends: Europe (Switzerland) (IB4), 3) Blood Product Safety: Seroprevalence (VB2) 5B1~8ch-11 Author(s): Title: Source: [nstitution: Findings: Weiss, Stanley H., MD; Goedert, James J., MD; Sarngadharan, M.G., PhD; Bodner, Anne J., PhD; The AIDS Seroepidemiology Collaborative Working Group (Biggar, Robert J., MD; Clark, Jeffrey W., MD; Dodd, Roger Y., PhD; Gelmann, Edward P., MD; Giron, Jose S., MD; Greene, Mark H., MD; Melbye, Mads, MD; Popovic, Mikulas, PhD; Robert-Guroff, Marjorie, PhD; Saxinger, W. Carl, PhD; Simberkoff, Michael, MD; Winn, Deborah M., PhD); Gallo, Robert C., MD; Blattner, William A., MD. Screening Test for HTLV-II (AIDS Agent) Antibodies: Specificity, Sensitivity, and Applications. Journal of the American Medical Association, 11 January 1985, Vol. 253, No. 2: 221-225. Environmental Epidemiology Branch, Division of Cancer Etiology (Weiss, Goedert, Blattner, Biggar, Clark, Greene, Winn), the Medicine Branch (Gelmann) and Laboratory of Tumor Cell Biology, Division of Cancer Treatment (Gallo, Popovic, Robert-Guroff, Saxinger), National Cancer Institute, Bethesda, Maryland; Biotech Research Laboratories, Rockville, Maryland (Bodner); Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland (Sarngadharan); Flushing Hospital, Flushing, New York (Giron); American Red Cross Blood Services Laboratories, Bethesda, Maryland (Dodd); Institute of Cancer Research, Aarhus, Denmark (Melbye); Department of Infectious Disease, New York Veterans Administration Medical Center, New York, New York (Simberkoff). To test its use as a screening test among blood donors and populations at risk, and as a diagnostic indicator of suspected AIDS, an enzyme-linked immunosorbent assay (ELISA) for antibodies to human T-cell lymphotropic virus type III (HTLV-II) was tested. Blood serum samples from healthy blood donors were analyzed to determine the range of normal values of the ELISA ratio in testing for HTLV-II antibodies. Since the ELISA ratio was less than 5.0 in 99% of these control samples, ratios of 5.0 or greater were defined as positive, while ratios of less than 3.0 were defined as negative (92.6% of controls). The intermediate ratios (3.00 to 4.99) were defined as borderline. The seven positive results were assumed to represent false- positives after being found negative by a Western blot test. Of 88 AIDS patients who were tested for HTLV-III antibodies with these ELISA ratios, 72 (82%) were positive, 14 (16%) were borderline, and 2 (2%) were negative. Among persons at high risk for AIDS, 1% had borderline results, with positive and negative results readily distinguished as bimodal distributions (50% positive and 42% negative) that paralleled the temporal and geographic trends of AIDS. None of the specimens from 188 laboratory and health care employees working with AIDS patients were positive for HTLV-II antibodies. Defining AIDS patients with negative ELISA ratios as false-negative and healthy blood donors with positive ratios as false-positive, and excluding borderline ratios from analysis, the test is 98.6% specific and 97.3% sensitive for AIDS. The ELISA is both highly specific and sensitive and should be considered 5B1-Wei-12 Method: Sample Size: Policy Keys: a reliable initial screening test for the presence of antibodies, and hence exposure, to HTLV-IIIL. Serum samples of all subjects were analyzed by an ELISA to detect antibodies to HTLV-II. Western blots of purified HTLV-III proteins were also performed for some subjects to confirm findings. The 297 healthy blood donors consisted of 228 (78% male) self-selected blood donors in Burlington, Vermont, and 69 males in Aarhus and Copenhagen, Denmark. The AIDS patients consisted of 51 homosexual or bisexual men with Kaposi's sarcoma and 37 with only opportunistic infection (9 heterosexual men, 2 bisexual men, 3 heterosexual female intravenous drug users, 13 homosexual men, 4 Haitians, 4 hemophiliacs, | female sexual partner of a bisexual man, and 1 man who had received blood transfusions). One hundred and thirty-one people from high-risk groups in New York and 188 laboratory and health care workers were also included as separate groups. 1) Blood Product Safety: Screening Tests and Assays (VBI) V. Risk Reduction B. Blood Product Safety 2. Seroprevalence and Virus Isolation Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Groopman, Jerome E.; Chen, Francis W.; Hope, James A.; Andrews, Judith M.; Swift, Robert L.; Benton, Charles V.; Sullivan, John L.; Volberding, Paul A.; Sites, Daniel P.; Landesman, Sheldon; Gold, Jonathan; Baker, Louis; Craven, Donald; Boches, Francee S. Serological Characterization of HTLV-II Infection in AIDS and Related Disorders. The Journal of Infectious Diseases, April 1986, Vol. 153, No. 4: 736-742. Division of Hematology/Oncology, Department of Medicine, New England Deaconess Hospital; Harvard Medical School; Division of Infectious Disease, Boston City Hospital; Boston University School of Medicine, Boston, Massachusetts; Research and Development Department, Travenol-Genentech Diagnostics, Cambridge, Massachusetts; Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; Departments of Molecular Biology and Clinical Research, Genentech, South San Francisco, California; Departments of Medicine and Pathology, San Francisco General Hospital, University of California, San Francisco, California; Division of Infectious Disease, Downstate Medical Center, State University of New York Downstate, Brooklyn, New York; Division of Infectious Disease, Memorial Sloan-Kettering Cancer Institute, New York, New York. Current efforts to test blood donors and other persons for exposure to human T-cell lymphotropic virus type III (HTLV-II) are based on the measurement of serum antibodies to viral antigens. This study examined 767 individuals with AIDS or AIDS-related complex (ARC) and asympto- matic persons at risk for AIDS by the enzyme-linked immunosorbent assay (ELISA) and immunoblot assay techniques. Blood samples from the 280 subjects with AIDS or ARC showed 99% to be ELISA reactive and 96% immunoblot reactive. This study's large number of subjects (767) demonstrates virtual uniformity of antibodies to the reported correlated antigens throughout the clinical spectrum of HTLV-Ill-related disorders. The study also supports the authors' conclusion that it is unlikely that a specific serological pattern can distinguish symptomatic from asympto- matic HTLV-II infection. In addition, study findings show that prolonged incubation of the sera in the immunoblot assay detects low-titered and low-affinity antibodies that would be missed by previously published methods. Specimens from all study subjects and control sera were tested by ELISA and the immunoblot assay. For the immunoblot assay, the authors used a longer (overnight) incubation time than specified in published procedures. Results are compared by serum donor status. A total of 767 subjects were studied: 169 with AIDS, 111 with ARC, 295 healthy homosexual men, 67 hemophiliacs, 91 intravenous drug abusers, and 34 subjects who were the sexual contacts of patients with AIDS. Sera from 50 persons with disorders that often produce cross-reacting antibodies were tested as controls. 1) Blood Product Safety: Seroprevalence, Screening Tests and Assays (VB2,1) 5B2-Gro-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Mayer, Kenneth H., MD; Stoddard, Anne M., ScD; McCusker, Jane, MD, DrPH; Ayotte, David, MSPH; Ferriani, Roberta, BA; Groopman, Jerome E., MD. Human T-Lymphotropic Virus Type III in High-Risk, Antibody-Negative Homosexual Men. Annals of Internal Medicine, February 1986, Vol. 104, No. 2: 194-196. Fenway Community Health Center, Boston; Department of Medicine, New England Deaconess Hospital, Boston; Harvard Medical School, Boston, Massachusetts; Division of Public Health, University of Massachusetts, Amherst, Massachusetts; Department of Medicine, Memorial Hospital, Pawtucket, Rhode Island; Brown University, Providence, Rhode Island. A cohort of 215 asymptomatic homosexually active men from the Boston area was prospectively followed up to assess the natural history of human T-cell lymphotropic virus type III (HTLV-II) infection. To determine whether antibody-negative persons may be harboring the virus, an algorithm was developed that defined high-risk characteristics: a sexual partner with AIDS, more than 100 lifetime homosexual partners, leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Of 33 asymptomatic homosexual men who did not have HTLV-II antibodies, two had HTLV-III recovered from their lymphocytes. The authors suggest that the fact that high-risk seronegative persons may carry HTLV-II but be asymptomatic underscores the need to base preventive educational strategies and behavioral modification on the assessment of risk factors and not solely on the results of antibody screening. (Reviewer Note: Both seronegative subjects from whom HTLV-II was recovered seroconverted shortly after publication of this article.) This study consists of ongoing prospective long-term follow-up of homosexual men who tested negative for HTLV-II antibodies. All subjects completed a behavioral and demographic questionnaire, which included a detailed history of sexual practices, and had a complete physical exam. Blood was drawn for complete blood count, differential, and test for antibody to HTLV-II by enzyme-linked immunosorbent assay. A group of 215 initially healthy Boston area homosexual men were studied, 113 of whom were negative for HTLV-III antibodies when first seen (January to June 1985). Of the 113 eligible subjects, 33 participated in the viral isolation study. These 33 men met one of the following criteria: sexual partner with AIDS, more than 100 lifetime sexual partners, leukopenia, lymphopenia, neutropenia, or thrombocytopenia. 1) Seroprevalence and Virus Isolation: Antibody Negative, but Virus Positive (VB2), 2) Populations: Homosexuals (IA1) 5B2-May-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Lindhardt, B. Orskov; Ulrich, K.; Ryder, L.; Dickmeiss, E.; Sorensen, H.; Jorgensen, J.; Jersild, C.; Grunnet, N. HTLV-II Antibody Testing in Three Danish Blood Banks. Vox Sanguinis, 1986, Vol. 51, Suppl. 1: 9-14. Laboratory of Tumor Virology, Fibiger Institute, Copenhagen (Lindhardt, Ulrich); Department of Clinical Immunology, University Hospital, Copenhagen (Ryder, Dickmeiss, Sorensen); Blood Bank, Aarhus Kommunehospital, Aarhus (Jorgensen); Blood Bank, Aalborg Sygehus Nord, Aalborg, Denmark (Jersild, Grunnet). To estimate the frequency of positive and false-positive reactions, blood donor specimens were tested by a commercially available enzyme-linked immunosorbent assay (ELISA) for antibodies to human T-cell lymphotropic virus type III (HTLV-II), and factors affecting test results were Investigated. Of 3,940 sera screened by the Vironostika test, 23 were positive initially when a low cutoff was used. By a second test, 12 of these 23 samples were repeatedly positive. When tested by Western blot, none of these samples contained specific antibodies against HTLV- [IT proteins. Of 2,302 sera screened by the noncommercial ELISA, 38 were positive or equivocal at first testing and 8 were positive twice. None of these were positive by Western blotting. When testing different categories of patients, only sera containing human leukocyte antigen (HLA) antibodies gave rise to false-positive reactions. Important differ- ences in the results were observed for sample preparation (i.e., lack of centrifugation before testing), single- or dual-wavelength optical density readings, the experience of the technical staff, and insufficient washing procedures. Blood serum samples were screened for HTLV-II antibodies by the Organon Teknika Vironostika ELISA test. For comparison, some of these specimens were also tested by a noncommercial ELISA. Results were confirmed by Western blot. Sera from two blood banks were centrifuged before being stored at -20°C, but sera from the third blood bank were not centrifuged. Sera from Danish blood donors were consecutively collected in three blood banks. Blood bank A provided 1,441 sera; blood bank B, 1,413 sera; and blood bank C, 1,086 sera. Also included were 100 serum samples which were positive for hepatitis B virus surface antigen by a commercial ELISA in blood bank C but negative when tested by a con- firmatory, commercial radioimmunoassay. Finally, 90 sera from patients with various autoimmune diseases, dialysis patients, anti-HLA-DR#4- positive patients, and other different diseases were tested. 1) Blood Product Safety: Seroprevalence, Screening Tests and Assays (VB2,1), 2) Geographic Trends: Europe (Denmark) (IB4) 552-1Lin-3 Author(s): Title: Source: Institution: Findings: Method: Nusbacher, Jacob; Chiavetta, Joanne; Naiman, Renee; Buchner, Barbara; Scalia, Vito; Herst, Roslyn. Evaluation of a Confidential Method of Excluding Blood Donors Exposed to Human Immunodeficiency Virus. Transfusion, 1986, Vol. 26, No. 6: 539-541. Toronto Centre and National Reference Laboratory, Canadian Red Cross Blood Transfusion Service, Toronto, Ontario, Canada. Despite the good intentions of blood donors, donors who should not give occasionally do so. One reason may be group pressure and the desire not to be labeled "abnormal™ in any way. This study examines one method for blood collection agencies to exclude dangerous donors without stigmatization or embarrassment. After the usual procedure of registration, routine medical screening (which includes reading a pamphlet describing AIDS high-risk groups), and hemoglobin determina- tion, donors were given a questionnaire to fill out. Questionnaires were completed privately and confidentially and asked donors to check a box designating his or her blood to be "used for transfusion into patients" or "used for laboratory purposes only." Of the 95,917 donors who filled out questionnaires, 627 designated their blood for laboratory purposes only. The laboratory designation group had a 10 times greater likelihood of being positive for antibody to human immunodeficiency virus (HIV) by enzyme immunoassay (EIA), as con- firmed by Western blot, but had fewer false-positive results by EIA than a control group matched for age, gender, and donor clinic site. Compared with the donor population in general, their rate of seropositiv- ity was 100 times greater. Therefore, the confidential self-designation form identified a group of donors who are more likely to transmit HIV. Even after reading a pamphlet that asks high-risk persons not to give blood, 0.65% of donors having passed this phase of predonation screening still believed they were in a high-risk group. One donor in the laboratory designation group was found to be positive by Western blot, even though the EIA screening result was negative. Because HIV antibody screening is performed for all donors, does the use of the self-designation questionnaire further increase the safety of the blood supply? In this study, one donation slipped by the EIA screening process, but was not used for transfusion because the donor had desig- nated it for laboratory use. Extrapolating from this one case, the authors calculate 16 false-negative EIA tests per 1,000,000 blood donors. In addition to usual predonation screening and regular EIA testing of all donations, all blood donors were asked to fill out a questionnaire which included the designation of his or her blood for transfusion purposes or for laboratory use only. Questionnaires were returned to the blood processing laboratory and opened there. Units of blood designated for laboratory purposes only were removed from inventory and not used for transfusion. Otherwise, all procedures were the same for all donors. All donor specimens were tested for HIV antibody by EIA. All repeatedly 5B2-Nus-4 Sample Size: Policy Keys: positive units were removed from the transfusion supply. All samples from the laboratory designation group and from a control group were also tested by Western blot analysis. All 95,917 volunteer donors presenting themselves at fixed and mobile donation sites in the central Ontario region, Canada, were subjects of this study. The study period extended from 27 September 1985 to 31 March 1986. The control group consisted of a subset of 625 donors who were chosen each day during this period and matched for age, gender, and clinic site with the 627 donors who had designated their blood for laboratory purposes only. 1) Blood Product Safety: Seroprevalence (VB2) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Sayers, Merlin H.; Beatty, Patrick G.; Hansen, John A. HLA Antibodies as a Cause of False-Positive Reactions in Screening Enzyme Immunoassays for Antibodies to Human T-Lymphotropic Virus Type III. Transfusion, 1986, Vol. 26, No. 1: 113-115. Puget Sound Blood Center; Fred Hutchinson Cancer Research Center; University of Washington, Seattle, Washington. This study was conducted to investigate the possible role of human leukocyte antigen (HLA) antibodies as a cause of false-positive reactions in the screening test for human T-cell lymphotropic virus type III (HTLV- III) antibody. Screening of 15,680 volunteer blood donors by enzyme- linked immunosorbent assays (EIAs) for HTLV-III antibody revealed 0.85% initially reactive and 0.37% reactive on at least two of three determinations. The first 38 of the repeatedly reactive samples were sent for repeat EIA and confirmatory testing by Western blot; of these, the EIA was positive in 14. Western blot confirmed positive results for only 3 of the 14 samples. (No test subjects were EIA negative and Western blot positive.) Eight of these 11 false-positive samples were from women who were found to have HLA antibodies, and in 7 of these women the HLA antibodies were directed to class ll antigens expressed on the parent cell that is used to culture the virus in preparing the screening tests. The authors note that less than 1% of women with a history of pregnancy would have such antibodies and get false-positive results with the EIA test. The study demonstrates that anti-HLA anti- bodies are a cause of false-positive results in the EIA test for HTLV-III antibody, and emphasizes the need for confirmatory testing to avoid the risk of labeling noninfectious donors as carriers of AIDS antibody. Initial blood screening was conducted by EIA testing (Abbott). The first 38 repeatedly reactive samples were sent to laboratories (Abbott) for repeat EIA and confirmatory testing by Western blot. Eleven samples that were positive by EIA and Western blot negative were then screened for antibodies with HLA specificity and also against the human T-cell leukemia line HUT-78 (H9 cells), which is the cell line used by Abbott Laboratories for culturing the HTLV-III used in their test kits. The study sample included the first 38 blood samples repeatedly reactive on screening for antibody to HTLV-II. Samples were collected during screening of 15,680 volunteer blood donors presenting during a 6-week period at the Puget Sound Blood Center in Seattle, Washington. Donors were told that blood would be tested for HTLV-III antibody and that test results would not be released. Donors were asked to disqualify them- selves either before or after donation if they were members of a high- risk group. Alternative test sites were available for individuals wishing to know whether they were seropositive. 1) Blood Product Safety: Causes of false positive antibody results (VB2), 2) Populations: Blood Donors (IA7) 5B2-Say-5 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Ross, Michael W.; Drew, Paul A.; Beal, Robert W. Characteristics of Homosexual Men Who Donate Blood. The Medical Journal of Australia, 18 March 1985, Vol. 142: 343-344, Department of Psychiatry, Flinders University Medical School, Bedford Park, South Australia (Ross); Department of Medicine, University of Adelaide Medical School, Adelaide, South Australia (Drew); Red Cross Blood Transfusion Service, Adelaide, South Australia (Beal). Before a sensitive and specific test to detect human T-cell lymphotropic virus type III (HTLV-II) was widely available, blood banks in Australia had to trust that individuals at high risk would refrain from donating blood. In March 1984, the Australian Red Cross asked people with any homosexual encounters in the last 5 years to refrain from donating. In this report, homosexual men who reported donating blood before March 1984 were compared with homosexuals who did not donate. Comparison between those who had donated blood in the past 5 years with those who had donated in the past year showed that 18 were constant donors throughout this period, 7 new individuals joined the donor pool in the past year, and 4 homosexual men stopped giving blood. (Blood donation among homosexual men is much more common than among the general population. This may be explained partly by their high education levels and their age range.) Among the respondents, blood donors were significantly younger and had been homosexually active for a shorter period, but had been involved in the homosexual subculture longer than the nondonors. Donors were also significantly less likely to have had a sexually transmitted disease and less likely to have contacted their sexual partners in an anonymous setting (such as a sauna) than nondonors. The data do not confirm the suggestion that male homosexual blood donors as a group are psychologically different from male homosexual nondonors. Participants were asked to complete a questionnaire and to donate a sample of blood as part of a research study of the immunological and psychological health of homosexual men. The authors point out, however, that the study sample was unlikely to include homosexual men with no contact with gay organizations, bisexuals, and those who do not consider that the term homosexual applies to them. The questionnaires were completed by 97 homosexual men in Adelaide in the first quarter of 1984. Subjects were contacted through homosexual social clubs, saunas, newsletters, churches, sports clubs, and the sexually transmitted disease clinic. The mean age was 33.8 years (range, 19 to 54). The majority (75%) were born in Australia, 15% in the United Kingdom, and 3% in New Zealand, plus one or two individuals each from West Germany, the U.S., Malaysia, Singapore, and Egypt. 1) Blood Product Safety: Voluntary Screening (VB2), 2) Populations: Homosexuals (IA1), 3) Geographic Trends: Australia (IB3) 5B2-Ros-6 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Contreras, Marcela, BSC, MD; Hewitt, Patricia E., MRCP, MRCPATH; Barbara, John A.J., MSC, PhD; Mochnaty, Peter Z., BSC. Blood Donors at High Risk of Transmitting the Acquired Immune Deficiency Syndrome. British Medical Journal, 9 March 1985, Vol. 290: 749-750. North London Blood Transfusion Centre, Edgeware, Middlesex, England. Education of blood donors was undertaken in an attempt to minimize the donation of potentially contaminated blood by persons at high risk for AIDS. A leaflet was developed describing the importance of AIDS and listing high-risk groups, particularly homosexual men, who should refrain from donating. Despite these educational efforts, some homosexual men still donated blood. At a clinic in West London, donors were given a leaflet and completed a questionnaire in private as well. Those who considered themselves to be in a high-risk group were asked to designate their blood for research purposes only. All donors belonging to a high-risk group were male, and homosexuality was the only risk factor named. Of 5,000 questionnaires administered between July and October 1984, 614 were not completed or had ambiguous answers. Overall, thirty-eight donors who completed the questionnaire belonged to a high-risk group; none were positive for antibody to human T-cell lymphotropic virus type III (HTLV-II), Treponema pallidum (the agent of syphilis) hemagglutination, or hepatitis B virus surface antigen, but seven were positive for antibody to hepatitis B virus core antigen. Of the 2,333 men who did not categorize themselves as high risk, | was positive for T. pallidum hemagglutination and | for hepatitis B virus surface antigen. Between July and October 1984 a leaflet on AIDS and a questionnaire were given to all donors attending a blood donor clinic in the west end of London; 87% had given blood previously, and 53% were male. Those who considered themselves to be in a high-risk group were asked to designate their blood for research purposes only. These donors were subsequently interviewed in private by a medical officer. Serum samples from high- risk donors were tested for antibody to hepatitis B virus core antigen and HTLV-II. Of 5,000 questionnaire takers, 38 belonged to a high-risk group. All were male, and homosexuality was the only risk factor. 1) Blood Product Safety: Seroprevalence (VB2), 2) Information/Educa- tion: Risk Behaviors and Protection (VA2), 3) Populations: Blood Donors (IA7) 5B2-Con-7 Author(s): Title: Source: Institution: Findings: Method: Sample Size: McDougal, J. Steven; Jaffe, Harold W.; Cabridilla, Cirilo D.; Sarngadharan, M.G.; Nicholson, Janet K.A.; Kalyanaraman, V.S.; Schable, Charles A.; Kilbourne, Barbara; Evatt, Bruce L.; Gallo, Robert C.; Curran, James W. Screening Tests for Blood Donors Presumed to Have Transmitted the Acquired Immunodeficiency Syndrome. Blood, March 1985, Vol. 65, No. 3: 772-775. Division of Host Factors and the Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland. To evaluate the ability of blood tests to detect AIDS "carriers," 18 sets of blood donors were investigated from 12 to 50 months after they donated blood to recipients who subsequently developed AIDS. Donor sets with one donor who was a member of an AIDS risk group were selected, and that donor was labeled the suspected donor while the others were nonsuspected donors. A number of laboratory tests distinguished suspected from nonsuspected donors. Findings showed that 83.3% of suspected donors had low helper/suppressor T-cell ratios, compared with only 1.1% of the nonsuspected donors; 62.5% of the suspected donors had antibody to hepatitis B virus core antigen, compared with 6.3% of the nonsuspected donors. The most sensitive and specific tests for dis- tinguishing suspected from nonsuspected donors were tests for human T- cell lymphotropic virus type III (HTLV-II) antibodies. Test results showed that 93.8% of suspected donors were positive by enzyme-linked immunosorbent assay (ELISA), 100% by Western blot, and 77.8% by radioimmunoprecipitation, compared with 1.7%, 0.8%, and 2.7%, respectively, of nonsuspected donors. Data were relatively quickly obtained and support the concept of screening. A number of measures to distinguish between infected and uninfected blood serum samples were used, including antibody to hepatitis B virus core antigen, helper/suppressor T-cell ratio, the Staphylococcus-binding assay for immune complexes, and four assays for antibody to HTLV-III or lymphadenopathy-associated virus (LAV): an anti-HTLV-III ELISA, an anti-HTLV-IIl Western blot, an anti-LAV Western blot, and an anti-LAV radioimmunoprecipitation assay. Suspected and nonsuspected donors were compared. Eighteen sets of blood donors, each set having contributed blood products to a recipient who subsequently developed AIDS, were selected for study. Seventeen donor sets fulfilled the following criteria: (1) donor investigations were completed, (2) a single donor per case was identified as the likely transmitter, and (3) donor blood was available 12 to 50 months after donation for testing. An additional donor was included because he gave blood to a patient who developed AIDS and subsequently developed AIDS himself. Of the 18 suspected donor transmitters, 14 were homosexual men, 3 were intravenous drug abusers, and | was of unknown risk factor. Three had developed lymphadenopathy, and two had 5B2-McD-8 developed AIDS. The nonsuspected donors totaled 189 subjects used as controls. Policy Keys: 1) Blood Product Safety: Seroprevalence (VB2), 2) Transmission: Blood Transfusions (IIC) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Pindyck, J.; Waldman, A.; Zang, E.; Oleszko, W.; Lowy, M.; Bianco, C. Measures to Decrease the Risk of Acquired Immunodeficiency Syndrome Transmission by Blood Transfusion: Evidence of Volunteer Blood Donor Cooperation. Transfusion, 1985, Vol. 25, No. 1: 3-9. Greater New York Blood Program, The New York Blood Center, New York, New York. This study examined whether volunteers donating blood to the Greater New York Blood Program cooperated with procedures to decrease AIDS transmission in the blood supply. Such measures were necessary because no definitive test for the AIDS virus was available at the time. The number of male donors decreased between 1982 and 1983, when this effort was initiated; AIDS-related questions in the medical history questionnaire led to a 2% increase in donor rejections; 97% of donors said their blood could be used for transfusions; 1.4% said their blood could be used only for laboratory studies; and 1.6% did not respond. Only units designated for transfusion were released to hospitals. Donors who indicated that their donation was for laboratory studies had a higher prevalence of antibodies to hepatitis B virus and cytomegalo- virus. White cell counts and T-cell ratios were not different in the two groups. The authors conclude that volunteer donors have cooperated with the established procedures. This study compared the donor population after institution of a program for screening blood donors to exclude people at risk for AIDS by questionnaires, medical histories, and immunological testing of blood samples with the donor population of a base period | year earlier. Each prospective volunteer donor in 1983 (the study period) first underwent a medical evaluation that included questioning about history of infectious diseases and intravenous drug abuse, recent weight loss, unexplained fever and cough, as well as other AIDS-related symptoms. All donors who passed this screening were given confidential forms to complete that described AIDS high-risk groups and asked for a self-evaluation of suitability of the donated blood for transfusion. Routine lab tests were performed on blood some samples. Blood donors in Greater New York (New York City, Long Island, the lower Hudson valley, and parts of northern New Jersey) in 1982 were compared with those from 14 March to 22 May 1983 (study period). In the base period, there were 88,404 donors, 62.2% of them male, while in the study period there were 89,389 donors, 61.5% of them male. 1) Blood Product Safety: Voluntary Screening (VB2), 2) [Information/Education: Risk Behaviors and Protection (VA2), 3) Populations: Blood Donors (IA7) 5B2-Pin-9 Author(s): Titles Source: Institution: Findings: Method: Sample Size: Policy Keys: Salahuddin, S. Zaki; Markham, Phillip D.; Redfield, Robert R.; Essex, M.; Groopman, Jerome E.; Sarngadharan, M.G.; McLane, Mary F.; Sliski, Ann; Gallo, Robert C. HTLV-III in Symptom-Free Seronegative Persons. The Lancet, 22/29 December 1984, Vol. 2, No. 8417/8: 1418-1420. Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Division of Hematology/Oncol- ogy, Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts; Department of Cell Biology, Litton Bionetics Inc., Kensington, Maryland; Department of Virus Diseases, Walter Reed Army Institute of Research, Washington, DC; Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts. During a previous study to identify people previously exposed to human T-cell lymphotropic virus type III (HTLV-II), 96 subjects were found to harbor the virus in blood cells or body fluids (e.g., saliva, semen, or plasma). However, four had no detectable antibodies to viral proteins (antibody negative), although HTLV-II itself was isolated from their white blood cells (virus positive). Three of these subjects were symptom free, and one had lymphadenopathy. Three of the subjects who were negative for antibodies to HTLV-II (two homosexuals and one woman) were sexual partners of men diagnosed with AIDS or AIDS-related complex (ARC); the fourth was the 6l-year-old wife of a man with AIDS. The couple had not had sexual intercourse in 3 years, but they had exchanged saliva by kissing. Study findings suggest that assays other than those detecting antibody to virus, perhaps based on detection of viral antigens or immune complexes, may be required to identify all infected individuals. Blood serum samples were collected and tested for the presence of antibody to HTLV-II structural proteins by indirect membrane immunofluorescence, enzyme-linked immunosorbent assay, and Western blot procedures. Samples reacting with viral antigens by any of these tests were considered positive. Patient white blood cells were also tested for HTLV-III itself. Ninety-six people with AIDS, with ARC, or at risk for AIDS who were found to harbor HTLV-II in blood cells or body fluids were studied. A subset of four, who had no antibodies to HTLV-III despite having the virus itself in their blood cells, consisted of two homosexual men whose partners were diagnosed with AIDS and two women, one whose husband had transfusion-associated AIDS and one whose sexual partner had ARC. 1) Seroprevalence and Virus Isolation: Antibody-Negative but Virus- Positive (VB2), 2) Transmission: Saliva (IIG), 3) Other Characteristics of Disease: HTLV-II in Saliva and Semen (IIIF) 5B2-Sal-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Gallo, Robert C.; Salahuddin, Syed Z.; Popovic, Mikulas; Shearer, Gene M.; Kaplan, Mark; Haynes, Barton F.; Palker, Thomas J.; Redfield, Robert; Oleske, James; Safai, Bijan; White, Gilbert; Foster, Paul; Markham, Phillip D. Frequent Detection and Isolation of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and at Risk for AIDS. Science, 4 May 1984, Vol. 224: 500-503. Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Gallo, Salahuddin, Popovic); Immunology Branch, National Cancer Institute (Shearer); Division of Infectious Diseases, North Shore University Hospital, Manhasset, New York (Kaplan); Department of Medicine, Duke University School of Medicine, Durham, North Carolina (Haynes, Palker); Department of Virus Diseases, Walter Reed Army Institute of Research, Washington, DC (Redfield); Division of Allergy, Immunology, and Infectious Disease, University of Medicine and Dentistry of New Jersey, Newark (Oleske); Dermatology Service, Memorial Sloan Kettering Cancer Center, New York (Safai); Department of Medicine, University of North Carolina, Chapel Hill (White, Foster); Department of Cell Biology, Litton Bionetics, Inc., Kensington, Maryland (Markham). The presence of human T-cell lymphotropic virus type III (HTLV-II) in AIDS patients and those at risk was studied. HTLV-III was found in 18 of 21 blood samples from patients with pre-AIDS syndrome, in 3 of 4 samples from clinically normal mothers of juvenile AIDS patients, in 3 of 8 samples from juvenile AIDS patients, and in 23 of 64 samples from adult AIDS patients. Virus was detected in only | of 22 samples from clinically normal, nonpromiscuous homosexual males. Six months after these tests, the one positive normal homosexual subject developed AIDS. Virus was not detected or isolated from any of 115 normal volunteers. In this study, peripheral blood lymphocytes from subjects were grown in the laboratory with added T-cell growth factor. Evidence for the presence of HTLV-III included: viral reverse transcriptase activity in supernant fluids, transmission of virus by coculturing T cells with irradiated donor cells or with cell-free fluids, observation of virus by electron microscopy, and the expression of viral antigens in indirect immune fluorescence assays using serum from a patient positive for antibodies to HTLV-IIl, or antisera prepared against purified, whole disrupled HTLV-III. A total of 234 subjects were tested, including 21 patients with pre-AIDS, 4 mothers of juveniles with AIDS, 8 juvenile and 64 adult AIDS patients, 22 clinically normal, nonpromiscuous homosexual males, and 115 normal heterosexuals. 1) Seroprevalence: Identification of Causative Agent (VB2) 5B2-Gal-11 V. Risk Reduction B. Blood Product Safety 3. Inactivation of Virus po Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Jungkind, Donald L.; DiRenzo, Sue A.; Young, Shelly J. Effect of Using Heat-Inactivated Serum with the Abbott Human T-Cell Lymphotropic Virus Type III Antibody Test. Journal of Clinical Microbiology, February 1986, Vol. 23, No. 2: 381-382. Clinical Microbiology Laboratory, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. The Abbott enzyme immunoassay (EIA) was evaluated to determine the effect of using heat-inactivated (56°C for 30 minutes) serum as the test sample. Each of 58 nonreactive serum samples gave a higher absorbance value at 492 nm when tested after heat inactivation. Ten of the samples from healthy persons became reactive after heating. Seven of the ll heat- treated AIDS samples gave higher absorbancy values than the unheated AIDS samples. This study determined that heating serum to inactivate the human T-cell lymphotropic virus type III (HTLV-II) should not be used when the current Abbott HTLV-II antibody test is performed by the current method because the use of heat-inactivated serum can lead to false- positive test results. In this laboratory study, all serum samples were refrigerated before testing and then split: one portion was heated in a water bath at 56°C for 30 minutes and then cooled to room temperature; the remainder was kept at 4°C and then warmed to room temperature before testing. The Abbott EIA test kit was used to test for antibodies to HTLV-II. Blood samples from 58 healthy donors in non-high-risk groups for AIDS and from 11 AIDS patients were studied. 1) Blood Product Safety: Inactivation of Virus (VB3), 2) Blood Product Safety: Screening Tests and Assays (VB1) 5B3-Jun-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Hilfenhaus, Joachim; Herrmann, Annelise; Mauler, Rudolph; Prince, Alfred M. Inactivation of the AIDS-Causing Retrovirus and Other Human Viruses in Antihemophilic Plasma Protein Preparations by Pasteurization. Vox Sanguinis, 1986, Vol. 50: 208-211. Research Laboratories of Behringwerke AG, Marburg, Federal Republic of Germany; Lindsley F. Kimball Research Institute of the New York Blood Center, New York. This study tested the effectiveness of pasteurization (heat treatment) which was originally used in manufacturing cryoprecipitate (cold- precipitated plasma) and factor VIII clotting-factor concentrates to reduce the risk of transmission of hepatitis, in inactivating human T-cell lymphotropic virus type III (HTLV-II). HTLV-II was readily inactivated by being heated to 60°C in the liquid state, becoming nondetectable in 30 minutes in cryoprecipitate and 60 minutes in factor VIII. Longer heat treatment was necessary to inactivate the virus in plasma protein con- taining high concentrations of stabilizers (glycine and sucrose) than for HTLV-II diluted in buffer solution. Pasteurization also completely inactivated cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and poliovirus, but not vaccinia virus (the pox virus used in immunization against smallpox). The authors conclude that neither AIDS nor any human herpesvirus infection is likely to be transmitted by pasteurized cryoprecipitate or factor VIII preparations. Samples of cryoprecipitate and factor VIII concentrates were taken from routine production lots directly before pasteurization and mixed with glycine and sucrose as stabilizers. These mixtures were then heat treated at 60°C for up to 10 hours. Samples were taken before and at various times during heat treatment and tested for the infectious viruses. HTLV-III was propagated and assayed in H9 cells. Other viruses tested were cytomegalovirus, Epstein-Barr virus, herpes simplex virus, poliovirus, and vaccinia virus. When no infectious virus was detected in culture after 21 days, the results were reported as no virus detectable. Not applicable. 1) Blood Product Safety: Inactivation of Virus (VB3), 2) Populations: Hemophiliacs (IA3), 3) Transmission: Blood Products (IIC) 5B3-Hil-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Quinnan, Gerald V., Jr.; Wells, Martha A.; Wittek, Alec E.; Phelan, Michael A.; Mayner, Ronald E.; Feinstone, Stephen; Purcell, Robert H.; Epstein, Jay S. Inactivation of Human T-Cell Lymphotropic Virus, Type III by Heat, Chemicals, and Irradiation. Transfusion, 1986, Vol. 26, No. 5: 481-483. Division of Virology, Office of Biologics Research and Review, Center for Drugs and Biologics, Food and Drug Administration, Bethesda, Maryland; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Methods of inactivating human T-cell lymphotropic virus type III (HTLV- II) by heat, chemicals, and irradiation were tested. Holding the virus at 37°C for 18 hours resulted in no loss of infectivity. Infectivity of HTLV-II was inactivated by heat more rapidly in liquid medium than when freeze-dried and more rapidly at 60°C than at 56°C. When HTLV-II was added to factor VIII clotting concentrate and then freeze-dried and heated to 60°C for 2 hours or longer, infectivity was reduced 1,000,000-fold. Infectivity of HTLV-II in factor VIII concentrate was also completely eliminated when chloroform was added after freeze-drying, even when the chloroform was removed immediately after it was added. HTLV-II was also inactivated by several other chemicals, as well as by ultraviolet light in the presence of psoralen. Production of factor VIII concentrate from plasma involves several steps, two of which were evaluated in this study: freeze-drying and specific viral inactivation procedures. The chloroform treatment used is not believed to affect the biologic activity of factor VIII, and the heat treatment used does not cause the samples to lose their clotting ability. Viral inactivation procedures currently used for commercial factor VIII concentrates include heating freeze-dried product at 60°C or 68°C, heating the product in the wet state at 60°C, and treatment with a certain chemical plus detergent. These results indicate that a variety of chemical and physical procedures are effective in reducing the infectiv- ity of HTLV-III. The procedures tested here were generally relevant to the safety of plasma derivatives, preparation of HTLV-II antigens for use in immunoassays, and environmental antisepsis. HTLV-II in clotting-factor concentrate was tested in vitro for methods of inactivation, such as heat, freeze-drying, chloroform, and irradiation with ultraviolet light. Not applicable. 1) Blood Product Safety: Inactivation of Virus (VB3) 5B3-Qui-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Hilfenhaus, Joachim; M uler, Rudolf; Friis, Robert; Bauer, Heinz. Safety of Human Blood Products: Inactivation of Retroviruses by Heat Treatment at 60°C. Proceedings of the Society for Experimental Biology and Medicine, 1985, Vol. 178: 580-584. Research Laboratories of Behringwerke AG, Marburg; Institute for Virology, Giesen, Federal Republic of Germany. The AIDS virus, human T-cell lymphotropic virus type III (HTLV-II), is a retrovirus, which can be transmitted to patients by blood transfusions or other blood preparations, such as the clotting factor VIII concentrate used by hemophiliacs. This study investigates whether heat treatment at 60°C will inactivate retroviruses such as HTLV-II. Because human retroviruses are not available in quantity, Rous sarcoma virus (from chicken embryos) was compared with two common mammalian viruses found to be very similar in deactivation properties. In all of eight different plasma protein preparations tested, the Rous sarcoma virus was completely inactivated after heat treatment lasting no longer than 4 hours. The authors conclude that heating (pasteurizing) liquid plasma protein preparations at 60°C for 10 hours will inactivate the AIDS virus, provided that the AIDS retrovirus has heat stability comparable to that of the Rous sarcoma virus and mammalian retro- viruses that were tested here. The authors conclude that these data present convincing evidence that heat treatment is an effective method of virus inactivation. Pasteurization was used to inactivate Rous sarcoma virus and two mammalian retroviruses in plasma protein. Pasteurization was conducted at 60°C for various time periods. At the end of heat treatment, all samples were assayed simultaneously for infectious virus. Not applicable. 1) Blood Product Safety: Inactivation of Virus (VB3) 5B3-Hil-4 V. Risk Reduction C. Infection Control in Occupational Settings Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Resnick, Lionel, MD; Veren, Keith; Salahuddin, S. Zaki, MS; Tondreau, Sue; Markham, Phillip D., PhD. Stability and Inactivation of HTLV-III[/LAV under Clinical and Laboratory Environments. Journal of the American Medical Association, 11 April 1986, Vol. 255, No. 14: 1887-1891. Laboratory of Tumor Cell Biology, National Institutes of Health, Bethesda, Maryland (Resnick, Salahuddin); Department of Cell Biology, Bionetics Research, Inc., Rockville, Maryland (Veren, Tondreau, Markham); Dermatology Department, Mount Sinai Hospital-Medical Center, Miami Beach, Florida (Resnick). The stability of human T-cell lymphotropic virus type III/lymphadeno- pathy-associated virus (HTLV-III/LAV) under the environmental condi- tions encountered in a clinical or lab setting and its inactivation by commonly used chemical disinfectants were investigated. Under the experimental conditions used by these researchers, who worked with a highly concentrated viral preparation, infectious virus can be recovered for more than a week from water held at room temperature or at 36°C to 37°C. The number of viruses recovered is reduced at a rate of approximately 1 log, TCIDg, every 20 minutes when held at 54°C to 56°C. Dried and held at room temperature, HTLV-II[/LAV remains infectious for more than 3 days. Viral infectivity is undetectable and reduced within 1 minute with 0.5% sodium hypochlorite, 70% alcohol, or 0.5% Nonidet-P40, and within 10 minutes with 0.08% quaternary ammonium chloride or with a 1:1 mixture of acetone-alcohol. According to the authors, these results provide a rational basis for preventing the accidental spread of HTLV-III/LAV in the lab or clinical setting. Infectivity of HTLV-II was tested under three types of conditions: heating, drying, and disinfecting with chemicals. HTLV-III was obtained from the blood of a patient with AIDS. Peripheral blood cells were obtained from healthy adults. To determine which cell cultures were infected, cells were monitored for characteristic cytopathic effect and supernatant fluids were assayed for particle-associated reverse transcriptase activity. Cell cultures were monitored for a minimum of 1 month. One milliliter of each dilution was exposed for 2 to 15 days at 23°C to 27°C (room temperature) and at 37°C and for 30 minutes to 5 hours at 56°C. One milliliter of each dilution was dried, covered, incu- bated at room temperature for up to 168 hours, and then reconstituted and tested for infectious virus. The chemical concentrations used were: quaternary ammonium chlorides in water to yield 0.08%; sodium hypochlorite diluted in water to 0.5%; Nonidet-P40 diluted to 0.5% in isotonic buffer; alcohol diluted to 70% in water; and methylalcohol and acetone mixed 1:1. Not applicable. 1) Infection Control in Occupational Settings (VC) 5C-Res-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Martin, Linda S.; McDougal, J. Steven; Loskoski, Sherry L. Disinfection and Inactivation of the Human T Lymphotropic Virus Type [[I/Lymphadenopathy-Associated Virus. The Journal of Infectious Diseases, August 1985, Vol. 152, No. 2: 400- 403. Immunology Branch, Division of Host Factors, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. The purpose of this study was to investigate inactivation of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV- I[II/LAV) by reagents and conditions commonly used in laboratories. A sensitive and quantitative bioassay for infectious virus was used to evaluate virus inactivation. Both the observed reduction in the concentration of infectious virus after exposure to disinfectants (interpreted by comparison with appropriate controls) and empirical estimates of efficacy derived by extrapolation from dose-response plots were used as indicators of inactivation of the virus. The results indicated that alcohols, hypochlorite, the detergent Nonidet P-40 (but not Tween 20), hydrogen peroxide, phenolics, and paraformaldehyde are all effective inactivators of HTLV-III/LAV at concentrations well below those usually formulated for use as a disinfectant or in the laboratory. HTLV-III/LAV was propagated in the lab in special cultures, and a microculture assay was used to determine the number of infectious HTLV-III/LAV organisms in a 50% infectious dose (the reciprocal of the dilution of virus at which 50% of the cultures are positive). The following inactivators were used: isopropyl rubbing alcohol (70%), ethyl alcohol, absolute alcohol, household bleach, Tween 20, methanol-free paraformaldehyde, Lysol, and hydrogen peroxide. For toxicity controls, separate tubes of virus and inactivator were first serially diluted and then inoculated together into cell cultures so that the final concentrations of virus and agent were identical to those in the Inactivation assay. Some concentrations of inactivators were futher evaluated with two additional subcultures of culture supernatant harvested after 8 to 10 days of virus growth. Supernatant (100 microliters) was removed from each of 10 microcultures that were monitored for virus replication for 24 to 26 days. Not applicable. 1) Infection Control in Occupational Settings (VC) 5C-Mar-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Spire, B.; Montagnier, L.; Barre-Sinoussi, F.; Chermann, J.C. Inactivation of Lymphadenopathy Associated Virus by Chemical Disinfectants. The Lancet, 20 October 1984, Vol. 2, No. 8408: 899-901. Viral Oncology Unit, Institut Pasteur, Paris, France. To evaluate their effectiveness in disinfection, standard chemical disinfectants were used to inactivate lymphadenopathy-associated virus (LAV). Results indicate that 25% ethanol or 1% glutaraldehyde should prove sufficient to disinfect medical instruments, 0.2% sodium hypochlorite (bleach) is sufficient to clean floors and benches, and 0.1% Formalin proved too slow for any disinfection application in this study. Formalin is therefore not recommended for inactivation of LAV. In this laboratory study, since there was no accurate and sensitive test at the time for infectivity of LAV, reverse transcriptase was used as an indicator of viral inactivation. The chemical disinfectants tested were ethanol, bleach, Formalin, glutaraldehyde, and B-propionolactone. Not applicable. 1) Infection Control in Occupational Settings (VC) 5C-Spi-3 S— Emm — =r VI. Related Policy Issues A. Immediate and Long-Term Care —— fm rt Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Steinbrook, Robert, MD; Lo, Bernard, MD; Moulton, Jeffrey, PhD; Saika, Glenn, MA; Hollander, Harry, MD; Volberding, Paul A., MD. Preferences of Homosexual Men with AIDS for Life-Sustaining Treatment. The New England Journal of Medicine, 13 February 1986, Vol. 314, No. 7: 457-460. University of California, San Francisco; San Francisco General Hospital, San Francisco, California. This study examined whether AIDS patients would choose life-sustaining treatment, such as mechanical breathing support and cardiopulmonary resuscitation, and whether they would give instructions in advance to guide their care should they become mentally incompetent during their illness. Seventy-eight percent of the patients had thought a lot or a moderate amount about what care they would want if they had Pneumocystis carinii pneumonia. Ninety-five percent of the patients wanted hospitalization and antibiotic treatment, 55% wanted admission to the intensive care unit and mechanical breathing support, and 46% wanted cardiopulmonary resuscitation. Nine percent of patients had changed their minds about whether they wanted life-sustaining treatment, and 22% had changed their minds about designating substitute decision makers. Patients had ambivalent but generally positive reactions to discussing life-sustaining treatment. Although 73% of patients wanted to discuss life-sustaining treatment, only one-third had done so. Two-thirds of the patients had provided instructions to guide care if they became mentally incompetent; but only 28% had properly transferred power of attorney for health care. Patients tended to overestimate the effectiveness of life-sustaining treatment, even though they were well educated and lived in a city where their illness is widely publicized. The authors suggest that physicians who care for patients with AIDS and other serious chronic illnesses should take an active role in educating them about life-sustaining treatment and inviting them to provide instructions for future care. Patients completed a 15-minute self-administered, multiple-choice questionnaire about their preferences about life-sustaining treatment. The questionnaire also asked for demographic information and medical history and about social-psychological supports and attitudes. Information about each patient's age, diagnoses, date of diagnosis of AIDS, and previous hospitalizations was collected from medical records. Differences between groups of patients were analyzed statistically. Questionnaires were completed by 118 male AIDS patients, 112 from San Francisco General Hospital and 6 from the University of California, San Francisco, between January and May 1985. The majority of the patients were young, well educated, and severely ill. Most of their friends and parents knew they were homosexual. 1) Related Policy Issues: Intermediate and Long-Term Care (VIA) 6A-Ste-1 VI. Related Policy Issues B. Health Care Cost, Financing, and Payment Author(s): Titles Source: Institution: Findings: Scitovsky, Anne A., MA; Cline, Mary; Lee, Philip R., MD. Medical Care Costs of Patients with AIDS in San Francisco. Journal of the American Medical Association, 12 December 1986, Vol. 256, No. 22: 3103-3106. Palo Alto Medical Foundation/Research Institute, Palo Alto, California (Scitovsky, Cline); Institute for Health Policy Studies, University of California, San Francisco, California. To obtain more specific and detailed data on the costs of treating patients with AIDS, a retrospective study of the medical care costs of AIDS patients treated at San Francisco General Hospital (SFGH) during 1984 was begun in late 1984. The mean charge per AIDS hospital admission was $9,024, the mean charge per day was $773, and the mean length of stay was 11.7 days. Of the total mean charge, 92.9% was for hospital services and only 7.1% was for inpatient professional services. Charges for the hospital room accounted for almost half and laboratory tests for about one-fourth of all charges. Patients who lived for all 12 months of 1984 had mean charges of $7,026, while patients who died during 1984 had considerably higher costs ($23,425), despite having expenses for an average of only 6.4 months of 1984. Those who lived all 12 months averaged 4.8 days in the hospital, and 57% of this group had no hospital admissions. Patients who died in 1984 averaged 25.8 days in the hospital, and all but 3 of 83 patients in this group had one or more hospital stays. The majority of patients who lived all 12 months suffered from Kaposi's sarcoma, a condition that can be treated largely on an outpatient basis. Patients who were newly diagnosed in 1984 and did not die in 1984 averaged charges of $12,040 in 4.6 months. The lifetime inpatient costs of patients who died in 1984 and had all services from diagnosis to death at SFGH averaged $27,571 in charges, 34.7 hospital days, and 3.2 hospital admissions over a period of 224 days (7.5 months) from diagnosis of AIDS to death. This study found considerably lower costs for treating AIDS patients than had been estimated previously. The differences may be due to the lower number of hospital days (35 versus 168) from diagnosis to death, the shorter survival time (7.5 months versus 13.1 months), the larger number of Kaposi's sarcoma cases, the number of volunteer organizations in San Francisco's well-organized gay community which provide support services and take the burden off hospitals, and other factors. The authors stress two peints. Although there is no doubt that AIDS is a costly disease, first, the costs of treating patients can be reduced substantially with community support services that help keep patients out of the hospital as long as medically possible. Second, when comparing lifetime medical care costs of AIDS patients with lifetime costs of other diseases which are spread out over a longer period of time, such as end-stage renal disease, the costs come out about equal. What aggravates the problem of AIDS medical expenses, however, is that patients are concentrated in a few areas which must bear a very heavy burden for their treatment. 6B-Sci-1 Method: Sample Size: Policy Keys: Admissions for AIDS were identified by scanning case abstract records at SFGH for diagnostic classifications used for AIDS. Patients who had received all their inpatient and outpatient services at SFGH in 1984 were identified by the outpatient AIDS ward. A list of AIDS-related deaths was also provided. Once patients eligible for the study had been identified, all pertinent billing data were obtained from the patient accounts department. The cost data presented were based on charges. This may be a low estimate of professional services, because some services were provided at no charge or at a lower fee when patients had no insurance or insufficient funds to pay. At most these figures should be increased 15% to 20%. Charges for non-hospital-based services, such as nursing home, home health, and hospice care, counseling, outpatient drugs, acupuncture, and biofeedback, are not included. Data were collected on three types of patients with AIDS: (1) all AIDS admissions to SFGH in 1984 (445 cases); (2) patients with AIDS who received all their hospital and inpatient and outpatient professional services at SFGH in 1984 (201 cases); and (3) patients who died in 1984 who had all their hospital and inpatient professional services from diagnosis to death at SFGH (85 cases). In 1984, SFGH treated one-half of all San Francisco AIDS patients. 1) Related Policy Issues: Health Care Cost (VIB) Author(s): Title: Source: Institution: Findings: Method: Seage, George R., Ill, MPH; Landers, Stewart, JD; Barry, M. Anita, MD; Groopman, Jerome, MD; Lamb, George A., MD; Epstein, Arnold M., MD, MA. Medical Care Costs of AIDS in Massachusetts. Journal of the American Medical Association, 12 December 1986, Vol. 256, No. 22: 3107-3109. Community Infectious Disease Epidemiology Program, Division of Community Medicine, Boston Department of Health and Hospitals, and Epidemiology and Statistics Section, Boston University School of Public Health, Boston Massachusetts (Seage, Landers, Barry, Lamb); Division of Hematology and Oncology, New England Deaconess Hospital, Boston, Massachusetts (Groopman); Department of Medicine, Division of General Medicine, Brigham and Women's Hospital, Harvard Medical School and Institute for Health Research, a joint program of Harvard Community Health Plan and Harvard University, Boston, Massachusetts (Epstein). To evaluate the use and cost of medical services for patients with AIDS in Massachusetts, a l-year cost-of-illness study of 45 AIDS patients was performed. During the observation period, which averaged 7.5 months per patient, the mean number of hospitalizations per patient was 1.6, with a mean length of stay per hospitalization of 21 days, including a mean of 1 day spent in the intensive care unit. This resulted in a mean cost of $14,189 per hospitalization. The majority of inpatient expenditures were related to room, laboratory, and pharmacy. Due to the variable length of follow-up, an annualized estimate was calculated. The mean number of hospitalizations per year was estimated to be 3.3, with a total of 61.9 hospital days and 4.0 intensive care unit days. Overall, medical costs averaged $46,505 per patient per year, with 91% of these expenditures related to use of inpatient services. A greater number of opportunistic infections was correlated with higher costs due to a greater number of hospitalizations. Assuming a mean life expectancy of 13 months after diagnosis of AIDS, each patient will incur an average of $50,380 in health expenditures. For the 24,000 AIDS patients already diagnosed in the U.S., this results in an expenditure of $1.2 billion. The economic burden presents a particular problem for teaching and public hospitals. Approximately one-third of the patients in this study lacked private insurance coverage. These results are in contrast to previous estimates of $147,000 per AIDS patient for the first 10,000 cases diagnosed in the U.S. The number of hospital days used in this study was much lower (61.9 days rather than 167 days), and the estimate of resource use was based on costs rather than charges. This study was a 1-year incidence-based cost-of-illness evaluation of the health care use of a cross-section of AIDS patients. Sociodemographic data and clinical characteristics were obtained by reviewing ambulatory- care and hospital records at New England Deaconess Hospital. Outpatient medical records were also included. Information on the use of inpatient hospital services was obtained from the hospital billing department. Charges were converted to costs according to the 6B-Sea-2 Sample Size: Policy Keys: charge/cost ratio obtained from the Massachusetts Rate-Setting Commission. The study period varied from 1 to 12 months for each patient, depending on the date of diagnosis and the survival of each patient. Therefore, cost per patient and cost per year are both presented. Although this hospital was probably the major source of care for the patients in this study, some patients may have received additional care at other sites which would not be included in this analysis. Forty-five individuals, all of whom met the Centers for Disease Control criteria for AIDS and were diagnosed and alive as of | September 1984, were included. This group constituted 31% of the AIDS patients living in Massachusetts at the time and all AIDS patients cared for at the New England Deaconess Hospital at the time. Almost all of the patients (42, 93%) were homosexual or bisexual men. One was an intravenous drug abuser, one was a hemophiliac, and one had no identified risk factors. 1) Related Policy Issues: Health Care Costs (VIB) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Hardy, Ann M., DPH; Rauch, Kathryn; Echenberg, Dean, MD, PhD; Morgan, W. Meade, PhD; Curran, James W., MD, MPH. The Economic Impact of the First 10,000 Cases of Acquired Immunodeficiency Syndrome in the United States. Journal of the American Medical Association 10 January 1986, Vol. 255, No. 2: 209-211. AIDS Branch, Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia (Hardy, Morgan, Curran, Rauch); Bureau of Communicable Disease Control, San Francisco Department of Public Health, San Francisco, California (Echenberg, Rauch). The first 10,000 patients with AIDS are estimated to require more than 1.6 million hospital days, resulting in over $1.4 billion in expenditures for hospital care alone. The authors estimate that approximately $147,000 is being expended for the hospital care of each patient with AIDS. A total of 8,387 years of work will be lost from disability, at a loss of $189 million in potential earnings. The economic loss from future earnings lost following premature death of these 10,000 patients will be $4.6 billion. Although there is considerable regional variation in both mode and cost of treatment, expenditures for hospitalization and the income lost due to disability and premature death were estimated to total $6.3 billion for the first 10,000 cases of AIDS in the U.S. Estimates were calculated by extrapolation from separate surveys conducted in New York, Philadelphia, San Francisco, and Atlanta. These data were combined with national data and aggregated for three areas-- expenditures for hospitalizations, resources lost due to disability, and resources lost due to premature death. Hospital expenditures were calculated from the estimated number of hospital days and the estimated average daily hospital charge to patients with AIDS, obtained from surveys in each city, and weighted for patient origin by Centers for Disease Control (CDC) surveillance data to derive national estimates. Disability losses were estimated by applying the observed New York City disability rate 3 months before follow-up or death (86%) across the board to all patients with AIDS for the period from diagnosis to death. Work years lost were calculated for patients 15 years and older, taking into account 1980 age- and sex-specific national employment rates. Cost of years of work lost was derived by multiplying the years lost by the 1980 age- and sex-specific annual earnings. To quantify the cost to society of AIDS-related deaths, 1980 age- and sex- specific figures for expected lifetime earnings were used at a discount rate of 4% to convert future earnings into their present value. Since the mortality rate for patients 2 years after diagnosis of AIDS approaches 100%, the cost was calculated for all 10,000 patients. Estimates of the economic impact of the first 10,000 reported cases of AIDS are based on CDC surveillance data and data from New York City, Philadelphia, San Francisco, and Atlanta for three components: 6B-Har-3 expenditures for hospitalizations, resources lost due to disability, and resources lost due to premature mortality. Policy Keys: 1) Related Policy Issues: Health Care Cost (VIB) VII. Related Scientific Issues A. Animal Models for Retroviral Infections and Diseases Author(s): Title: Source: Institution: Findings: Method: Fultz, Patricia N.; McClure, Harold M.; Daugharty, Harry; Brodie, Anne; McGrath, Cornelia R.; Swenson, Brent; Francis, Donald P. Vaginal Transmission of Human Immunodeficiency Virus (HIV) to a Chimpanzee. The Journal of Infectious Diseases, November 1986, Vol. 154, No. 5: 896- 900. AIDS Program and the Division of Host Factors, Centers for Disease Control; Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia. Two female chimpanzees were exposed to human immunodeficiency virus (HIV) and monitored for evidence of seroconversion and development of AIDS symptoms. A sterile cotton-tipped swab soaked in a high- concentration preparation of lymphadenopathy-associated virus type 1 (LAV-1) was used to apply virus to the two chimpanzees--one to the vaginal mucosa and one to the oral mucosa. Two weeks after infection the virus was isolated from the vaginally exposed chimpanzee, called C- 550. No infectious virus was detected in her saliva, however. Three weeks after exposure, antibodies specific to LAV-1 were first detected in serum samples by enzyme-linked immunosorbent assay (ELISA). C-550 showed no signs of clinical disease in the first 6 months after exposure, but gained no weight during the second 6-month period. Indicators of C- 550's immunologic status, the number of lymphocytes and the helper/suppressor T-cell ratio, fluctuated in and out of the normal range as early as | week after infection. After oral exposure to virus, chimpanzee C-534 did not develop antibodies specific to LAV-1, nor was virus isolated from her blood. A second dose of LAV-1 was applied in the same manner when no signs of infection were seen within 3 months of the first application. At 5.5 months after the second application, C-534 still had no detectable virus or antibodies specific to LAV-1. Also, no virus was detected in the saliva collected by throat swabs | month after the first application and 2 weeks after the second. She showed no clinical signs of disease and no immunologic abnormalities. That no trauma was inflicted on the vaginal mucosa during application of the virus to C-550 and no blood contamination of the swab was visible after its removal from the vagina suggest that direct contact with blood is not a necessary first event in HIV infection. Two chimpanzees were exposed to LAV-1 by application directly to the vaginal mucosa of one chimpanzee and to the oral mucosa of the second chimpanzee. Blood was obtained from both chimpanzees 1, 2, 3, 5, 7, and 9 weeks after exposure and then at monthly intervals for 9 months. Both 7A-Ful-1 Sample Size: Policy Keys: chimpanzees were given physical examinations, and both were housed together in an isolation facility throughout the experiment. Two 6-year-old premenarche female chimpanzees, C-550 and C-534, born and raised at the Yerkes Regional Primate Research Center in Atlanta, Georgia, were used. Before exposure to the virus, both were seronegative for HIV antibody as determined by ELISA. 1) Related Scientific Issues: Animal Models (VIIA), 2) Transmission through Vaginal Mucosa (IIG), 3) Non-transmission through Oral Mucosa (IIG), 4) Incubation Period and Disease Progression (Chimpanzees) (IIIC, 5) Other Characteristics of Disease: HTLV-III in Saliva (IIIF) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kanki, P.J.; Alroy, J.; Essex, M. Isolation of T-Lymphotropic Retrovirus Related to HTLV-III/LAV from Wild-Caught African Green Monkeys. Science, 22 November 1985, Vol. 230: 951-954. Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts (Kanki, Essex); Department of Pathology, Tufts University School of Medicine and Veterinary Medicine, Boston, Massachusetts (Alroy). Present evidence suggests that AIDS first emerged in central Africa. The etiologic agent, human T-cell lymphotropic virus type III (HTLV-III), has been proposed to originate from recent simian-human transmission in Africa. This report describes the isolation of a retrovirus closely related to HTLV-III, designated simian T-cell lymphotropic virus (STLV-III), from 7 healthy wild-caught African green monkeys. Major proteins were similar and cross-reactive with the analogous antigens of HTLV-II. Twenty-seven of 67 monkeys tested (40%) were STLV-III positive. The use of serologic markers in the detection of infected monkeys may be important in assuring the continued safety of a variety of biologic reagents (test substances) that are derived from these primate species. The existence of a retrovirus closely related to HTLV-III that naturally infects an African nonhuman primate without apparent disease may provide a unique model for the study of human AIDS and for the development of an effective vaccine. Serum samples from 67 healthy wild-caught African green monkeys were analyzed for STLV-III antibodies. Peripheral blood lymphocytes from eight different antibody-positive monkeys were cocultivated with HUT- 78 cells, a mature human T-cell line. Cell cultures were successfully established for seven of these eight monkeys. A cytopathic effect was observed after 7 to 28 days in HUT-78 cell cultures established successfully from seven of eight monkeys. A group of 67 healthy wild-caught African green monkeys was studied. 1) Related Scientific Issues: Animal Models (VIIA) 7A-Kan-2 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Tsai, Che-Chung, DVM, PhD; Warner, Thomas F.C.S., MD, MRCPath; Uno, Hideo, MD, PhD; Giddens, W. Ellis, Jr., DVM, PhD; Ochs, Hans D., MD. Subcutaneous Fibromatosis Associated with an Acquired Immune Deficiency Syndrome in Pig-Tailed Macaques. American Journal of Pathology, July 1985, Vol. 120, No. 1: 30-37. Regional Primate Research Centers and Schools of Medicine, University of Washington, Seattle, Washington; University of Wisconsin, Madison, Wisconsin. Subcutaneous fibromatosis (SF), a nodular proliferation of vascular and fibrous tissue in the subcutaneous tissue (connective tissue just beneath the skin), was first noticed in macaque monkeys with simian acquired immunodeficiency syndrome (SAIDS) at the Washington Regional Primate Research Center (WRPRC) in 1982. This study documented this disorder in six macaques between January 1982 and June 1984. The tumors and lesions of these monkeys were found to be very similar to Kaposi's sarcoma in human AIDS. Only two of the six monkeys were still alive when the study was written up; both had lesions. Lesions consisted of a proliferation of vascular fibrous tissue infiltrated by lymphocytes and plasma cells. Clinical features included weight loss (5 of 6), diarrhea (all), lymphadenopathy (5 of 6), neutropenia (3 of 6), anemia (4 of 6), and occasional respiratory infections (all). Peripheral lymph nodes were hyperplastic, and there was splenomegaly. Aggregates of lymphocytes were present in the bone marrow, kidneys, liver, and lungs. It is not known whether AIDS or SAIDS is directly involved in the genesis of either SF or Kaposi's sarcoma. Routine microbiologic, hematologic, and immunological studies were performed in the clinical lab at WRPRC. Clinical chemical studies were performed at the University of Washington Hospital or at Eastern Washington State Hospital. Blood sera for immunoglobulin and complement (C3) level determinations were collected at biopsy from two monkeys and determined by radioimmunodiffusion. Responsiveness of peripheral blood lymphocytes of two affected monkeys and two age- and sex-matched control monkeys was assayed with concanavalin A, pokeweed mitogen, and phytohemagglutinin. Six pig-tailed macaques with SAIDS (three males, three females), all born in the WRPRC, were studied; age at diagnosis of SF ranged from 2.6 to 6.4 years. 1) Related Scientific Issues: Animal Models (VIIA) 7A-Tsa-3 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kanki, P.J.; McLane, M.F.; King, N.W., Jr.; Letvin, N.L.; Hunt, R.D.; Sehgal, P.; Daniel, M.D.; Desrosiers, R.C.; Essex, M. Serologic Identification and Characterization of a Macaque T- Lymphotropic Retrovirus Closely Related to HTLV-III. Science, 7 June 1985, Vol. 228: 1199-1201. Department of Cancer Biology, Harvard School of Public Health, Boston (Kanki, McLane, Essex); New England Regional Primate Research Center, Southborough, Massachusetts (Kanki, King, Letvin, Hunt, Sehgal, Daniel, Desrosiers) This study serologically characterized a new simian retrovirus simian T- cell lymphotropic virus type III (STLV-III), related to human T-cell lymphotropic virus type III (HTLV-II) which naturally infects a nonhuman primate species to gain further understanding about the etiology and pathobiology of AIDS. Serologic characterization revealed STLV-III- specific proteins of 160, 120, 55, and 24 kilodaltons, similar in size to the major gag and env proteins of HTLV-IIl. Antigens were recognized by representative macaque serum samples and human reference serum samples positive for HTLV-III antibodies. Monoclonal antibodies directed to p24, the major core protein of HTLV-II, also immunoprecipitated a 24-kilodalton species in lysates of cells infected with STLV-IIIL. All seven inoculated macaques, which were previously free of disease, succumbed to a variety of opportunistic infections, with clinical signs and pathological lesions similar to those observed in spontaneous immune deficiency disease of macaques. Blood sera obtained from representative sick macaques at the New England Regional Primate Research Center in Southborough, Massa- chusetts, were compared with human reference serum positive for HTLV- [II. Serologic testing with radioimmunoprecipitation analysis was used to identify and characterize the virus, STLV-III, as being similar to the human AIDS virus (HTLV-II). Tumor cells and cell-free preparations were obtained from an STLV-III-infected macaque and used to inoculate seven healthy rhesus macaques. Four representative human and macaque sera that were positive for HTLV-II proteins or STLV-IIl proteins or both were screened for antibodies. Seven healthy rhesus monkeys were inoculated. | 1) Related Scientific Issues: Animal Models (VIIA) 7A-Kan-4 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Budzko, Delia B.; Madden, David L.; London, William T.; Sever, John L. Immunologic Alterations in Monkeys with Simian Acquired Immunodeficiency Syndrome (SAIDS). Proceedings of the Society for Experimental Biology and Medicine, 1985, Vol. 179: 227-231. Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. In this study simian acquired immunodeficiency syndrome (SAIDS) was used as a model for human AIDS; healthy monkeys were inoculated with the SAIDS virus and monitored. All four inoculated monkeys developed lymphadenopathy, splenomegaly, leukopenia, and neutropenia 2 to 4 weeks after inoculation. Leukocytes at that time constituted 25% to 30% of total white cells (a low-normal value). Leukocyte numbers in three monkeys returned to normal levels 6 to 8 weeks after inoculation. One monkey developed progressive SAIDS (lymphadenopathy, splenomegaly, Kaposi's sarcoma-like abdominal lesions, severe neutropenia, anemia, and severe weight loss due to diarrhea); this monkey died 5.5 weeks after inoculation. This monkey also had significantly lower levels of la-positive cells 4 weeks after infection; it showed progressively suppressed responses to a range of specific mitogens. The three surviving infected monkeys had impaired responses to the T- cell-specific mitogens concanavalin A, phytohemagglutinin, pokeweed mitogen (PWM), Staphylococcus aureus and to the T-cell-dependent B- cell stimulant PWM 4 to 6 weeks after infection; responses improved and reached near normal levels within 12 to 18 weeks. There was no significant change in the percentage of Tll-bearing cells in any study animal. The helper/suppressor T-cell ratio did not vary significantly in any of the animals. Results indicate that evidence of immunosuppression due to SAIDS appears within a few weeks after infection, affects both T cells and B cells, and may progress in animals that eventually die. In this laboratory study, healthy monkeys were injected with 0.9 ml of a pool of filtered plasma samples from terminally ill monkeys with experimentally transmitted SAIDS. Four rhesus monkeys were inoculated, and four healthy monkeys were used as a control group. All were monitored for 18 weeks. Tests were performed for lymphocyte responsiveness to B- and T-cell-specific mitogens and to detect la, T4, T8, and T11 antigens on peripheral blood mononuclear cells. Four normal 3-year-old rhesus macaques (short-tailed monkeys), each weighing 3 kg and reared at the Infectious Diseases Branch of the National Institute of Neurological and Communicative Disorders and Stroke, were injected with plasma from monkeys terminally ill with SAIDS. Four uninfected control monkeys were also studied. 7A-Bud-5 Policy Keys: 1) Related Scientific Issues: Animal Models (VIIA), 2) Disease Stages (IIIC) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Maul, Donald H.; Miller, Claramae H.; Marx, Preston A.; Bleviss, Mara L.; Madden, David L.; Henrickson, Roy V.; Gardner, Murray B. Immune Defects in Simian Acquired Immunodeficiency Syndrome. Veterinary Immunology and Immunopathology, 1985, Vol. 8: 201-214. California Primate Research Center and the School of Medicine, Department of Pathology, University of California, Davis, California (Maul, Miller, Marx, Bleviss, Henrickson, Gardner); Infectious Diseases Branch Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (Madden). This study investigated immune defects in monkeys with experimentally and naturally transmitted simian acquired immunodeficiency syndrome (SAIDS). Monkeys who developed clinical signs of SAIDS but without opportunistic infections 2 to 6 weeks after inoculation were categorized as early SAIDS. Those categorized as having terminal SAIDS had severe disease with opportunistic infections, which developed either spontaneously or after experimental inoculation. All terminal SAIDS monkeys died between | day and 4 weeks after immune studies were done. Both early and terminal SAIDS monkeys had significantly depressed responses to all mitogens tested; in terminal SAIDS, these became more severely depressed near death. Interleukin 2 (IL-2) caused complete or partial restoration of response to the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). Concentrations of immunoglobulin G (IgG) and immunoglobulin M (IgM) were significantly decreased. The helper/suppressor T-cell ratio was not significantly different than for controls in either early or terminal SAIDS monkeys, but the percentages and absolute cell counts of early and terminal SAIDS monkeys were lower than for the controls. For both early and terminal SAIDS monkeys, IgG and IgM declined through the course of disease, complement component C3 was unchanged, and C4 increased slightly. Both the humoral and cell mediated immune response rates are affected in SAIDS. The authors encourage further study of the role of IL-2 in this immune defect. This laboratory study tested lymphocyte responses to the mitogens Con A, PHA and pokeweed mitogen with and without IL-2. Immunoglobulin (IgG and IgM) and complement (C3 and C4) concentrations were determined by radial immunodiffusion. Helper and suppressor T cells were identified with monoclonal antibodies OKT4 and OKTS, respectively. Immune studies were done at early or terminal stages of SAIDS. For each set of tests, monkeys of both sexes, aged 9 to 18 months and weighing 1.5 to 3.5 kg, were used. All monkeys were born at the California Primate Research Center. A control of one healthy rhesus monkey of comparable age and sex was used in each test. Clinical evaluations (physical exams, complete blood counts, and serum chemistry profiles) were performed to confirm that each monkey was healthy before inoculation. 7A-Mau-6 Policy Keys: 1) Related Scientific Issues: Animal Models (VIIA), 2) Immunological Aspects (IIIE), 3) Disease Stages (IIIC) Author(s): Title: Status: Institution: Findings: Method: Alter, Harvey J.; Eichberg, Jorg W.; Masur, Henry; Saxinger, W. Carl; Gallo, Robert C.; Macher, Abe M.; Lane, H. Clifford; Fauci, Anthony S. Transmission of HTLV-II Infection from Human Plasma to Chimpanzees: An Animal Model for AIDS. Published: Science, 2 November 1984, Vol. 226: 549-552. Blood Bank Department, Clinical Center, National Institutes of Health, Bethesda, Maryland (Alter); Virology and Immunology Department, Southwest Foundation for Biomedical Research, San Antonio, Texas (Eichberg); Critical Care Medicine Department, Clinical Center, National Institutes of Health (Masur); Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland (Saxinger, Gallo); Laboratory of Pathology, National Cancer Institute (Macher); Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (Lane, Fauci);. This study focused on the potential for transmission of human AIDS to healthy chimpanzees. Two of three chimpanzees given plasma from human AIDS or pre-AIDS patients showed serum antibodies to human T- cell lymphotropic virus type III (HTLV-II) 10 to 12 weeks after infection. No opportunistic infections occurred. One chimp also devel- oped lymphadenopathy, transient depression in the helper/suppressor T- cell ratio, and impaired in vitro blastogenic responses (in blastogenesis, small lymphocytes from peripheral blood are transformed into large nucleated blood cells). In both seropositive animals, lymph node enlargement persisted for 32 weeks and antibody to HTLV-III persisted for at least 48 weeks. The untreated control chimp remained healthy. These results indicate that chimpanzees are susceptible to HTLV-III and can develop a clinical syndrome of lymphadenopathy and immunological impairment that simulates AIDS-related lymphadenopathy, indicating that the chimpanzee is a good infectivity model for AIDS study. The results also confirm that lymphocyte-poor plasma and plasma derivatives, such as clotting-factor concentrates used in treating hemophilia, can transmit HTLV-III to recipients. In this laboratory study, three chimps were injected with 50 to 150 ml of plasma from three AIDS patients, one of whom had lymphadenopathy, one of whom had Kaposi's sarcoma, and one of whom had opportunistic infections. The chimps were given biweekly physical exams; immunologic tests included biweekly lymphocyte counts, number of T3, T4, and T8 cells; number of B cells, natural killer cell activity, and lymphocyte mitogen responsiveness. An enzyme-linked immunosorbent TA-Alt-7 Sample Size: Policy Keys: assay was used to determine antibodies to HTLV-IIl. A healthy chimp used as a control was given plasma from three healthy donors. Four healthy chimpanzees were studied; three were injected with plasma from AIDS patients and one, used as a control, was injected with plasma from healthy donors. 1) Related Scientific Issues: Animal Models (VIIA), 2) Transmission: Blood Products (IIC) Author(s): Title: Source: Institution: Findings: Method: Marx, Preston A.; Maul, Donald H.; Osborn, Kent G.; Lerche, Nicholas W.; Moody, Peggy; Lowenstine, Linda J.; Henrickson, Roy V.; Arthur, Larry O.; Gilden, Raymond V.; Gravell, Maneth; London, William T.; Sever, John L.; Levy, Jay A.; Munn, Robert J.; Gardner, Murray B. Simian AIDS: Isolation of a Type D Retrovirus and Transmission of the Disease. Science, 9 March 1984, Vol. 223: 1083-1086. California Primate Research Center, University of California, Davis, California (Marx, Maul, Osborn, Lerche, Moody, Lowenstine, Henrickson); Frederick Cancer Research Facility, Frederick, Maryland (Arthur, Gilden); Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland (Gravell, London, Sever); Cancer Research Institute, University of California Medical Center, San Francisco, California (Levy); Department of Pathology, School of Medicine, University of California, Davis, California (Munn, Gardner). Simian AIDS (SAIDS), which occurs endemically in colonies of macaque monkeys in the U.S., resembles AIDS in humans in overall clinical manifestations, pathology and immune deficiency. A new type D retrovirus, related to but distinct from Mason-Pfizer monkey virus, was isolated in the laboratory from the blood of two rhesus monkeys infected with SAIDS. Three juvenile rhesus monkeys that were injected intravenously with tissue culture fluids containing this virus developed SAIDS after 2 to 4 weeks. Results indicate that a type D retrovirus appears to be an etiologic agent of SAIDS in monkeys at the California Primate Research Center (CPRC). This simian model could prove useful for determining how an infectious retrovirus depletes lymphoid cells, to develop measures for controlling SAIDS in primates. Tissue from a 3-year-old monkey with naturally occurring SAIDS was injected into a healthy rhesus monkey; the injected monkey developed SAIDS 4 months later. A blood sample from the inoculated monkey was injected into two l2-month-old monkeys, and into rhesus monkey kidney cells. Both 12-month-old monkeys were sick 60 to 65 days after inoculation, with SAIDS symptoms of lymphadenopathy, splenomegaly (enlarged spleen), neutropenia, diarrhea, weight loss, and lymphoid depletion. Cells from the infected kidney cell culture were transferred in vitro three times, and portions were prepared for electron microscopy and hemadsorption assays. When examined by electron microscope, the culture had particles resembling type D retroviruses ranging in size from 110 to 130 nm and occasional budding particles (precursors of type D retrovirus). Uninfected monkey kidney cells showed no virus particles. This type D retrovirus was compared with Mason-Pfizer monkey virus and found to have similar features. Another portion of the infected kidney cell culture was injected into an 18-month-old monkey, which developed neutropenia, lymphadenopathy, 7A-Mar-8 Sample Size: Policy Keys: and splenomegaly after 16 days, and was close to death at 52 days. Two monkeys injected with comparable amounts of uninfected monkey kidney cell culture were healthy 5 months after inoculation. To confirm the results, another portion of the infected culture was injected into two healthy monkeys and produced SAIDS within 16 days; both monkeys were alive 8 weeks after inoculation. Subjects were female rhesus monkeys at the California Primate Research Center, aged 12 months to 3 years. 1) Related Scientific Issues: Animal Models (VIIA), 2) Related Scientific Issues: New Virus Subtypes (VIIB) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Gravell, Maneth; London, William T.; Houff, Sidney A.; Madden, David L.; Daiakas, Marinos C.; Sever, John L.; Osborn, Kent G.; Maul, Donald H.; Henrickson, Roy V.; Marx, Preston A.; Lerche, Nicholas W.; Prahalada, Srinivasa; Gardner, Murray B. Transmission of Simian Acquired Immunodeficiency Syndrome (SAIDS) with Blood or Filtered Plasma. Science, 6 January 1984, Vol. 223, No. 4631: 74-76. Infectious Diseases Branch, National Institute for Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (Gravell, London, Houff, Madden, Dalakas, Sever); California Primate Research Center, University of California, Davis, California (Osborn, Maul, Henrickson, Marx, Lerche, Prahalada); Depart- ment of Pathology, School of Medicine, University of California, Davis, California (Gardner). This laboratory study of simian acquired immunodeficiency syndrome (SAIDS) transmission with filtered plasma was conducted on four healthy rhesus monkeys in an attempt to characterize the SAIDS agent. All four recipients developed SAIDS 2 to 4 weeks after inoculation. Three monkeys died 5 to 9 weeks after inoculation. Monkeys 5 and 6 were negative for antibody to rhesus monkey cytomegalovirus (CMV); monkeys 7 and 8 had antibody to rhesus monkey CMV. Monkey 8 remains alive with persistent generalized lymphadenopathy and splenomegaly 3 months after inoculation. A characteristic feature of all monkeys that died (including those in a similar previous experiment) was lymphoid depletion of lymph node cortices, splenic white pulp, and thymic cortex. Immunoblasts were sparse and plasma cells were virtually absent. No SAIDS-infected monkey had an inverted helper/suppressor T-cell ratio, a major difference from AIDS patients. The small filter size used for the blood plasma suggests that the causative agent is small and probably a virus. However, no virus was isolated by standard techniques from the blood or filtered plasma that caused SAIDS. In this laboratory study, four healthy juvenile rhesus monkeys were inoculated with 3 ml of filtered plasma from two moribund donor rhesus monkeys infected with experimentally transmitted SAIDS. The donor plasma was filtered sequentially through two Millipore filters of 0.45-um pore size. Also determined were mitogen stimulation response, helper/suppressor T-cell ratio, and immunoglobulin concentrations. Four healthy juvenile rhesus monkeys and two moribund donor rhesus monkeys with experimentally transmitted SAIDS were studied. Monkeys 5 and 6 (both female, ages ll and 8 months) were inoculated at the National Institutes of Health, and monkeys 7 and 8 (both male, age 14 months) were inoculated at the California Primate Research Center. Monkeys 1 through 4 were used in a previous study. 1) Related Scientific Issues: Animal Models (VIIA) 7A-Gra-9 Author(s): Title: Source: Institution: Findings: Method: Sample: Policy Keys: Osborn, Kent G., DVM; Prahalada, Srinivasa, BVSc, PhD; Lowenstine, Linda J., DVM, PhD; Gardner, Murray B., MD; Maul, Don H., DVM; Henrickson, Roy V., DVM. The Pathology of an Epizootic of Acquired Immunodeficiency in Rhesus Macaques. American Journal of Pathology, January 1984, Vol. 114, No. 1: 94-103. California Primate Research Center, Departments of Pathology, Schools of Veterinary Medicine and Medicine, University of California, Davis, California. A syndrome of apparent AIDS within a colony of rhesus macaques with unusually high mortality was identified at the California Primate Research Center. The cause of death for most of the affected animals included septicemia (systemic disease caused by microorganisms in the blood) and/or chronic diarrhea with wasting, often complicated by other infectious agents. In many cases, multiple or unusual infectious agents were Isolated or recognized, including cytomegalovirus, and Candida albicans. Two animals developed cutaneous fibrosarcomas (malignant tumors of connective tissue in the skin). Affected animals had generalized lymphadenopathy and enlargement of the spleen, with depletion of T-cell populations. This spontaneous disease syndrome in nonhuman primates had similarities to AIDS in humans. This may provide a potential animal model for the study of the complex factors modulating the immune system. Clinical and autopsy reports for all animals housed in this outdoor California primate colony from 1981 to 1984 were examined and compared. Standard autopsy procedures were used. In addition, the most recently dead animals were subjected to more detailed postmortem examination. Biopsies from living animals were also examined, including skin lesions from one animal now dead, lymph nodes from five animals (three still living), and a subcutaneous tissue mass from one animal that is still living. The group consisted of 56 animals introduced into the enclosure in August 1981 and eight animals retained from a previous group housed in the same enclosure, as well as 13 births. Of six males, two were imported wild animals. The other four males and 49 females were colony-born. Twenty-nine animals from this colony were presented for autopsy since the group was formed. 1) Related Scientific Issues: Animal Models of AIDS (VIIA) 7A-0sb-10 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Chalifoux, Laura V.; King, Norval W.; Letvin, Norman L. Morphologic Changes in Lymph Nodes of Macaques with an Immunodeficiency Syndrome. Laboratory Investigation, 1984, Vol. 51, No. 1: 22-26. New England Regional Primate Research Center, Southborough, Massachusetts; Dana-Farber Cancer Institute, Boston, Massachusetts. In a study of structural lymph node changes in macaque monkeys with immunodeficiencies, results indicate that morphologic abnormalities evolve over time in an orderly sequence of changes. In early disease stages, there was marked follicular hyperplasia and a reduced paracortex, primarily of suppressor T cells. In more advanced stages, lymph nodes showed follicular involution (return to normal size) and loss of B cells. Lymph nodes in terminal stages showed a total effacement of architecture, with a marked depletion of lymphocytes. These findings are remarkably similar to changes in humans with AIDS, and they underline the importance of studying this disease in macaques as a model for studying human AIDS. In this laboratory study, lymph nodes from macaque monkeys were examined by electron microscopy and both routine histologic and immunoperoxidase staining techniques, using monoclonal antibodies that recognize specific primate lymphocyte subsets. Eight sequential biopsies of groin or armpit lymph nodes were done on three monkeys before death; an average of 25 lymph nodes from 6 to ll sites were obtained at autopsy from all four monkeys. Three macaque monkeys with spontaneously occurring macaque immunodeficiency syndrome were studied, along with one macaque monkey with experimentally transmitted immunodeficiency syndrome induced by inoculation of macaque lymphoma tissue. (This procedure was reported in the paper N.L. Letvin et al., The Lancet, 1983, 1i:599.) 1) Related Scientific Issues: Animal Models (VIIA), 2) Immunological Aspects (IIE) 7A-Cha-11 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Letvin, Norman L.; Eaton, Kathryn A.; Aldrich, Wayne R.; Sehgal, Prabhat K.; Blake, Beverly J.; Schlossman, Stuart F.; King, Norval W.; Hunt, Ronald D. Acquired Immunodeficiency Syndrome in a Colony of Macaque Monkeys. Proceedings of the National Academy of Science, May 1983, Vol. 80, No. 9: 2718-2722. New England Regional Primate Research Center, Southborough, Massachusetts (Letvin, Eaton, Aldrich, Sehgal, Blake, King, Hunt); Division of Tumor Immunology, Sidney Farber Cancer Institute, Boston, Massachusetts (Letvin, Schlossman). This study documented a naturally occurring immunodeficiency syndrome in a captive colony of macaque monkeys at the New England Regional Primate Research Center (NERPRC), primarily in the species Macaca cyclopis. The mortality rate for M. cyclopis in 1978 was 8% (7 of 87); in 1979 it was 13.3% (11 of 83); in 1980 it was 33.3% (24 of 71); and in 1981 it was 29% (18 of 62). Mortality rates for these years for all monkey species (including M. cyclopis) at NERPRC were 11.9%, 12.9%, 18%, and 13.9%, respectively. A review of 1981 and 1980 autopsy records revealed that a significant number of M. cyclopis animals that had died had a similar hematologic profile: anemia, neutropenia, and monocytosis (diminished number of monocytes, large white blood cells, in the circulating blood). Liver function tests suggested hepatitis. A similar hematologic profile emerged for the species Macaca mulatta (which had not had significant increases in deaths during 1978-81). In a cohort of 15 monkeys that died in 1981 (13 M. cyclopis and two M. mulatta), primary causes of death were lymphomas or opportunistic infections such as Pneumocystis carinii pneumonia and noma (gangrenous condition of oral mucous membranes). Pokeweed mitogen, concanvalin A, and xenogeneic (foreign DNA) cell- stimulated responses by lymphocytes of diseased monkeys were dramatically diminished. The helper/suppressor T-cell ratios in the peri- pheral blood of the diseased M. cyclopis monkeys were decreased compared with either M. mulatta monkeys in the same colony or normal humans. The similarity of this syndrome to human AIDS indicates that it may provide an important model for studying AIDS. Routine hematologic studies were done at a clinical lab at the NERPRC. Serum chemistry studies were done at a nearby commercial lab. A retrospective study of colony autopsy records confirmed the increase in M. cyclopis deaths. (Detailed records are maintained for each animal and autopsies are performed on all animals that die at the NERPRC.) The NERPRC breeds and maintains a colony of 1,200 primates of 14 different species, housed in both indoor and outdoor individual and gang cages. The NERPRC maintains 780 monkeys of the genus Macaca, comprising mostly the species Macaca mulatta (rhesus), Macaca 7A-Let-12 fascicularis (crab-eating monkey), and Macaca cyclopis (Formosan or Taiwanese rock macaque). Policy Keys: 1) Related Scientific Issues: Animal Models (VIIA) Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Henrickson, Roy V.; Osborn, Kent G.; Madden, David L.; Anderson, John H.; Maul, Donald H.; Sever, John L.; Ellingsworth, Larry R.; Lowenstine, Linda J.; Gardner, Murray B. Epidemic of Acquired Immunodeficiency in Rhesus Monkeys. The Lancet, 19 February 1983, Vol. 1, No. 8321: 388-390. California Primate Research Center, University of California, Davis; Infectious Diseases Branch, Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; Department of Medical Pathology, University of California, Davis, California. In the 15 months since a colony of 64 rhesus monkeys was established, 24 animals have died of an AIDS-like syndrome, a mortality rate of 37.5%. Age- and sex-matched mortality among controls for the same period was 5.5%. All 24 animals that died were female, including 22 juveniles (0.5 to 3.5 years) and 2 adults (older than 3.5 years). Peak mortality occurred 6 months after introduction into the cage. Affected animals showed abnormal cellular immune functions. The syndrome was characterized by fever, generalized lymphadenopathy, splenomegaly, diarrhea, severe opportunistic infections including cytomegalovirus, chronic wasting, and high mortality. The authors suggest that the syndrome observed in this outbreak may provide an animal model for human AIDS. Sequential blood samples were taken during the course of the illness, and complete blood counts were routinely performed. A variety of immuno- logical tests were conducted on serum collected before entry into the cage and during acute and terminal phases of the illness. Complete autopsies were performed on all 24 animals that died or were killed during the final stages of illness. Clinical and laboratory findings were presented. The sample was a group of 64 rhesus monkeys in one outdoor cage, including 9 apparently healthy females from a previous group in which several members were diagnosed with apparent acquired immunodeficiency. Of the six males in the group, two had been caught wild and imported; the other four males and 58 females were colony- born. Most animals were under 3 years of age. Controls included 558 healthy rhesus monkeys with a 15:1 ratio of females to males, held in six adjacent cages. 1) Related Scientific Issues: Animal Models of AIDS (VIIA) 7A-Hen-13 Ce -l VII. Related Scientific Issues B. New Virus Subtypes Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Kanki, Phyllis J.; Barin, Francis; M'Boup, Souleyman; Allan, Jonathan S.; Romet-Lemonne, Jean Loup; Marlink, Richard; McLane, Mary Frances; Lee, Tun-Hou; Arbeille, Brigitte; Denis, Francois; Essex, M. New Human T-Lymphotropic Retrovirus Related to Simian T- Lymphotropic Virus Type III (STLV-II 5 pg) Science, 11 April 1986, Vol. 232: 238-243. Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts (Kanki, Allan, Romet-Lemonne, Marlink, McLane, Lee, Essex); Virology Laboratory, CHRU Bretonneau and UER Pharmaceutical Sciences, Tours, France (Barin); Bacteriology-Virology Laboratory, Dakar University, Dakar, Senegal (M'Boup); Electron Microscopy Unit, CHRU Bretonneau, Tours, France (Arbeille); CHRU Dupuyfren, Limoges, France (Denis). This report describes evidence of human T-cell lymphotropic virus type IV (HTLV-IV), a new human T-cell lymphotropic virus similar to simian T- cell lymphotropic virus type II (STLV-III), which affects African green monkeys. HTLV-IV affects apparently healthy people in Senegal, West Africa. Serum samples from apparently healthy West Africans were tested with antigens of HTLV type IlI/lymphadenopathy-associated virus (HTLV- [II[/LAV). These samples reacted strongly with all the viral antigens of STLV-IIl, but showed minimal or no reactivity with HTLV-III/LAV. HTLV-IV had retrovirus-type particles and growth characteristics, and major viral proteins similar to those of the STLV-IIl and HTLV-III/LAV group of retroviruses. These data suggest that HTLV-IV has more structural components in common with STLV-III than with the HTLV- [II/LAV group of viruses that infect people in the U.S. and Europe. The authors theorize that STLV-III or HTLV-IV may have been the progenitor of the human AIDS virus and that further study of STLV-III may expand understanding of the origins of AIDS. Serum samples were tested by radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by enzyme-linked immunosorbent assay. HTLV-IV was isolated from the West African patients and grown in test tubes. Sera from 23 Americans (AIDS patients, AIDS-related complex patients, and healthy male homosexuals), 16 Africans from Dakar, Senegal, and 12 wild-caught African green monkeys were studied. 1) Related Scientific Issues: New Virus Subtypes (VIIB), 2) Geographic Trends: West Africa (IB5), 3) Related Scientific Issues: Animal Models (VIIA) 7B-Kan-1 Author(s): Title: Source: Institution: Findings: Method: Sample Size: Policy Keys: Barin, F; Denis, F.; Allan, J.S.; M'Boup, S.; Kanki, P.; Lee, T.H.; and Essex, M. Serological Evidence for Virus Related to Simian T-Lymphotropic Retrovirus III In Residents of West Africa. The Lancet, 21/28 December 1985, Vol. 2, No. 8469/70: 1387-1389. Virology Laboratory, CHRU Bretonneau and UER Pharmaceutical Sci- ences, Tours, France; Bacteriology-Virology Laboratory, Dakar University, Dakar, Senegal; CHU Dupuytren, Limoges, France; Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts. This study considers the possibility that certain African populations may have been exposed to viruses closely related to simian T-cell lymphotropic virus type III (STLV-III). Evidence is presented that a virus closely related to STLV-III infects humans in Senegal, West Africa, a region where AIDS and AIDS-related disease have not yet been observed. Blood sera from 20 of 289 prostitutes and 5 of 122 surgical patients that were positive for antibodies for human TLV-III (HTLV-II) by enzyme-linked immunosorbent assay (ELISA) were examined for antibodies to HTLV-II and STLV-III by Western blot. Sera from individuals originating from regions where AIDS has been reported, such as the United States and Burundi (central Africa) reacted best with antigens of HTLV-III, although antibodies that cross-reacted with STLV- [Il protein 24 were also detected. Conversely, sera originating from Senegalese people reacted better with STLV-III than with HTLV-III. In this seroepidemiological study, blood sera were screened for antibodies to HTLV-III by an ELISA, and positive sera were then tested for antibodies to HTLV-III proteins and STLV-III proteins by Western blot. A group of 289 prostitutes appearing periodically at a clinic for sexually transmitted diseases in Dakar, Senegal, was considered a high-risk group. A group of 122 surgical inpatients with no symptoms of AIDS or AIDS-related complex were studied as a nonrisk population. 1) Related Scientific Issues: STLV-III (VIIB,A), 2) Geographic Trends: West Africa (Senegal) (IB5), 3) Populations: Heterosexuals (Prostitutes) (IA6) 7B-Bar-2 Acquired Immunodeficiency Syndrome AIDS Recommendations and Guidelines November 1982 - November 1986 Centers for Disease Control Atlanta, Georgia 30333 PUBLIC HEALTH SERVICE DEPARTMENT OF HEALTH AND HUMAN SERVICES P=-1 TABLE OF CONTENTS GENERAL RECOMMENDATIONS & GUIDELINES Prevention of acquired immune deficiency syndrome (AIDS): Report of inter-agency recommendations. MMWR 1983 Mar4;32:101-03 ..............oiiiiiiiiiiniinnn 1 Recommendations for preventing transmission of infection with human T-lymphotropic virus type lll/lymphadenopathy-associated virus in the workplace. MMWR 1985 Nov 15;34:881-B8,691-98 unison ssn ivssnadsss wuss seins seins» ¥eees i oe% ei sma: 3 ' Additional recommendations to reduce sexual and drug abuse-related transmission of human T-lymphotropic virus type lll/lymphadenopathy-associated virus. MMWR 1986 Mar 14;35:152-55 11 HEALTH-CARE WORKERS AND LABORATORY PERSONNEL Acquired immunodeficiency syndrome (AIDS): Precautions for clinical and laboratory staffs. MMWR 1982 NOV IB i31IBT TBO! ... . swiw vv xcmn £3 500s 5a os Swee s 5 54g 2&3 15 Acquired immunodeficiency syndrome (AIDS): Precautions for health-care workers and allied professionals. MMWR 1983 Sept 2;32:450-51 ............................. 17 Recommendations for preventing possible transmission of human T-lymphotropic virus type lll/lymphadenopathy-associated virus from tears. MMWR 1985 Aug 30,34: BBB-BA ....ovincioninnmvsinmisssmmvssbmisisshn iii Sum TEE Ciampi Rs diaaWiTs om 18 Recommendations for preventing transmission of infection with human T-lymphotropic virus type lll/lymphadenopathy-associated virus during invasive procedures. MMWR 1986 ADF LVi3B220=2B ov niin 505 50.00 wi wet» od Wo 0 8 0 0 6 0, 8 5 etn 20 Recommended infection-control practices for dentistry MMWR 1986 Apr 18; SB 2T-BT cin 55 rm on wv TD § FE © + irae 4 rss vege A a 21 Human T-lymphotropic virus type lll/lymphadenopathy-associated virus: Agent summary statement. MMWR 1986 Aug 29;35:540-42,547-49 . . ........................... 25 HEMOPHILIA PATIENTS Update: Acquired immunodeficiency syndrome (AIDS) in persons with hemophilia. MMWR 1884106 268533 BBD-0 v.00 55 00000 5.8.05 ivr om 5m 04h 50 5 BIBER or HE BEA HE BIDE E i 31 . PATIENTS WITH SPECIAL DISEASE CONDITIONS Recommendations for providing dialysis treatment to patients infected with human T- lymphotropic virus type |ll/lymphadenopathy-associated virus. MMWR 1986 June 13:38:78 78.38T vv eonniiesemmns img sweme ss sume seen § 4 § Ene ne wnn ob www sw 33 Diagnosis and management of mycobacterial infection and disease in persons with human T-lymphotropic virus type lll/lymphadenopathy-associated virus infection. MMWR 1986 July 18;35:448-52 37 . DONORS OF BODY FLUIDS AND TISSUES Provisional Public Health Service inter-agency recommendations for screeniing donated blood and plasma for antibody to the virus causing acquired immunodeficiency syndrome. MMWR 1985 Jan 11,38: 128 .cuvsvnininsn roses ssamss sss inseam s saemsss $e 41 Testing donors of organs, tissues, and semen for antibody to human T-lymphotropic virus type lll/lymphadenopathy-associated virus MMWR 1985 May 24;34:294 . ........ .. 4d Update: Revised Public’ Health Service definition of persons who should refrain from donating blood and plasma — United States. MMWR 1985 Sept 6,34:547-48 ...... a4 Vi. VII. VIL CONTENTS VACCINES Hepatitis B vaccine: Evidence confirming lack of AIDS transmission. MMWR 1984 Dec YB:BBBBBaBT iv oiis ss mms owners bamess bine swine men bs bel 8808S Le hing sone 47 Safety of therapeutic immune globulin preparations with respect to transmission of human T-lymphotropic virus type lll/lymphadenopathy-associated virus infection. MMWR 1986 APE VVIBBIRB YTB 00015 rev wisn ces ms SFist GET wows om ns ee gt Ty is mms ws wm 503: 0. 48 Immunization of children infected with human T-lymphotropic virus type lll/lymphadenopathy-associated virus. MMWR 1986 Sept 26;35:595-598, BOBOB cc oinitmii ni 36 aims» wrwimin 0 SEGA #8 HA £85 vorwsin wo 0 rome 3 § 900 8 3 8 (501.8 # 0 vomit 4 30 cis 3 § (0 5 50 MATERNAL AND CHILD HEALTH Education and foster care of children infected with human T-lymphotropic virus type Il/lymphadenopathy-associated virus. MMWR 1985 Aug 30;34:517-21 Recommendations for assisting in the prevention of perinatal transmission of human T- lymphotropic virus type lll/lymphadenopathy-associated virus and acquired immunodefi- ciency syndrome. MMWR 1985 Dec 6;34:721-26,731-32 ........................ 58 WORLD HEALTH ORGANIZATION GUIDELINES World Health Organization workshop: Conclusions and recommendations on acquired im- munodeficiency syndrome (AIDS). MMWR 1985 May 17;34:275-76 ............... 65 P-3 I. GENERAL RECOMMENDATIONS & GUIDELINES 1983 Mar 4,32:101-03 Prevention of Acquired Immune Deficiency Syndrome (AIDS): Report of Inter-Agency Recommendations Since June 1981, over 1,200 cases of acquired immune deficiency syndrome (AIDS) have been reported to CDC from 34 states, the District of Columbia, and 15 countries. Reported cases of AIDS include persons with Kaposi's sarcoma who are under age 60 years and/or per- sons with life-threatening opportunistic infections with no known underlying cause for immune deficiency. Over 450 persons have died from AIDS, and the case-fatality rate ex- ceeds 60% for cases first diagnosed over 1 year previously (7,2). Reports have gradually in- creased in number. An average of one case per day was reported during 1981, compared with three to four daily in late 1982 and early 1983. Current epidemiologic evidence identifies several groups in the United States at increased risk for developing AIDS (3-7). Most cases have been reported among homosexual men with multiple sexual partners, abusers of intrave- nous (IV) drugs, and Haitians, especially those who have entered the country within the past few years. However, each group contains many persons who probably have little risk of ac- quiring. AIDS. Recently, 11 cases of unexplained, life-threatening opportunistic infections and cellular immune deficiency have been diagnosed in patients with hemophilia. Available data suggest that the severe disorder of immune regulation underlying AIDS is caused by a trans- missible agent. A national case-control study and an investigation of a cluster of cases among homosexual men in California indicate that AIDS may be sexually transmitted among homosexual or bisexual men (8,9). AIDS cases were recently reported among women who were steady sexual partners of men with AIDS or of men in high-risk groups, suggesting the possibility of heterosexual transmission (70). Recent reports of unexplained cellular immunodeficiencies and opportunistic infections in infants born to mothers from groups at high risk for AIDS have raised concerns about in utero or perinatal transmission of AIDS (77). Very little is known about risk factors for Haitians with AIDS. The distribution of AIDS cases parallels that of hepatitis B virus infection, which is trans- mitted sexually and parenterally. Blood products or blood appear responsible for AIDS among hemophilia patients who require clotting factor replacement. The likelihood of blood transmis- sion is supported by the occurrence of AIDS among IV drug abusers. Many drug abusers share contaminated needles, exposing themselves to blood-borne agents, such as hepatitis B virus. Recently, an infant developed severe immune deficiency and an opportunistic infection several months after receiving a transfusion of platelets derived from the blood of a man sub- sequently found to have AIDS (72). The possibility of acquiring AIDS through blood compo- nents or blood is further suggested by several cases in persons with no known risk factors who have received blood products or blood within 3 years of AIDS diagnosis (2). These cases are currently under investigation. No AIDS cases have been documented among health care or laboratory personnel caring for AIDS patients or processing laboratory specimens. To date, no person-to-person transmis- sion has been identified other than through intimate contact or blood transfusion. Several factors indicate that individuals at risk for transmitting AIDS may be difficult to identify. A New York City study showed that a significant proportion of homosexual men who were asymptomatic or who had nonspecific symptoms or signs (such as generalized lympha- denopathy) had altered immune functions demonstrated by in vitro tests (2,73,74). Similar findings have been reported among patients with hemophilia (2,75, 76). Although the signifi- cance of these immunologic alterations is not yet clear, their occurrence in at least two groups at high risk for AIDS suggests that the pool of persons potentially capable of transmit- ting an AIDS agent may be considerably larger than the presently known number of AIDS cases. Furthermore, the California cluster investigation and other epidemiologic findings sug- gest a “latent period” of several months to 2 years between exposure and recognizable clini- cal illness and imply that transmissibility may precede recognizable illness. Thus, careful histo- ries and physical examinations alone will not identify all persons capable of transmitting AIDS but should be useful in identifying persons with definite AIDS diagnoses or related symptoms, P-4 such as generalized lymphadenopathy, unexplained weight loss, and thrush. Since only a small percentage of members of high-risk groups actually has AIDS, a laboratory test is clearly needed to identify those with AIDS or those at highest risk of acquiring AIDS. For the above reasons, persons who may be considered at increased risk of AIDS include those with symp- toms and signs suggestive of AIDS; sexual partners of AIDS patients; sexually active homo- sexual or bisexual men with multiple partners; Haitian entrants to the United States; present or past abusers of IV drugs; patients with hemophilia; and sexual partners of individuals at in- creased risk for AIDS. Statements on prevention and control of AIDS have been issued by the National Gay Task Force, the National Hemophilia Foundation, the American Red Cross, the American Associa- tion of Blood Banks, the Council of Community Blood Centers, the American Association of Physicians for Human Rights, and others. These groups agree that steps should be imple- mented to reduce the potential risk of transmitting AIDS through blood products, but differ in the methods proposed to accomplish this goal. Public health agencies, community organiza- tions, and medical organizations and groups share the responsibility to rapidly disseminate in- formation on AIDS and recommended precautions. Although the cause of AIDS remains unknown, the Public Health Service recommends the following actions: 1. Sexual contact should be avoided with persons known or suspected to have AIDS. Members of high risk groups should be aware that multiple sexual partners increase the probability of developing AIDS. 2. As a temporary measure, members of groups at increased risk for AIDS should refrain from donating plasma and/or blood. This recommendation includes all individuals be- longing to such groups, even though many individuals are at little risk-of AIDS. Centers collecting plasma and/or blood should inform potential donors of this recommendation. The Food and Drug Administration (FDA) is preparing new recommendations for manu- facturers of plasma derivatives and for establishments collecting plasma or blood. This is an interim measure to protect recipients of blood products and blood until specific laboratory tests are available. 3. Studies should be conducted to evaluate screening procedures for their effectiveness in identifying and excluding plasma and blood with a high probability of transmitting AIDS. These procedures should include specific laboratory tests as well as careful histo- ries and physical examinations. 4. Physicians should adhere strictly to medical indications for transfusions, and autolo- gous blood transfusions are encouraged. 5. Work should continue toward development of safer blood products for use by hemophilia patients. The National Hemophilia Foundation has made specific recommendations for management of patients with hemophilia (7 7). The interim recommendation requesting that high-risk persons refrain from donating plasma and/or blood is especially important for donors whose plasma is recovered from plas- mapheresis centers or other sources and pooled to make products that are not inactivated and may transmit infections, such as hepatitis B. The clear intent of this recommendation is to eliminate plasma and blood potentially containing the putative AIDS agent from the supply. Since no specific test is known to detect AIDS at an early stage in a potential donor, the recommendation to discourage donation must encompass all members of groups at increased risk for AIDS, even though it includes many individuals who may be at little risk of transmitting AIDS. As long as the cause remains unknown, the ability to understand the natural history of AIDS and to undertake preventive measures is somewhat compromised. However, the above recommendations are prudent measures that should reduce the risk of acquiring and transmit- ting AIDS. Reported by the Centers for Disease Control, the Food and Drug Administration, and the National Insti- tutes of Health. References 1. CDC. Update on acquired immune deficiency syndrome (AIDS)—United States. MMWR 1982;31:507-8,513-4. 2. CDC. Unpublished data. 3. CDC. Update on Kaposi's sarcoma and opportunistic infections in previously health persons — United States. MMWR 1982;31:294, 300-1. 4. CDC. Opportunistic infections and Kaposi's sarcoma among Haitians in the United States. MMWR 1982;31:353-4, 360-1. 5. CDC. Pneumocystis cariniipneumonia among persons with hemophilia A. MMWR 1982,31:365-7 6. CDC. Update on acquired immune deficiency syndrome (AIDS) among patients with hemophilia A MMWR 1982,31.644-6, 652. 7. Vieira J, Frank E, Spira TJ, Landesman SH. Acquired immune deficiency in Haitians: opportunistic in- fections in previously healthy Haitian immigrants. N Engl J Med 1983,308:125-9. 8 CDC. Unpublished data. 9. CDC. A cluster of Kaposi's sarcoma and Pneumocystis carinii pneumonia among homosexual male residents of Los Angeles and Orange Counties, California. MMWR 1982,31 305-7 10. CDC. Immunodeficiency among female sexual partners of males with acquired immune deficiency syndrome (AIDS) —New York. MMWR 1983,31:697-8 11. CDC. Unexplained immunodeficiency and opportunistic infections in infants —New York, New Jersey, California. MMWR 1982,;31:665-7 12. CDC. Possible transfusion-associated acquired immune deficiency syndrome (AIDS) — California MMWR 1982,31:652-4 13. CDC Persistent, generalized lymphadenopathy among homosexual males MMWR 1982.31:249-51. 14. Kornfeld H, Vande Stouwe RA, Lange M, Reddy MM, Grieco MH. T-lymphocyte subpopulations in homosexual men. N Engl J Med 1982;307:729-31. 15. Lederman MM, Ratnoff OD, Scillian JJ, Jones PK, Schacter B. Impaired cell-mediated immunity in patients with classic hemophilia. N Engl J Med 1983,308:79-83 16. Menitove JE, Aster RH, Casper JT, et al. T-lymphocyte subpopulations in patients with classic hemophilia treated with cryoprecipitate and lyophilized concentrates. N Engl J Med 1983,308:83-6 17. Medical and Scientific Advisory Council. Recommendations to prevent AIDS in patients with hemophilia. New York: National Hemophilia Foundation, January 14, 1983. 1985 Nov 15;34:681—86, 691-95 Recommendations for Preventing Transmission of Infection with Human T-Lymphotropic Virus Type lll/ Lymphadenopathy-Associated Virus in the Workplace Summary: The information and recommendations contained in this document have been developed with particular emphasis on health-care workers and others in related occupations in which exposure might occur to blood from persons infected with HTLV-III/LAV, the “AIDS virus.” Because of public concern about the purported risk of transmission of HTLV-III/LAV by per- sons providing personal services and those preparing and serving food and beverages, this document also addresses personal-service and food-service workers. Finally, it addresses “other workers” — persons in settings, such as offices, schools, factories, and construction sites, where there is no known risk of AIDS virus transmission. Because AIDS is a bloodborne, sexually transmitted disease that is not spread by casual contact, this document does not recommend routine HTLV-III/LAV antibody screening for the groups addressed. Because AIDS is not transmitted through preparation or serving of food and beverages, these recommendations state that food-service workers known to be infected with AIDS should not be restricted from work unless they have another infection or illness for which such restriction would be warranted. This document contains detailed recommendations for precautions appropriate to prevent transmission of all bloodborne infectious diseases to people exposed —in the course of their duties—to blood from persons who may be infected with HTLV-III/LAV. They emphasize that health-care workers should take all possible precautions to prevent needlestick injury. The recommendations are based on the well-documented modes of HTLV-II/LAV transmission and incorporate a “worst case” scenario, the hepatitis B model of transmission. Because the hepatitis B virus is also bloodborne and is both hardier and more infectious than HTLV-lII/LAV, recommendations that would prevent transmission of hepatitis B will also prevent transmis- sion of AIDS. Formulation of specific recommendations for health-care workers who perform invasive procedures is in progress. Persons at increased risk of acquiring infection with human T-lymphotropic virus type IIl/lymphadenopathy-associated virus (HTLV-III/LAV), the virus that causes acquired immuno- deficiency syndrome (AIDS), include homosexual and bisexual men, intravenous (IV) drug abusers, persons transfused with contaminated blood or blood products, heterosexual con- tacts of persons with HTLV-III/LAV infection, and children born to infected mothers. HTLV-IIl/ LAV is transmitted through sexual contact, parenteral exposure to infected blood or blood components, and perinatal transmission from mother to neonate. HTLV-III/LAV has been P-6 isolated from blood, semen, saliva, tears, breast milk, and urine and is likely to be isolated from some other body fluids, secretions, and excretions, but epidemiologic evidence has im- plicated only blood and semen in transmission. Studies of nonsexual household contacts of AIDS patients indicate that casual contact with saliva and tears does not result in transmission of infection. Spread of infection to household contacts of infected persons has not been detected when the household contacts have not been sex partners or have not been infants of infected mothers. The kind of nonsexual person-to-person contact that generally occurs among workers and clients or consumers in the workplace does not pose a risk for transmis- sion of HTLV-III/LAV. As in the development of any such recommendations, the paramount consideration is the protection of the public's health. The following recommendations have been developed for all workers, particularly workers in occupations in which exposure might occur to blood from indi- viduals infected with HTLV-II/LAV. These recommendations reinforce and supplement the specific recommendations that were published earlier for clinical and laboratory staffs (7) and for dental-care personnel and persons performing necropsies and morticians’ services (2). Because of public concern about the purported risk of transmission of HTLV-III/LAV by persons providing personal services and by food and beverages, these recommendations contain infor- mation and recommendations for personal-service and food-service workers. Finally, these recommendations address workplaces in general where there is no known risk of transmission of HTLV-II/LAV (e.g., offices, schools, factories, construction sites). Formulation of specific recommendations for health-care workers (HCWs) who perform invasive procedures (e.g., sur- geons, dentists) is in progress. Separate recommendations are also being developed to prevent HTLV-III/LAV transmission in prisons, other correctional facilities, and institutions housing indi- viduals who may exhibit uncontrollable behavior (e.g., custodial institutions) and in the perinatal setting. In addition, separate recommendations have already been developed for children in schools and day-care centers (3). HTLV-lII/LAV-infected individuals include those with AIDS (4); those diagnosed by their physician(s) as having other illnesses due to infection with HTLV-III/LAV; and those who have virologic or serologic evidence of infection with HTLV-III/LAV but who are not ill. These recommendations are based on the well-documented modes of HTLV-III/LAV trans- mission identified in epidemiologic studies and on comparison with the hepatitis B experience. Other recommendations are based on the hepatitis B model of transmission. COMPARISON WITH THE HEPATITIS B VIRUS EXPERIENCE The epidemiology of HTLV-III/LAV infection is similar to that of hepatitis B virus (HBV) infec- tion, and much that has been learned over the last 15 years related to the risk of acquiring hepatitis B in the workplace can be applied to understanding the risk of HTLV-III/LAV transmis- sion in the health-care and other occupational settings. Both viruses are transmitted through sexual contact, parenteral exposure to contaminated blood or blood products, and perinatal transmission from infected mothers to their offspring. Thus, some of the same major groups at high risk for HBV infection (e.g., homosexual men, IV drug abusers, persons with hemophilia, in- fants born to infected mothers) are also the groups at highest risk for HTLV-III/LAV infection. Neither HBV nor HTLV-III/LAV has been shown to be transmitted by casual contact in the work- place, contaminated food or water, or airborne or fecal-oral routes (5). HBV infection is an occupational risk for HCWs, but this risk is related to degree of contact with blood or contaminated needles. HCWs who do not have contact with blood or needles contaminated with blood are not at risk for acquiring HBV infection in the workplace (6-8). In the health-care setting, HBV transmission has not been documented between hospital- ized patients, except in hemodialysis units, where blood contamination of the environment has been extensive or where HBV-positive blood from one patient has been transferred to another patient through contamination of instruments. Evidence of HBV transmission from HCWs to patients has been rare and limited to situations in which the HCWs exhibited high concentra- tions of virus in their blood (at least 100,000,000 infectious virus particles per ml of serum), and the HCWs sustained a puncture wound while performing traumatic procedures on patients or had exudative or weeping lesions that allowed virus to contaminate instruments or open wounds of patients (9-77). Current evidence indicates that, despite epidemiologic similarities of HBV and HTLV-IlI/ LAV infection, the risk for HBV transmission in health-care settings far exceeds that for HTLV-III/LAV transmission. The risk of acquiring HBV infection following a needlestick from an HBV carrier ranges from 6% to 30% (72,73), far in excess of the risk of HTLV-IIlI/LAV infec- tion following a needlestick involving a source patient infected with HTLV-III/LAV, which is less than 1%. In addition, all HCWs who have been shown to transmit HBV infection in health- care settings have belonged to the subset of chronic HBV carriers who, when tested, have ex- r-7 hibited evidence of exceptionally high concentrations of virus (at least 100,000,000 infec- tious virus particles per ml) in their blood. Chronic carriers who have substantially lower con- centrations of virus in their blood have not been implicated in transmission in the health-care setting (9-77,74). The HBV model thus represents a “worst case” condition in regard to transmission in health-care and other related settings. Therefore, recommendations for the control of HBV infection should, if followed, also effectively prevent spread of HTLV-III/LAV. Whether additional measures are indicated for those HCWs who perform invasive procedures will be addressed in the recommendations currently being developed. Routine screening of all patients or HCWs for evidence of HBV infection has never been recommended. Control of HBV transmission in the health-care setting has emphasized the implementation of recommendations for the appropriate handling of blood, other body fluids, and items soiled with blood or other body fluids. TRANSMISSION FROM PATIENTS TO HEALTH-CARE WORKERS HCWs include, but are not limited to, nurses, physicians, dentists and other dental workers, optometrists, podiatrists, chiropractors, laboratory and blood bank technologists and techni- cians, phlebotomists, dialysis personnel, paramedics, emergency medical technicians, medical examiners, morticians, housekeepers, laundry workers, and others whose work involves con- tact with patients, their blood or other body fluids, or corpses. Recommendations for HCWs emphasize precautions appropriate for preventing transmis- sion of bloodborne infectious diseases, including HTLV-III/LAV and HBV infections. Thus, these precautions should be enforced routinely, as should other standard infection-control precautions, regardless of whether HCWs or patients are known to be infected with HTLV-IIl/ LAV or HBV. In addition to being informed of these precautions, all HCWs, including students and housestaff, should be educated regarding the epidemiology, modes of transmission, and prevention of HTLV-III/LAV infection. Risk of HCWs acquiring HTLV-III/LAV in the workplace. Using the HBV model, the high- est risk for transmission of HTLV-III/LAV in the workplace would involve parenteral exposure to a needle or other sharp instrument contaminated with blood of an infected patient. The risk to HCWs of acquiring HTLV-III/LAV infection in the workplace has been evaluated in several studies. In five separate studies, a total of 1,498 HCWs have been tested for antibody to HTLV-III/LAV. In these studies, 666 (44.5%) of the HCWs had direct parenteral (needlestick or cut) or mucous membrane exposure to patients with AIDS or HTLV-III/LAV infection. Most of these exposures were to blood rather than to other body fluids. None of the HCWs whose ini- tial serologic tests were negative developed subsequent evidence of HTLV-III/LAV infection following their exposures. Twenty-six HCWs in these five studies were seropositive when first tested; all but three of these persons belonged to groups recognized to be at increased risk for AIDS (75). Since one was tested anonymously, epidemiologic information was availa- ble on only two of these three seropositive HCWSs. Although these two HCWs were reported as probable occupationally related HTLV-III/LAV infection (75,76), neither had a preexposure nor an early postexposure serum sample available to help determine the onset of infection. One case reported from England describes a nurse who seroconverted following an accidental parenteral exposure to a needle contaminated with blood from an AIDS patient (7 7). In spite of the extremely low risk of transmission of HTLV-III/LAV infection, even when needlestick injuries occur, more emphasis must be given to precautions targeted to prevent needlestick injuries in HCWs caring for any patient, since such injuries continue to occur even during the care of patients who are known to be infected with HTLV-IlI/LAV. Precautions to prevent acquisition of HTLV-III/LAV infection by HCWs in the work- place. These precautions represent prudent practices that apply to preventing transmission of HTLV-III/LAV and other bloodborne infections and should be used routinely (78). 1. Sharp items (needles, scalpel blades, and other sharp instruments) should be consid- ered as potentially infective and be haridled with extraordinary care to prevent acciden- tal injuries. 2. Disposable syringes and needles, scalpel blades, and other sharp items should be placed into puncture-resistant containers located as close as practical to the area in which they were used. To prevent needlestick injuries, needles should not be recapped, purposefully bent, broken, removed from disposable syringes, or otherwise manipulated by hand. 3. When the possibility of exposure to blood or other body fluids exists, routinely recom- mended precautions should be followed. The anticipated exposure may require gloves alone, as in handling items soiled with blood or equipment contaminated with blood or other body fluids, or may also require gowns, masks, and eye-coverings when perform- ing procedures involving more extensive contact with blood or potentially infective P-8 body fluids, as in some dental or endoscopic procedures or postmortem examinations. Hands should be washed thoroughly and immediately if they accidentally become con- taminated with blood. 4. To minimize the need for emergency mouth-to-mouth resuscitation, mouth pieces, resuscitation bags, or other ventilation devices should be strategically located and available for use in areas where the need for resuscitation is predictable. 5. Pregnant HCWs are not known to be at greater risk of contracting HTLV-III/LAV infec- tions than HCWs who are not pregnant; however, if a HCW develops HTLV-III/LAV in- fection during pregnancy, the infant is at increased risk of infection resulting from perinatal transmission. Because of this risk, pregnant HCWs should be especially famil- iar with precautions for the preventing HTLV-III/LAV transmission (79). Precautions for HCWs during home care of persons infected with HTLV-III/LAV. Per- sons infected with HTLV-III/LAV can be safely cared for in home environments. Studies of family members of patients infected with HTLV-IlI/LAV have found no evidence of HTLV-III/ LAV transmission to adults who were not sexual contacts of the infected patients or to children who were not at risk for perinatal transmission (3). HCWs providing home care face the same risk of transmission of infection as HCWs in hospitals and other health-care settings, especially if there are needlesticks or other parenteral or mucous membrane exposures to blood or other body fluids. When providing health-care service in the home to persons infected with HTLV-III/LAV, measures similar to those used in hospitals are appropriate. As in the hospital, needles should not be recapped, purposefully bent, broken, removed from disposable syringes, or otherwise manipulated by hand. Needles and other sharp items should be placed into puncture-resistant containers and disposed of in accordance with local regulations for solid waste. Blood and other body fluids can be flushed down the toilet. Other items for disposal that are contaminated with blood or other body fluids that cannot be flushed down the toilet should be wrapped securely in a plastic bag that is impervious and sturdy (not easily penetrated). It should be placed in a second bag before being discarded in a manner consistent with local regulations for solid waste disposal. Spills of blood or other body fluids should be cleaned with soap and water or a household detergent. As in the hospital, individuals cleaning up such spills should wear disposable gloves. A disinfectant solution or a freshly prepared solution of sodium hy- pochlorite (household bleach, see below) should be used to wipe the area after cleaning. Precautions for providers of prehospital emergency health care. Providers of prehospi- tal emergency health care include the following: paramedics, emergency medical technicians, law enforcement personnel, firefighters, lifeguards, and others whose job might require them to provide first-response medical care. The risk of transmission of infection, including HTLV- I/LAV infection, from infected persons to providers of prehospital emergency health care should be no higher than that for HCWs providing emergency care in the hospital if appropri- ate precautions are taken to prevent exposure to blood or other body fluids. Providers of prehospital emergency health care should follow the precautions outlined above for other HCWSs. No transmission of HBV infection during mouth-to-mouth resuscita- tion has been documented. However, because of the theoretical risk of salivary transmission of HTLV-III/LAV during mouth-to-mouth resuscitation, special attention should be given to the use of disposable airway equipment or resuscitation bags and the wearing of gloves when in contact with blood or other body fluids. Resuscitation equipment and devices known or sus- pected to be contaminated with blood or other body fluids should be used once and disposed of or be thoroughly cleaned and disinfected after each use. Management of parenteral and mucous membrane exposures of HCWs. If a HCW has a parenteral (e.g., needlestick or cut) or mucous membrane (e.g., splash to the eye or mouth) exposure to blood or other body fluids, the source patient should be assessed clinically and epidemiologically to determine the likelihood of HTLV-III/LAV infection. If the assessment suggests that infection may exist, the patient should be informed of the incident and request- ed to consent to serologic testing for evidence of HTLV-III/LAV infection. If the source patient has AIDS or other evidence of HTLV-III/LAV infection, declines testing, or has a positive test, the HCW should be evaluated clinically and serologically for evidence of HTLV-III/LAV infec- tion as soon as possible after the exposure, and, if seronegative, retested after 6 weeks and on a periodic basis thereafter (e.g., 3, 6, and 12 months following exposure) to determine if transmission has occurred. During this follow-up period, especially the first 6-12 weeks, when most infected persons are expected to seroconvert, exposed HCWs should receive counseling about the risk of infection and follow U.S. Public Health Service (PHS) recommen- dations for preventing transmission of AIDS (20,27). If the source patient is seronegative and has no other evidence of HTLV-III/LAV infection, no further follow-up of the HCW is neces- P-9 sary. If the source patient cannot be identified, decisions regarding appropriate follow-up should be individualized based on the type of exposure and the likelihood that the source pa- tient was infected. Serologic testing of patients. Routine serologic testing of all patients for antibody to HTLV-UI/LAV is not recommended to prevent transmission of HTLV-III/LAV infection in the workplace. Results of such testing are unlikely to further reduce the risk of transmission, which, even with documented needlesticks, is already extremely low. Furthermore, the risk of needlestick and other parenteral exposures could be reduced by emphasizing and more con- sistently implementing routinely recommended infection-control precautions (e.g., not recap- ping needles). Moreover, results of routine serologic testing would not be available for emergency cases and patients with short lengths of stay, and additional tests to determine whether a positive test was a true or false positive would be required in populations with a low prevalence of infection. However, this recommendation is based only on considerations of occupational risks and should not be construed as a recommendation against other uses of the serologic test, such as for diagnosis or to facilitate medical management of patients. Since the experience with infected patients varies substantially among hospitals (75% of all AIDS cases have been reported by only 280 of the more than 6,000 acute-care hospitals in the United States), some hospitals in certain geographic areas may deem it appropriate to initiate serologic testing of patients. TRANSMISSION FROM HEALTH-CARE WORKERS TO PATIENTS Risk of transmission of HTLV-III/LAV infection from HCWs to patients. Although there is no evidence that HCWs infected with HTLV-III/LAV have transmitted infection to patients, a risk of transmission of HTLV-III/LAV infection from HCWs to patients would exist in situations where there is both (1) a high degree of trauma to the patient that would provide a portal of entry for the virus (e.g., during invasive procedures) and (2) access of blood or serous fluid from the infected HCW to the open tissue of a patient, as could occur if the HCW sustains a needlestick or scalpel injury during an invasive procedure. HCWs known to be infected with HTLV-III/LAV who do not perform invasive procedures need not be restricted from work unless they have evidence of other infection or illness for which any HCW should be restrict- ed. Whether additional restrictions are indicated for HCWs who perform invasive procedures is currently being considered. Precautions to prevent transmission of HTLV-III/LAV infection from HCWs to pa- tients. These precautions apply to all HCWs, regardless of whether they perform invasive procedures: (1) All HCWs should wear gloves for direct contact with mucous membranes or nonintact skin of all patients and (2) HCWs who have exudative lesions or weeping dermatitis should refrain from all direct patient care and from handling patient-care equipment until the condition resolves. Management of parenteral and mucous membrane exposures of patients. If a patient has a parenteral or mucous membrane exposure to blood or other body fluids of a HCW, the patient should be informed of the incident and the same procedure outlined above for expo- sures of HCWs to patients should be followed for both the source HCW and the potentially ex- posed patient. Management of this type of exposure will be addressed in more detail in the recommendations for HCWs who perform invasive procedures. Serologic testing of HCWSs. Routine serologic testing of HCWs who do not perform inva- sive procedures (including providers of ‘home and prehospital emergency care) is not recom- mended to prevent transmission of HTLV-III/LAV infection. The risk of transmission is ex- tremely low and can be further minimized when routinely recommended infection-control pre- cautions are followed. However, serologic testing should be available to HCWs who may wish to know their HTLV-III/LAV infection status. Whether indications exist for serologic testing of HCWs who perform invasive procedures is currently being considered. Risk of occupational acquisition of other infectious diseases by HCWs infected with HTLV-III/LAV. HCWs who are known to be infected with HTLV-III/LAV and who have defec- tive immune systems are at increased risk of acquiring or experiencing serious complications of other infectious diseases. Of particular concern is the risk of severe infection following exposure to patients with infectious diseases that are easily transmitted if appropriate precau- tions are not taken (e.g., tuberculosis). HCWs infected with HTLV-III/LAV should be counseled about the potential risk associated with taking care of patients with transmissible infections and should continue to follow existing recommendations for infection control to minimize their risk of exposure to other infectious agents (78,79). The HCWSs’ personal physician(s), in conjunction with their institutions’ personnel health services or medical directors, should determine on an individual basis whether the infected HCWs can adequately and safely per- form patient-care duties and suggest changes in work assignments, if indicated. In making P-10 this determination, recommendations of the Immunization Practices Advisory Committee and institutional policies concerning requirements for vaccinating HCWs with live-virus vaccines should also be considered. STERILIZATION, DISINFECTION, HOUSEKEEPING, AND WASTE DISPOSAL TO PRE- VENT TRANSMISSION OF HTLV-III/LAV Sterilization and disinfection procedures currently recommended for use (22,23) in health- care and dental facilities are adequate to sterilize or disinfect instruments, devices, or other items contaminated with the blood or other body fluids from individuals infected with HTLV-IIl/ LAV. Instruments or other nondisposable items that enter normally sterile tissue or the vascular system or through which blood flows should be sterilized before reuse. Surgical instruments used on all patients should be decontaminated after use rather than just rinsed with water. Decontamination can be accomplished by machine or by hand cleaning by trained personnel wearing appropriate protective attire (24) and using appropriate chemical germicides. Instru- ments or other nondisposable items that touch intact mucous membranes should receive high- level disinfection. Several liquid chemical germicides commonly used in laboratories and health-care facilities have been shown to kill HTLV-III/LAV at concentrations much lower than are used in practice (25). When decontaminating instruments or medical devices, chemical germicides that are registered with and approved by the U.S. Environmental Protection Agency (EPA) as “steri- lants” can be used either for sterilization or for high-level disinfection depending on contact time; germicides that are approved for use as “hospital disinfectants” and are mycobacteri- cidal when used at appropriate dilutions can also be used for high-level disinfection of devices and instruments. Germicides that are mycobactericidal are preferred because myco- bacteria represent one of the most resistant groups of microorganisms; therefore, germicides that are effective against mycobacteria are also effective against other bacterial and viral pathogens. When chemical germicides are used, instruments or devices to be sterilized or dis- infected should be thoroughly cleaned before exposure to the germicide, and the manufactur- er's instructions for use of the germicide should be followed. Laundry and dishwashing cycles commonly used in hospitals are adequate to decontami- nate linens, dishes, glassware, and utensils. When cleaning environmental surfaces, house- keeping procedures commonly used in hospitals are adequate; surfaces exposed to blood and body fluids should be cleaned with a detergent followed by decontamination using an EPA-approved hospital disinfectant that is mycobactericidal. Individuals cleaning up such spills should wear disposable gloves. Information on specific label claims of commercial ger- micides can be obtained by writing to the Disinfectants Branch, Office of Pesticides, Environ- mental Protection Agency, 401 M Street, S.W., Washington, D.C., 20460. In addition to hospital disinfectants, a freshly prepared solution of sodium hypochlorite (household bleach) is an inexpensive and very effective germicide (25). Concentrations rang- ing from 5,000 ppm (a 1:10 dilution of household bleach) to 500 ppm (a 1:100 dilution) sodium hypochlorite are effective, depending on the amount of organic material (e.g., blood, mucus, etc.) present on the surface to be cleaned and disinfected. Sharp items should be considered as potentially infective and should be handled and dis- posed of with extraordinary care to prevent accidental injuries. Other potentially infective waste should be contained and transported in clearly identified impervious plastic bags. If the outside of the bag is contaminated with blood or other body fluids, a second outer bag should be used. Recommended practices for disposal of infective waste (23) are adequate for dis- posal of waste contaminated by HTLV-III/LAV. Blood and other body fluids may be carefully poured down a drain connected to a sanitary sewer. CONSIDERATIONS RELEVANT TO OTHER WORKERS Personal-service workers (PSWs). PSWs are defined as individuals whose occupations involve close personal contact with clients .(e.g., hairdressers, barbers, estheticians, cosme- tologists, manicurists, pedicurists, massage therapists). PSWs whose services (tattooing, ear piercing, acupuncture, etc.) require needles or other instruments that penetrate the skin should follow precautions indicated for HCWSs. Although there is no evidence of transmission of HTLV-III/LAV from clients to PSWs, from PSWs to clients, or between clients of PSWs, a risk of transmission would exist from PSWs to clients and vice versa in situations where there is both (1) trauma to one of the individuals that would provide a portal of entry for the virus and (2) access of blood or serous fluid from one infected person to the open tissue of the other, as could occur if either sustained a cut. A risk of transmission from client to client exists when instruments contaminated with blood are not sterilized or disinfected between clients. However, HBV transmission has been documented only rarely in acupuncture, ear piercing, and tattoo establishments and never in other personal-service settings, indicating that any P=11 risk for HTLV-III/LAV transmission in personal-service settings must be extremely low. All PSWs should be educated about transmission of bloodborne infections, including HTLV-III/LAV and HBV. Such education should emphasize principles of good hygiene, antisep- sis, and disinfection. This education can be accomplished by national or state professional or- ganizations, with assistance from state and local health departments, using lectures at meet- ings or self-instructional materials. Licensure requirements should include evidence of such education. Instruments that are intended to ‘penetrate the skin (e.g., tattooing and acupuncture needles, ear piercing devices) should be used once and disposed of or be thoroughly cleaned and sterilized after each use using procedures recommended for use in health-care institu- tions. Instruments not intended to penetrate the skin but which may become contaminated with blood (e.g., razors), should be used for only one client and be disposed of or thoroughly cleaned and disinfected after use using procedures recommended for use in health-care insti- tutions. Any PSW with exudative lesions or weeping dermatitis, regardless of HTLV-III/LAV in- fection status, should refrain from direct contact with clients until the condition resolves. PSWs known to be infected with HTLV-III/LAV need not be restricted from work unless they have evidence of other infections or illnesses for which any PSW should also be restricted. Routine serologic testing of PSWs for antibody to HTLV-III/LAV is not recommended to prevent transmission from PSWs to clients. Food-service workers (FSWs). FSWs are defined as individuals whose occupations in- volve the preparation or serving of food or beverages (e.g., cooks, caterers, servers, waiters, bartenders, airline attendants). All epidemiologic and laboratory evidence indicates that blood- borne and sexually transmitted infections are not transmitted during the preparation or serving of food or beverages, and no instances of HBV or HTLV-III/LAV transmission have been docu- mented in this setting. All FSWs should follow recommended standards and practices of good personal hygiene and food sanitation (26). All FSWs should exercise care to avoid injury to hands when prepar- ing food. Should such an injury occur, both aesthetic and sanitary considerations would dictate that food contaminated with blood be discarded. FSWs known to be infected with HTLV-III/ LAV need not be restricted from work unless they have evidence of other infection or illness for which any FSW should also be restricted. Routine serologic testing of FSWs for antibody to HTLV-lII/LAV is not recommended to prevent disease transmission from FSWs to consumers. Other workers sharing the same work environment. No known risk of transmission to co-workers, clients, or consumers exists from HTLV-lII/LAV-infected workers in other settings (e.g., offices, schools, factories, construction sites). This infection is spread by sexual contact with infected persons, injection of contaminated blood or blood products, and by perinatal transmission. Workers known to be infected with HTLV-III/LAV should not be restricted from work solely based on this finding. Moreover, they should not be restricted from using tele- phones, office equipment, toilets, showers, eating facilities, and water fountains. Equipment contaminated with blood or other body fluids of any worker, regardless of HTLV-III/LAV infec- tion status, should be cleaned with soap and water or a detergent. A disinfectant solution or a fresh solution of sodium hypochlorite (household bleach, see above) should be used to wipe the area after cleaning. OTHER ISSUES IN THE WORKPLACE The information and recommendations contained in this document do not address all the potential issues that may have to be considered when making specific employment decisions for persons with HTLV-III/LAV infection. The diagnosis of HTLV-III/LAV infection may evoke unwarranted fear and suspicion in some co-workers. Other issues that may be considered in- clude the need for confidentiality, applicable federal, state, or local laws governing occupa- tional safety and health, civil rights of employees, workers’ compensation laws, provisions of collective bargaining agreements, confidentiality of medical records, informed consent, em- ployee and patient privacy rights, and employee right-to-know statutes. DEVELOPMENT OF THESE RECOMMENDATIONS The information and recommendations contained in these recommendations were devel- oped and compiled by CDC and other PHS agencies in consultation with individuals represent- ing various organizations. The following organizations were represented: Association of State and Territorial Health Officials, Conference of State and Territorial Epidemiologists, Associa- tion of State and Territorial Public Health Laboratory Directors, National Association of County Health Officials, American Hospital Association, United States Conference of Local Health Officers, Association for Practitioners in Infection Control, Society of Hospital Epidemi- ologists of America, American Dental Association, American Medical Association, American Nurses’ Association, American Association of Medical Colleges, American Association of P-12 Dental Schools, National Institutes of Health, Food and Drug Administration, Food Research Institute, National Restaurant Association, National Hairdressers and Cosmetologists Associa- tion, National Gay Task Force, National Funeral Directors and Morticians Association, Ameri- can Association of Physicians for Human Rights, and National Association of Emergency Medical Technicians. The consultants also included a labor union representative, an attorney, a corporate medical director, and a pathologist. However, these recommendations may not re- flect the views of individual consultants or the organizations they represented. References 1. 2. 3 19. 20. 21. 22. 23. 24. 25. 26. CDC. Acquired immune deficiency syndrome (AIDS): precautions for clinical and laboratory staffs. MMWR 1982;31:577-80. CDC. Acquired immunodeficiency syndrome (AIDS): precautions for health-care workers and allied professionals. MMWR 1983,32:450-1. CDC. Education and foster care of children infected with human T-lymphotropic virus type lIl/ lymphadenopathy-associated virus. MMWR 1985;34:517-21. CDC. Revision of the case definition of acquired immunodeficiency syndrome for national reporting — United States. MMWR 1985;34:373-5. CDC. ACIP recommendations for protection against viral hepatitis. MMWR 1985;34:313-24, 329-335. Hadler SC, Doto IL, Maynard JE, et al. Occupational risk of hepatitis B infection in hospital workers. Infect Control 1985;6:24-31. Dienstag JL, Ryan DM. Occupational exposure to hepatitis B virus in hospital personnel: infection or immunization? Am J Epidemiol 1982;115:26-39. Pattison CP, Maynard JE, Berquist KR, et al. Epidemiology of hepatitis B in hospital personnel. Am J Epidemiol 1975,;101:59-64. Kane MA, Lettau LA. Transmission of HBV from dental personnel to patients. JADA 1985;110: 634-6. Hadler SC, Sorley DL, Acree KH, et al. An outbreak of hepatitis B in a dental practice. Ann Intern Med 1981;95:133-8. Carl M, Blakey DL, Francis DP, Maynard JE. Interruption of hepatitis B transmission by modification of a gynaecologist’s surgical technique. Lancet 1982;i:731-3. Seeff LB, Wright EC, Zimmerman HJ, et al. Type B hepatitis after needlestick exposure: prevention with hepatitis B immune globulin. Ann Intern Med 1978,88:285-93. Grady GF, Lee VA, Prince AM, et al. Hepatitis B immune globulin for accidental exposures among medical personnel: Final report of a multicenter controlled trial. J Infect Dis 1978,138:625-38. Shikata T, Karasawa T, Abe K, et al. Hepatitis B e antigen and infectivity of hepatitis B virus. J Infect Dis 1977,136:571-6. CDC. Update: evaluation of human T-lymphotropic virus type lll/lymphadenopathy-associated virus infection in health-care personnel — United States. MMWR 1985;34:575-8. Weiss SH, Saxinger WC, Rechtman D, et al. HTLV-II infection among health care workers: associa- tion with needle-stick injuries. JAMA 1985;254:2089-93. Anonymous. Needlestick transmission of HTLV-II from a patient infected in Africa. Lancet 1984.ii:1376-7. Garner JS, Simmons BP. Guideline for isolation precautions in hospitals. Infect Control 1983;4: 245-325. Williams WW. Guideline for infection control in hospital personnel. Infect Control 1983,4:326-49. CDC. Prevention of acquired immune deficiency syndrome (AIDS): report of inter-agency recom- mendations. MMWR 1983;32:101-3. CDC. Provisional Public Health Service inter-agency recommendations for screening donated blood and plasma for antibody to the virus causing acquired immunodeficiency syndrome. MMWR 1985;34:1-5. Favero MS. Sterilization, disinfection, and antisepsis in the hospital. In: Manual of Clinical Microbiol- ogy. 4th ed. Washington, D.C.: American Society for Microbiology, 1985;129-37. Garner JS, Favero MS. Guideline for handwashing and hospital environmental control, 1985. Atlan- ta Georgia: Centers for Disease Control, 1985. Publication no. 99-1117. Kneedler JA, Dodge GH. Perioperative patient care. Boston: Blackwell Scientific Publications, 1983: 210-1. Martin LS, McDougal JS, Loskoski SL. Disinfection and inactivation of the human T-lymphotropic virus type lll/lymphadenopathy-associated virus. J Infect Dis 1985;152:400-3. Food Service Sanitation Manual 1976. DHEW publication no. (FDA) 78-2081. First printing June 1978. P-13 1986 March 14; 35:152-55 Additional Recommendations to Reduce Sexual and Drug Abuse-Related Transmission of Human T-Lymphotropic Virus Type lII/ Lymphadenopathy-Associated Virus BACKGROUND Human T-lymphotropic virus type lll/lymphadenopathy-associated virus (HTLV-III/LAV), the virus that causes acquired immunodeficiency syndrome (AIDS), is transmitted through sexual contact, parenteral exposure to infected blood or blood components, and perinatally from mother to fetus or neonate. In the United States, over 73% of adult AIDS patients are homosexual or bisexual men; 11% of these males also had a history of intravenous (IV) drug abuse. Seventeen percent of all adult AIDS patients were heterosexual men or women who abused IV drugs (7,2). The prevalence of HTLV-III/LAV antibody is high in certain risk groups in the United States (3,4). Since a large proportion of seropositive asymptomatic persons have been shown to be viremic (5), all seropositive individuals, whether symptomatic or not, must be presumed capa- ble of transmitting this infection. A repeatedly reactive serologic test for HTLV-IlII/LAV has im- portant medical, as well as public health, implications for the individual and his/her health-care provider. The purpose of these recommendations is to suggest ways to facilitate identification of seropositive asymptomatic persons, both for medical evaluation and for counseling to pre- vent transmission. Previous U.S. Public Health Service recommendations pertaining to sexual, IV drug abuse, and perinatal transmission of HTLV-III/LAV have been published (6-8). Reduction of sexual and IV transmission of HTLV-III/LAV should be enhanced by using available serologic tests to give asymptomatic, infected individuals in high-risk groups the opportunity to know their status so they can take appropriate steps to prevent the further transmission of this virus. Since the objective of these additional recommendations is to help interrupt transmission by encouraging testing and counseling among persons in high-risk groups, careful attention must be paid to maintaining confidentiality and to protecting records from any unauthorized disclosure. The ability of health departments to assure confidentiality —and the public confi- dence in that ability — are crucial to efforts to increase the number of persons requesting such testing and counseling. Without appropriate confidentiality protection, anonymous testing should be considered. Persons tested anonymously would still be offered medical evaluation and counseling. PERSONS AT INCREASED RISK OF HTLV-III/LAV INFECTION Persons at increased risk of HTLV-III/LAV infection include: (1) homosexual and bisexual men; (2) present or past IV drug abusers; (3) persons with clinical or laboratory evidence of in- fection, such as those with signs or symptoms compatible with AIDS or AIDS-related com- plex (ARC); (4) persons born in countries where heterosexual transmission is thought to play a major role*; (5) male or female prostitutes and their sex partners; (6) sex partners of infected persons or persons at increased risk; (7) all persons with hemophilia who have received clotting-factor products; and (8) newborn infants of high-risk or infected mothers. RECOMMENDATIONS 1. Community health education programs should be aimed at members of high-risk groups to: (a) increase knowledge of AIDS; (b) facilitate behavioral changes to reduce risks of HTLV-III/LAV infection; and (c) encourage voluntary testing and counseling. 2. Counseling and voluntary serologic testing for HTLV-III/LAV should be routinely offered to all persons at increased risk when they present to health-care settings. Such facilities in- clude, but are not limited to, sexually transmitted disease clinics, clinics for treating paren-. teral drug abusers, and clinics for examining prostitutes. a. Persons with a repeatedly reactive test result (see section on Test Interpretation) should receive a thorough medical evaluation, which may include history, physical examination, and appropriate laboratory studies. b. High-risk persons with a negative test result should be counseled to reduce their risk of becoming infected by: (1) Reducing the number of sex partners. A stable, mutually monogamous relationship with an uninfected person eliminates any new risk of sexually transmitted HTLV-lIl/ LAV infection. (2) Protecting themselves during sexual activity with any possibly infected person by taking appropriate precautions to prevent contact with the person's blood, semen, *e.g., Haiti, Central African countries. pP-14 urine, feces, saliva, cervical secretions, or vaginal secretions. Although the efficacy of condoms in preventing infections with HTLV-III/LAV is still under study, consis- tent use of condoms should reduce transmission of HTLV-III/LAV by preventing exposure to semen and infected lymphocytes (9,70). (3) For IV drug abusers, enrolling or continuing in programs to eliminate abuse of IV substances. Needles, other apparatus, and drugs must never be shared. c. Infected persons should be counseled to prevent the further transmission of HTLV-III/ LAV by: (1) Informing prospective sex partners of his/her infection with HTLV-III/LAV, so they can take appropriate precautions. Clearly, abstention from sexual activity with another person is one option that would eliminate any risk of sexually transmitted HTLV-III/LAV infection. (2) Protecting a partner during any sexual activity by taking appropriate precautions to prevent that individual from coming into contact with the infected person’s biood, semen, urine, feces, saliva, cervical secretions, or vaginal secretions. Although the efficacy of using condoms to prevent infections with HTLV-III/LAV is still under study, consistent use of condoms should reduce transmission of HTLV-III/LAV by preventing exposure to semen and infected lymphocytes (9,70). (3) Informing previous sex partners and any persons with whom needles were shared of their potential exposure to HTLV-III/LAV and encouraging them to seek counseling/ testing. (4) For IV drug abusers, enrolling or continuing in programs to eliminate abuse of IV substances. Needles, other apparatus, and drugs must never be shared. (5) Not sharing toothbrushes, razors, or other items that could become contaminated with blood. (6) Refraining from donating blood, plasma, body organs, other tissue, or semen. (7) Avoiding pregnancy until more is known about the risks of transmitting HTLV-IIl/ LAV from mother to fetus or newborn (8). (8) Cleaning and disinfecting surfaces on which blood or other body fluids have spilled, in accordance with previous recommendations (2). (9) Informing physicians, dentists, and other appropriate health professionals of his/her antibody status when seeking medical care so that the patient can be ap- propriately evaluated. 3. Infected patients should be encouraged to refer sex partners or persons with whom they have shared needles to their health-care provider for evaluation and/or testing. If patients prefer, trained health department professionals should be made available to assist in notifying their partners and counseling them regarding evaluation and/or testing. 4. Persons with a negative test result should be counseled regarding their need for continued evaluation to monitor their infection status if they continue high-risk behavior (8). 5. State and local health officials should evaluate the implications of requiring the reporting of repeatedly reactive HTLV-III/LAV antibody test results to the state health department. 6. State or local action is appropriate on public health grounds to regulate or close establish- ments where there is evidence that they facilitate high-risk behaviors, such as anonymous sexual contacts and/or intercourse with multiple partners or IV drug abuse (e.g., bath- houses, houses of prostitution, “shooting galleries”). TEST INTERPRETATION Commercially available tests to detect antibody to HTLV-III/LAV are enzyme-linked immu- nosorbant assays (ELISAs) using antigens derived from disrupted HTLV-III/LAV. When the ELISA is reactive on initial testing, it is standard procedure to repeat the test on the same specimen. Repeatedly reactive tests are highly sensitive and specific for HTLV-III/LAV anti- body. However, since falsely positive tests occur, and the implications of a positive test are serious, additional more specific tests (e.g., Western blot, immunofluorescent assay, etc.) are recommended following repeatedly reactive ELISA results, especially in low-prevalence popu- lations. If additional more specific test results are not readily available, persons in high-risk groups with strong repeatedly reactive ELISA results can be counseled before any additional test results are received regarding their probable infection status, their need for medical follow-up, and ways to reduce further transmission of HTLV-III/LAV. OTHER CONSIDERATIONS State or local policies governing informing and counseling sex partners and those who share needles with persons who are HTLV-IlI/LAV-antibody positive will vary, depending on state and local statutes that authorize such actions. Accomplishing the objective of interrupt- ing transmission by encouraging testing and counseling among persons in high-risk groups P-15 will depend heavily on health officials paying careful attention to maintaining confidentiality and protecting records from unauthorized disclosure. The public health effectiveness of various approaches to counseling, sex-partner referral, and laboratory testing will require careful monitoring. The feasibility and efficacy of each of these measures should be evaluated by state and local health departments to best utilize available resources. Developed by Center for Prevention Svcs and Center for Infectious Diseases, CDC, in consultation with persons from numerous other organizations and groups. References 7 2. 10. Curran JW, Morgan WM, Hardy AM, Jaffe HW, Darrow WW, Dowdle WR. The epidemiology of AIDS: current status and future prospects. Science 1985;229:1352-7. CDC. Recommendations for preventing transmission of infection with human T-lymphotropic virus type lll/lymphadenopathy-associated virus in the workplace. MMWR 1985;34:682-6, 691-5. CDC. Update: acquired immunodeficiency syndrome in the San Francisco cohort study, 1978-1985. MMWR 1985,34:573-5. CDC. Heterosexual transmission of human T-lymphotropic virus type Ill/lymphadenopathy- associated virus. MMWR 1985;34:561-3. CDC. Provisional public health services inter-agency recommendations for screening donated blood and plasma for antibody to the virus causing acquired immunodeficiency syndrome. MMWR 1985;34:1-5. CDC. Prevention of acquired immune deficiency syndrome (AIDS): report of inter-agency recom- mendations. MMWR 1983;32:101-4. CDC. Antibodies to a retrovirus etiologically associated with acquired immunodeficiency syndrome (AIDS) in populations with increased incidences of the syndrome. MMWR 1984,33:377-9. CDC. Recommendations for assisting in the prevention of perinatal transmission of human T- lymphotropic virus type lll/lymphadenopathy-associated virus and acquired immunodeficiency syn- drome. MMWR 1985,34:721-32. Judson FN, Bodin GF, Levin MJ, Ehret JM, Masters HB. In vitro tests demonstrate condoms provide an effective barrier against chlamydia trachomatis and herpes simplex virus. Abstract in Program of the International Society for STD Research, Seattle, Washington, August 1-3, 1983:176. Conant MA, Spicer DW, Smith CD. Herpes simplex virus transmission: condom studies. Sex Transm Dis 1984;11:94-5. Il. HEALTH-CARE WORKERS AND LABORATORY PERSONNEL 1982 Nov 5;31:577-80 Acquired Immune Deficiency Syndrome (AIDS): Precautions for Clinical and Laboratory Staffs The etiology of the underlying immune deficiencies seen in AIDS cases is unknown. One hypothesis consistent with current observations is that a transmissible agent may be involved. If so, transmission of the agent would appear most commonly to require intimate, direct con- tact involving mucosal surfaces, such as sexual contact among homosexual males, or through parenteral spread, such as occurs among intravenous drug abusers and possibly hemophilia patients using Factor VIII products. Airborne spread and interpersonal spread through casual contact do not seem likely. These patterns resemble the distribution of disease and modes of spread of hepatitis B virus, and hepatitis B virus infections occur very frequently among AIDS cases. There is presently no evidence of AIDS transmission to hospital personnel from contact with affected patients or clinical specimens. Because of concern about a possible transmissi- ble agent, however, interim suggestions are appropriate to guide patient-care and laboratory personnel, including those whose work involves experimental animals. At present, it appears prudent for hospital personnel to use the same precautions when caring for patients with AIDS as those used for patients with hepatitis B virus infection, in which blood and body fluids likely to have been contaminated with blood are considered infective. Specifically, patient-care and laboratory personnel should take precautions to avoid direct contact of skin and mucous membranes with blood, blood products, excretions, secretions, and tissues of persons judged likely to have AIDS. The following precautions do not specifically address out- patient care, dental care, surgery, necropsy, or hemodialysis of AIDS patients. In general, procedures appropriate for patients known to be infected with hepatitis B virus are advised, and blood and organs of AIDS patients should not be donated. The precautions that follow are advised for persons and specimens from persons with: op- portunistic infections that are not associated with underlying immunosuppressive disease or therapy; Kaposi's sarcoma (patients under 60 years of age); chronic generalized lymphade- nopathy, unexplained weight loss and/or prolonged unexplained fever in persons who belong to groups with apparently increased risks of AIDS (homosexual males, intravenous drug abus- ers, Haitian entrants, hemophiliacs); and possible AIDS (hospitalized for evaluation). Hospitals and laboratories should adapt the following suggested precautions to their individual circum- stances; these recommendations are not meant to restrict hospitals from implementing addi- tional precautions. A. The following precautions are advised in providing care to AIDS patients: 1. Extraordinary care must be taken to avoid accidental wounds from sharp instruments contaminated with potentially infectious material and to avoid contact of open skin le- sions with material from AIDS patients. 2. Gloves should be worn when handling blood specimens, blood-soiled items, body fluids, excretions, and secretions, as well as surfaces, materials, and objects exposed to them. 3. Gowns should be worn when clothing may be soiled with body fluids, blood, secretions, or excretions. 4. Hands should be washed after removing gowns and gloves and before leaving the rooms of known or suspected AIDS patients. Hands should also be washed thoroughly and im- mediately if they become contaminated with blood. 5. Blood and other specimens should be labeled prominently with a special warning, such as “Blood Precautions” or “AIDS Precautions.” If the outside of the specimen container is visibly contaminated with blood, it should be cleaned with a disinfectant (such as a 1:10 dilution of 5.25% sodium hypochlorite [household bleach] with water). All blood speci- mens should be placed in a second container, such as an impervious bag, for transport. The container or bag should be examined carefully for leaks or cracks. 6. Blood spills should be cleaned up promptly with a disinfectant solution, such as sodium hypochlorite (see above). 7. Articles soiled with blood should be placed in an impervious bag prominently labeled “AIDS Precautions” or “Blood Precautions” before being sent for reprocessing or dispos- al. Alternatively, such contaminated items may be placed in plastic bags of a particular P-18 10. color designated solely for disposal of infectious wastes by the hospital. Disposable items should be incinerated or disposed of in accord with the hospital's policies for dis- posal of infectious wastes. Reusable items should be reprocessed in accord with hospital policies for hepatitis B virus-contaminated items. Lensed instruments should be sterilized after use on AIDS patients. Needles should not be bent after use, but should be promptly placed in a puncture- resistant container used solely for such disposal. Needles should not be reinserted into their original sheaths before being discarded into the container, since this is a common cause of needle injury. Disposable syringes and needles are preferred. Only needle-locking syringes or one-piece needle-syringe units should be used to aspirate fluids from patients, so that collected fluid can be safely discharged through the needle, if desired. If reusable syringes are em- ployed, they should be decontaminated before reprocessing. A private room is indicated for patients who are too ill to use good hygiene, such as those with profuse diarrhea, fecal incontinence, or altered behavior secondary to central nervous system infections. Precautions appropriate for particular infections that concurrently occur in AIDS patients should be added to the above, if needed. B. The following precautions are advised for persons performing laboratory tests or studies on clinical specimens or other potentially infectious materials (such as inoculated tissue cul- tures, embryonated eggs, animal tissues, etc.) from known or suspected AIDS cases: 2. 3 9. C. Mechanical pipetting devices should be used for the manipulation of all liquids in the laboratory. Mouth pipetting should not be allowed. Needles and syringes should be handled as stipulated in Section A (above). Laboratory coats, gowns, or uniforms should be worn while working with potentially in- fectious materials and should be discarded appropriately before leaving the laboratory. Gloves should be worn to avoid skin contact with blood, specimens containing blood, blood-soiled items, body fluids, excretions, and secretions, as well as surfaces, materials, and objects exposed to them. All procedures and manipulations of potentially infectious material should be performed carefully to minimize the creation of droplets and aerosols. Biological safety cabinets (Class | or Il) and other primary containment devices (e.g., cen- trifuge safety cups) are advised whenever procedures are conducted that have a high potential for creating aerosols or infectious droplets. These include centrifuging, blending, sonicating, vigorous mixing, and harvesting infected tissues from animals or embryonat- ed eggs. Fluorescent activated cell sorters generate droplets that could potentially result in infectious aerosols. Translucent plastic shielding between the droplet-collecting area and the equipment operator should be used to reduce the presently uncertain magnitude of this risk. Primary containment devices are also used in handling materials that might contain concentrated infectious agents or organisms in greater quantities than expected in clinical specimens. . Laboratory work surfaces should be decontaminated with a disinfectant, such as sodium hypochlorite solution (see A5 above), following any spill of potentially infectious material and at the completion of work activities. ’ All potentially contaminated materials used in laboratory tests should be decontaminated, preferably by autoclaving, before disposal or reprocessing. All personnel should wash their hands following completion of laboratory activities, removal of protective clothing, and before leaving the laboratory. The following additional precautions are advised for studies involving experimental ani- mals inoculated with tissues or other potentially infectious materials from individuals with known or suspected AIDS. i: Laboratory coats, gowns, or uniforms should be worn by personnel entering rooms hous- ing inoculated animals. Certain nonhuman primates, such as chimpanzees, are prone to throw excreta and to spit at attendants; personnel attending inoculated animals should wear molded surgical masks and goggles or other equipment sufficient to prevent poten- tially infective droplets from reaching the mucosal surfaces of their mouths, nares, and eyes. In addition, when handled, other animals may disturb excreta in their bedding. Therefore, the above precautions should be taken when handling them. . Personnel should wear gloves for all activities involving direct contact with experimental animals and their bedding and cages. Such manipulations should be performed carefully to minimize the creation of aerosols and droplets. P-19 3. Necropsy of experimental animals should be conducted by personnel wearing gowns and gloves. If procedures generating aerosols are performed, masks and goggles should be worn. 4. Extraordinary care must be taken to avoid accidental sticks or cuts with sharp instru- ments contaminated with body fluids or tissues of experimental animals inoculated with material from AIDS patients. 5. Animal cages should be decontaminated, preferably by autoclaving, before they are cleaned and washed. 6. Only needle-locking syringes or one-piece needle-syringe units should be used to inject potentially infectious fluids into experimental animals. The above precautions are intended to apply to both clinical and research laboratories. Bi- ological safety cabinets and other safety equipment may not be generally available in clinical laboratories. Assistance should be sought from a microbiology laboratory, as needed, to assure containment facilities are adequate to permit laboratory tests to be conducted safely. Reported by Hospital Infections Program, Div of Viral Diseases, Div of Host Factors, Div of Hepatitis and Viral Enteritis, AIDS Activity, Center for Infectious Diseases, Office of Biosafety, CDC, Div of Safety, Na- tional Institutes of Health. 1983 Sept 2,32:450-51 Acquired Immunodeficiency Syndrome (AIDS): Precautions for Health-Care Workers and Allied Professionals Acquired immunodeficiency syndrome (AIDS) was first recognized in 1981. The epide- miology of AIDS is consistent with the hypothesis that it is caused by a transmissible infec- tious agent (7-3). AIDS appears to be transmitted by intimate sexual contact or by percutane- ous inoculation of blood or blood products. There has been no evidence of transmission by casual contact or airborne spread, nor have there been cases of AIDS in health-care or labora- tory personnel that can be definitely ascribed to specific occupational exposures (4). CDC has published recommended precautions for clinical and laboratory personnel who work with AIDS patients (5). Precautions for these and allied professionals are designed to minimize the risk of mucosal or parenteral exposure to potentially infective materials. Such exposure can occur during direct patient care or while working with clinical or laboratory specimens and from inadvertent or unknowing exposure to equipment, such as needles, con- taminated with potentially infective materials. Caution should be exercised in handling secre- tions or excretions, particularly blood and body fluids, from the following: (1) patients who meet the existing surveillance definition of AIDS (7); (2) patients with chronic, generalized lymphadenopathy, unexplained weight loss, and/or prolonged unexplained fever when the pa- tient’s history suggests an epidemiologic risk for AIDS (7,2); and (3) all hospitalized patients with possible AIDS. These principles for preventing AIDS transmission also need to be adopted by allied pro- fessionals not specifically addressed in the previous publications but whose work may bring them into contact with potentially infective material from patients with the illnesses described in the above three groups. The following precautions are recommended for those who provide dental care, perform postmortem examinations, and perform work as morticians when working with persons with histories of illnesses described in the above three groups: DENTAL-CARE PERSONNEL 1. Personnel should wear gloves, masks, and protective eyewear when performing dental or oral surgical procedures. 2. Instruments used in the mouths of patients should be sterilized after use (5-9). PERSONS PERFORMING NECROPSIES OR PROVIDING MORTICIANS’ SERVICES 1. As part of immediate postmortem care, deceased persons should be identified as be- longing to one of the above three groups, and that identification should remain with the body. 2. The procedures followed before, during, and after the postmortem examination are similar to those for hepatitis B. All personnel involved in performing an autopsy should wear double gloves, masks, protective eyewear, gowns, waterproof aprons, and water- proof shoe coverings. Instruments and surfaces contaminated during the postmortem examination should be handled as potentially infective items (5-7). 3. Morticians should evaluate specific procedures used in providing mortuary care and take appropriate precautions to prevent the parenteral or mucous-membrane exposure of personnel to body fluids. P-20 These and earlier recommendations outline good infection control and laboratory practices and are similar to the recommendations for prevention of hepatitis B. As new information be- comes available on the cause and transmission of AIDS, these precautions will be revised as necessary. Reported by AIDS Activity, Div of Host Factors, Div of Viral Diseases, Hospital Infections Program, Center for Infectious Diseases, Office of Biosafety, COC References 1. CDC. Update on acquired immune deficiency syndrome (AIDS)—United States. MMWR 1982,;31:507-8, 513-4. 2. Jaffe HW, Choi K, Thomas PA, et al. National case-control study of Kaposi's sarcoma and Pneu- mocystis carinii pneumonia in homosexual men: Part 1, epidemiologic results. Ann Intern Med 1983,99:145-51. 3. Francis DP, Curran JW, Essex M. Epidemic acquired immune deficiency syndrome: Epidemiologic evi- dence for a transmissible agent. (guest editorial) JNCI 1983,71:1-4. 4. CDC. An evaluation of acquired immunodeficiency syndrome (AIDS) reported in health-care personnel— United States. MMWR 1983,32:358-60. 5. CDC. Acquired immune deficiency syndrome (AIDS): precautions for clinical and laboratory staffs. MMWR 1982,;31:577-80. 6. Simmons BP, with Hooton TM, Mallison GF. Guidelines for hospital environmental control. Infect Con- trol 1981, 2:131-46. 7. CDC guidelines on infection control. Guidelines for hospital environmental control (continued). Infect Control 1982;3:52-60. 8. Garner JS, Simmons BP. CDC guideline for isolation precautions in hospitals. Infect Control 1983.4:245-325. 9. Cooley RL, Lubow RM. AIDS: an occupational hazard? J Am Dent Assoc 1983;107:28-31. 1985 Aug 30;34:533—-34 Recommendations for Preventing Possible Transmission of Human T-Lymphotropic Virus Type IlI/ Lymphadenopathy-Associated Virus from Tears Human T-lymphotropic virus type Ill/lymphadenopathy-associated virus (HTLV-III/LAV), the etiologic agent of acquired immunodeficiency syndrome (AIDS), has been found in various body fluids, including blood, semen, and saliva. Recently, scientists at the National Institutes of Health isolated the virus from the tears of an AIDS patient (7). The patient, a 33-year-old woman with a history of Pneumocystis carinii pneumonia and disseminated Mycobacterium avium-intracellulare infection, had no ocular complaints, and her eye examination was normal. Of the tear samples obtained from six other patients with AIDS or related conditions, three showed equivocal culture results, and three were culture-negative. The following precautions are judged suitable to prevent spread of HTLV-III/LAV and other microbial pathogens that might be present in tears. They do not apply to the procedures used by individuals in caring for their own lenses, since the concern is the possible virus transmis- sion between individuals. 1. Health-care professionals performing eye examinations or other procedures involving contact with tears should wash their hands immediately after a procedure and between patients. Handwashing alone should be sufficient, but when practical and convenient, disposable gloves may be worn. The use of gloves is advisable when there are cuts, scratches, or dermatologic lesions on the hands. Use of other protective measures, such as masks, goggles, or gowns, is not indicated. 2. Instruments that come into direct contact with external surfaces of the eye should be wiped clean and then disinfected by: (a) a 5- to 10-minute exposure to a fresh solution of 3% hydrogen peroxide; or (b) a fresh solution containing 5,000 parts per million (mg/L) free available chlorine—a 1/10 dilution of common household bleach (sodium hypochlorite); or (c) 70% ethanol; or (d) 70% isopropanol. The device should be thor- oughly rinsed in tap water and dried before reuse. 3. Contact lenses used in trial fittings should be disinfected between each fitting by one of the following regimens: a. Disinfection of trial hard lenses with a commercially available hydrogen peroxide contact lens disinfecting system currently approved for soft contact lenses. (Other hydrogen peroxide preparations may contain preservatives that could discolor the lenses.) Alternatively, most trial hard lenses can be treated with the standard heat disinfection regimen used for soft lenses (78-80 C [172-176 F] for 10 minutes). Practitioners should check with hard lens suppliers to ascertain which lenses can be safely heat-treated. b. Rigid gas permeable (RGP) trial fitting lenses can be disinfected using the above hydrogen peroxide disinfection system. RGP lenses may warp if they are heat- disinfected. c. Soft trial fitting lenses can be disinfected using the same hydrogen peroxide system. Some soft lenses have also been approved for heat disinfection. Other than hydrogen peroxide, the chemical disinfectants used in standard contact lens solutions have not yet been tested for their activity against HTLV-III/LAV. Until other disinfectants are shown to be suitable for disinfecting HTLV-III/LAV, contact lenses used in the eyes of patients suspected or known to be infected with HTLV-III/LAV are most safely handled by hydrogen peroxide disinfection. The above recommendations are based on data from studies conducted at the National In- stitutes of Health and CDC on disinfection/inactivation of HTLV-III/LAV virus (2-4). Additional information regarding general hospital and laboratory precautions have been previously pub- lished (5-9). Reported by the U.S. Food and Drug Administration, National Institutes of Health, Centers for Disease Control. Editorial Note: All secretions and excretions of an infected person may contain lymphocytes, host cells for HTLV-III/LAV; therefore, thorough study of these fluids might be expected to sometimes yield this virus. Despite positive cultures from a variety of body fluids of infected persons, however, spread from infected persons to household contacts who have no other identifiable risks for infection has not been documented. Furthermore, there is no evidence to date that HTLV-III/LAV has been transmitted through contact with the tears of infected indi- viduals or through medical instruments used to examine AIDS patients. References 1. Fujikawa LS, Salahuddin SZ, Palestine AG, et al. Isolation of human T-cell leukemia/lymphotropic virus type Ill (HTLV-II) from the tears of a patient with acquired immunodeficiency syndrome (AIDS). Lancet (in press). 2. Resnick L, Veren K, Salahuddin SZ, Markham PD. Personal communication. 3. Martin LS, McDougal JS, Loskoski SL. Disinfection and inactivation of the human T lymphotropic virus type lll/lymphadenopathy-associated virus. J Infect Dis 1985;152:400-3. 4. Spire B, Barre-Sinoussi F, Montagnier L, Chermann JC. Inactivation of a new retrovirus (lymphade- nopathy-associated virus) by various agents (chemical disinfectants). Lancet 1984:8408;899-901. 5. CDC. Acquired immune deficiency syndrome (AIDS): precautions for clinical and laboratory staffs. MMWR 1982,;31:577-80. 6. CDC. Prevention of acquired immune deficiency syndrome (AIDS): report of inter-agency recommen- dations. MMWR 1983;32:101-4. 7. CDC. Acquired immunodeficiency syndrome (AIDS): precautions for health-care workers and allied professionals. MMWR 1983,32:450-1. 8. CDC. Update: prospective evaluation of health-care workers exposed via parenteral or mucous- membrane route to blood or body fluids from patients with acquired immunodeficiency syndrome. MMWR 1985;34:101-3. 9. CDC. Hepatitis B vaccine: evidence confirming lack of AIDS transmission. MMWR 1984,33:685-7. 1986 April 11, 35:221-23 Recommendations for Preventing Transmission of Infection with Human T-Lymphotropic Virus Type Ill/ Lymphadenopathy-Associated Virus during Invasive Procedures BACKGROUND On November 15, 1985, “Recommendations for Preventing Transmission of Infection with Human T-Lymphotropic Virus Type lll/Lymphadenopathy-Associated Virus in the Work- place,” was published (7). That document gave particular emphasis to health-care settings and indicated that formulation of further specific recommendations for preventing human T- lymphotropic virus type lll/lymphadenopathy-associated virus (HTLV-III/LAV) transmission applicable to health-care workers (HCWs) who perform invasive procedures was in progress. Toward that end, a 2-day meeting was held at CDC to discuss draft recommendations ap- plicable to individuals who perform or assist in invasive procedures.* Following the meeting, revised draft recommendations for HCWs who have contact with tissues or mucous mem- branes while performing or assisting in operative, obstetric, or dental invasive procedures were sent to participants for comment. In addition, 10 physicians with expertise in infectious diseases and the epidemiology of HTLV-III/LAV infection were consulted to determine wheth- er they felt additional measures or precautions beyond those recommended below were in- dicated. These 10 experts did not feel that additional recommendations or precautions were indicated. DEFINITIONS In this document, an operative procedure is defined as surgical entry into tissues, cavities, or organs or repair of major traumatic injuries in an operating or delivery room, emergency department, or outpatient setting, including both physicians’ and dentists’ offices. An obstet- ric procedure is defined as a vaginal or cesarean delivery or other invasive obstetric procedure where bleeding may occur. A dental procedure is defined as the manipulation, cutting, or removal of any oral or perioral tissues, including tooth structure, where bleeding occurs or the potential for bleeding exists. RECOMMENDATIONS There have been no repcrts of HTLV-III/LAV transmission from an HCW to a patient or from a patient to an HCW during operative, obstetric, or dental invasive procedures. Neverthe- less, special emphasis should be placed on the following precautions to prevent transmission of bloodborne agents between all patients and all HCWs who perform or assist in invasive procedures. 1. All HCWs who perform or assist in operative, obstetric, or dental invasive procedures must be educated regarding the epidemiology, modes of transmission, and prevention of HTLV-III/LAV infection and the need for routine use of appropriate barrier precautions during procedures and when handling instruments contaminated with blood after procedures. 2. All HCWs who perform or assist in invasive procedures must wear gloves when touch- ing mucous membranes or nonintact skin of all patients and use other appropriate bar- rier precautions when indicated (e.g., masks, eye coverings, and gowns, if aerosolization or splashes are likely to occur). In the dental setting, as in the operative and obstetric setting, gloves must be worn for touching all mucous membranes and changed between all patient contacts. If a glove is torn or a needlestick or other injury occurs, the glove must be changed as promptly as safety permits and the needle or instrument removed from the sterile field. ‘The following organizations were represented at the meeting: American Academy of Family Physicians; American Academy of Periodontology; American Association of Dental Schools, American Association of Medical Colleges; American Association of Oral and Maxillofacial Surgeons; American Association of Physicians for Human Rights; American College of Emergency Physicians; American College of Nurse Midwives; American College of Obstetricians and Gynecologists; American College of Surgeons; Ameri- can Dental Association; American Dental Hygienists Association; American Hospital Association; Ameri- can Medical Association; American Nurses’ Association; American Public Health Association; Association for Practitioners in Infection Control; Association of Operating Room Nurses; Association of State and Territorial Health Officials; Conference of State and Territorial Epidemiologists; U.S. Food and Drug Ad- ministration; Infectious Diseases Society of America; National Association of County Health Officials; Na- tional Dental Association; National Institutes of Health; National Medical Association; Nurses Association of the American College of Obstetricians and Gynecologists; Society of Hospital Epidemiologists of America; Surgical Infection Society; and United States Conference of Local Health Officers. In addition, a hospital administrator, a hospital medical director, and representatives from CDC participated in the meet- ing. These recommendations may not reflect the views of all individual consultants or the organizations they represented. P-23 3. All HCWs who perform or assist in vaginal or cesarean deliveries must use appropriate barrier precautions (e.g., gloves and gowns) when handling the placenta or the infant until blood and amniotic fluid have been removed from the infant's skin. Recommenda- tions for assisting in the prevention of perinatal transmission of HTLV-III/LAV have been published (2) 4. All HCWs who perform or assist in invasive procedures must use extraordinary care to prevent injuries to hands caused by needles, scalpels, and other sharp instruments or devices during procedures; when cleaning used instruments; during disposal of used needles; and when handling sharp instruments following procedures. After use, dis- posable syringes and needles, scalpel blades, and other sharp items must be placed in puncture-resistant containers for disposal. To prevent needlestick injuries, needles should not be recapped; purposefully bent or broken; removed from disposable sy- ringes; or otherwise manipulated by hand. No data are currently available from con- trolled studies examining the effect, if any, of the use of needle-cutting devices cn the incidence of needlestick injuries. 5. If an incident occurs during an invasive procedure that results in exposure of a patient to the blood of an HCW, the patient should be informed of the incident, and previous recommendations for management of such exposures (7) should be followed. 6. No HCW who has exudative lesions or weeping dermatitis should perform or assist in invasive procedures or other direct patient-care activities or handle equipment used for patient care. 7. All HCWs with evidence of any illness that may compromise their ability to adequately and safely perform invasive procedures should be evaluated medically to determine whether they are physically and mentally competent to perform invasive procedures. 8. Routine serologic testing for evidence of HTLV-III/LAV infection is not necessary for HCWs who perform or assist in invasive procedures or for patients undergoing invasive procedures, since the risk of transmission in this setting is so low. Results of such rou- tine testing would not practically supplement the precautions recommended above in further reducing the negligible risk of transmission during operative, obstetric, or dental invasive procedures. Previous recommendations (7,3,4) should be consulted for: (1) preventing transmission of HTLV-III/LAV infection from HCWs to patients and patients to HCWs in health-care settings other than those described in this document; (2) preventing transmission from patient to pa- tient; (3) sterilizing, disinfecting, housekeeping, and disposing of waste; and (4) managing parenteral and mucous-membrane exposures of HCWs and patients. Previously recommended precautions (7) are also applicable to HCW performing or assisting in invasive procedures. References 1. CDC. Recommendations for preventing transmission of infection with human T-lymphotropic virus type lll/lymphadenopathy-associated virus in the workplace. MMWR 1985,34.682-6, 691-5. 2. CDC. Recommendations for assisting in the prevention of perinatal transmission of human T- lymphotropic virus type lll/lymphadenopathy-associated virus and acquired immunodeficiency syn- drome. MMWR 1985,34:721-6, 731-2. 3. CDC. Acquired immune deficiency syndrome (AIDS): precautions for clinical and laboratory staffs. MMWR 1982;31.577-80. 4. CDC. Acquired immunodeficiency syndrome (AIDS): precautions for health-care workers and allied professionals. MMWR 1983;32:450-1 1986 April 18; 35:237—42 Recommended Infection-Control Practices for Dentistry Dental personnel may be exposed to a wide variety of microorganisms in the blood and saliva of patients they treat in the dental operatory. These include Mycobacterium tuberculosis, hepatitis B virus, staphylococci, streptococci, cytomegalovirus, herpes simplex virus types | and ll, human T-lymphotropic virus type lll/lymphadenopathy-associated virus (HTLV-lI/ LAV), and a number of viruses that infect the upper respiratory tract. Infections may be trans- mitted in dental practice by blood or saliva through direct contact, droplets, or aerosols. Al- though not documented, indirect contact transmission of infection by contaminated instru- ments is possible. Patients and dental health-care workers (DHCWs) have the potential of transmitting infections to each other (7). A common set of infection-control strategies should be effective for preventing hepatitis B, acquired immunodeficiency syndrome, and other infectious diseases caused by bloodborne viruses (2-4). The ability of hepatitis B virus to survive in the environment (5) and the high P-24 titers of virus in blood (6) make this virus a good model for infection-control practices to pre- vent transmission of a large number of other infectious agents by blood or saliva. Because all in- fected patients cannot be identified by history, physical examination, or readily available laboratory tests (3), the following recommendations should be used routinely in the care of all patients in dental practices MEDICAL HISTORY Always obtain a thorough medical history. Include specific questions about medications, current illnesses, hepatitis, recurrent illnesses, unintentional weight loss, lymphadenopathy, oral soft tissue lesions, or other infections. Medical consultation may be indicated when a his- tory of active infection or systemic disease is elicited. USE OF PROTECTIVE ATTIRE AND BARRIER TECHNIQUES 1. For protection of personnel and patients, gloves must always be worn when touching blood, saliva, or mucous membranes (7-70). Gloves must be worn by DHCWs when touching blood-soiled items, body fluids, or secretions, as well as surfaces contaminated with them. Gloves must be worn when examining all oral lesions. All work must be completed on one pa- tient, where possible, and the hands must be washed and regloved before performing proce- dures on another patient. Repeated use of a single pair of gloves is not recommended, since such use is likely to produce defects in the glove material, which will diminish its value as an effective barrier. 2. Surgical masks and protective eyewear or chin-length plastic face shields must be worn when splashing or spattering of blood or other body fluids is likely, as is common in den- tistry (77,712). 3. Reusable or disposable gowns, laboratory coats, or uniforms must be worn when cloth- ing is likely to be soiled with blood or other body fluids. If reusable gowns are worn, they may be washed, using a normal laundry cycle. Gowns should be changed at least daily or when visibly soiled with blood (73). 4. Impervious-backed paper, aluminum foil, or clear plastic wrap may be used to cover surfaces (e.g., light handles or x-ray unit heads) that may be contaminated by blood or saliva and that are difficult or impossible to disinfect. The coverings should be removed (while DHCWs are gloved), discarded, and then replaced (after ungloving) with clean material be- tween patients. 5. All procedures and manipulations of potentially infective materials should be performed carefully to minimize the formation of droplets, spatters, and aerosols, where possible. Use of rubber dams, where appropriate, high-speed evacuation, and proper patient positioning should facilitate this process. HANDWASHING AND CARE OF HANDS Hands must always be washed between patient treatment contacts (following removal of gloves), after touching inanimate objects likely to be contaminated by blood or saliva from other patients, and before leaving the operatory. The rationale for handwashing after gloves have been worn is that gloves become perforated, knowingly or unknowingly, during use and allow bacteria to enter beneath the glove material and multiply rapidly. For many routine dental procedures, such as examinations and nonsurgical techniques, handwashing with plain soap appears to be adequate, since soap and water will remove transient microorganisms ac- quired directly or indirectly from patient contact (73). For surgical procedures, an antimicro- bial surgical handscrub should be used (74). Extraordinary care must be used to avoid hand injuries during procedures. However, when gloves are torn, cut, or punctured, they must be re- moved immediately, hands thoroughly washed, and regloving accomplished before comple- tion of the dental procedure. DHCWs who have exudative lesions or weeping dermatitis should refrain from all direct patient care and from handling dental patient-care equipment until the condition resolves (75). USE AND CARE OF SHARP INSTRUMENTS AND NEEDLES 1. Sharp items (needles, scalpel blades, and other sharp instruments) should be consid- ered as potentially infective and must be handled with extraordinary care to prevent uninten- tional injuries. 2. Disposable syringes and needles, scalpel blades, and other sharp items must be placed into puncture-resistant containers located as close as practical to the area in which they were used. To prevent needlestick injuries, disposable needles should not be recapped; purposefully bent or broken; removed from disposable syringes; or otherwise manipulated by hand after use. 3. Recapping of a needle increases the risk of unintentional needlestick injury. There is no evidence to suggest that reusable aspirating-type syringes used in dentistry should be handled differently from other syringes. Needles of these devices should not be recapped, bent, or broken before disposal. P-25 4. Because certain dental procedures on an individual patient may require multiple injec- tions of anesthetic or other medications from a single syringe, it would be more prudent to place the unsheathed needle into a “sterile field” between injections rather than to recap the needle between injections. A new (sterile) syringe and a fresh solution should be used for each patient INDICATIONS FOR HIGH-LEVEL DISINFECTION OR STERILIZATION OF INSTRUMENTS Surgical and other instruments that normally penetrate soft tissue and/or bone (e.g, forceps, scalpels, bone chisels, scalers, and surgical burs) should be sterilized after each use. Instruments that are not intended to penetrate oral soft tissues or bone (e.g., amalgam con- densers, plastic instruments, and burs) but that may come into contact with oral tissues should also be sterilized after each use, if possible; however, if sterilization is not feasible, the latter instruments should receive high-level disinfection (3,73,76). METHODS FOR HIGH-LEVEL DISINFECTION OR STERILIZATION Before high-level disinfection or sterilization, instruments should be cleaned to remove debris. Cleaning may be accomplished by a thorough scrubbing with soap and water or a deter- gent, or by using a mechanical device (e.g., an ultrasonic cleaner). Persons involved in cleaning and decontaminating instruments should wear heavy-duty rubber gloves to prevent hand inju- ries. Metal and heat-stable dental instruments should be routinely sterilized between use by steam under pressure (autoclaving), dry heat, or chemical vapor. The adequacy of sterilization cycles should be verified by the periodic use of spore-testing devices (e.g., weekly for most dental practices) (73). Heat- and steam-sensitive chemical indicators may be used on the out- side of each pack to assure it has been exposed to a sterilizing cycle. Heat-sensitive instruments may require up to 10 hours’ exposure in a liquid chemical agent registered by the U.S. Environ- mental Protection Agency (EPA) as a disinfectant/sterilant; this should be followed by rinsing with sterile water. High-level disinfection may be accomplished by immersion in either boiling water for at least 10 minutes or an EPA-registered disinfectant/sterilant chemical for the expo- sure time recommended by the chemical’s manufacturer. DECONTAMINATION OF ENVIRONMENTAL SURFACES At the completion of work activities, countertops and surfaces that may have become con- taminated with blood or saliva should be wiped with absorbent toweling to remove extrane- ous organic material, then disinfected with a suitable chemical germicide. A solution of sodium hypochlorite (household bleach) prepared fresh daily is an inexpensive and very effec- tive germicide. Concentrations ranging from 5,000 ppm (a 1:10 dilution of household bleach) to 500 ppm (a 1:100 dilution) sodium hypochlorite are effective, depending on the amount of organic material (e.g., blood, mucus, etc.) present on the surface to be cleaned and disinfected. Caution should be exercised, since sodium hypochlorite is corrosive to metals, especially aluminum. DECONTAMINATION OF LABORATORY SUPPLIES AND MATERIALS Blood and saliva should be thoroughly and carefully cleaned from laboratory supplies and materials that have been used in the mouth (e.g., impression materials, bite registration), espe- cially before polishing and grinding intra-oral devices. Materials, impressions, and intra-oral appliances should be cleaned and disinfected before being handled, adjusted, or sent to a dental laboratory (77). These items should also be cleaned and disinfected when returned from the dental laboratory and before placement in the patient's mouth. Because of the ever- increasing variety of dental materials used intra-orally, DHCWs are advised to consult with manufacturers as to the stability of specific materials relative to disinfection procedures. A chemical germicide that is registered with the EPA as a “hospital disinfectant” and that has a label claim for mycobactericidal (e.g., tuberculocidal) activity is preferred, because myco- bacteria represent one of the most resistant groups of microorganisms; therefore, germicides that are effective against mycobacteria are also effective against other bacterial and viral pathogens (75). Communication between a dental office and a dental laboratory with regard to handling and decontamination of supplies and materials is of the utmost importance USE AND CARE OF ULTRASONIC SCALERS, HANDPIECES, AND DENTAL UNITS 1. Routine sterilization of handpieces between patients is desirable; however, not all hand- pieces can be sterilized. The present physical configurations of most handpieces do not readi- ly lend them to high-level disinfection of both external and internal surfaces (see 2 below); therefore, when using handpieces that cannot be sterilized, the following cleaning and disin- fection procedures should be completed between each patient. After use, the handpiece should be flushed (see 2 below), then thoroughly scrubbed with a detergent and water to remove adherent material. It should then be thoroughly wiped with absorbent material saturated with a chemical germicide that is registered with the EPA as a “hospital disinfec- tant” and is mycobactericidal at use-dilution (75). The disinfecting solution should remain in P-26 contact with the handpiece for a time specified by the disinfectant’s manufacturer. Ultrasonic scalers and air/water syringes should be treated in a similar manner between patients. Follow- ing disinfection, any chemical residue should be removed by rinsing with sterile water. 2. Because water retraction valves within the dental units may aspirate infective materials back into the handpiece and water line, check valves should be installed to reduce the risk of transfer of infective material (78). While the magnitude of this risk is not known, it is prudent for water-cooled handpieces to be run and to discharge water into a sink or container for 20-30 seconds after completing care on each patient. This is intended to physically flush out patient material that may have been aspirated into the handpiece or water line. Additionally, there is some evidence that overnight bacterial accumulation can be significantly reduced by allowing water-cooled handpieces to run and to discharge water into a sink or container for several minutes at the beginning of the clinic day (79). Sterile saline or sterile water should be used as a coolant/irrigator when performing surgical procedures involving the cutting of soft tissue or bone. HANDLING OF BIOPSY SPECIMENS In general, each specimen should be put in a sturdy container with a secure lid to prevent leaking during transport. Care should be taken when collecting specimens to avoid contamina- tion of the outside of the container. If the outside of the container is visibly contaminated, it should be cleaned and disinfected, or placed in an impervious bag (20). DISPOSAL OF WASTE MATERIALS All sharp items (especially needles), tissues, or blood should be considered potentially in- fective and should be handled and disposed of with special precautions. Disposable needles, scalpels, or other sharp items should be placed intact into puncture-resistant containers before disposal. Blood, suctioned fluids, or other liquid waste may be carefully poured into a drain connected to a sanitary sewer system. Other solid waste contaminated with blood or other body fluids should be placed in sealed, sturdy impervious bags to prevent leakage of the contained items. Such contained solid wastes can then be disposed of according to require- ments established by local or state environmental regulatory agencies and published recom- mendations (73,20). Developed by Dental Disease Prevention Activity, Center for Prevention Svcs, Hospital Infections Pro- gram, Center for Infectious Diseases, COC. Editorial Note: All DHCWs must be made aware of sources and methods of transmission of infectious diseases. The above recommendations for infection control in dental practices in- corporate procedures that should be effective in preventing the transmission of infectious agents from dental patients to DHCWSs and vice versa. Assessment of quantifiable risks to dental personnel and patients for specific diseases requires further research. There is no cur- rent documentation of patient-to-patient blood- or saliva-borne disease transmission from procedures performed in dental practice. While few in number, reported outbreaks of dentist- to-patient transmission of hepatitis B have resulted in serious and even fatal consequences (9). Herpes simplex virus has been transmitted to over 20 patients from the fingers of aDHCW (70). Serologic markers for hepatitis B in dentists have increased dramatically in the United States over the past several years, which suggests current infection-control practices have been in- sufficient to prevent the transmission of this infectious agent in the dental operatory. While vaccination for hepatitis B is strongly recommended for dental personnel (27), vaccination alone is not cause for relaxation of strict adherence to accepted methods of asepsis, disinfec- tion, and sterilization. Various infection-control guidelines exist for hospitals and other clinical settings. Dental facilities located in hospitals and other institutional settings have generally utilized existing guidelines for institutional practice. These recommendations are offered as guidance to DHCWs in noninstitutional settings for enhancing infection-control practices in dentistry; they may be useful in institutional settings also. References 1. Ahtone J, Goodman RA. Hepatitis B and dental personnel. transmission to patients and prevention issues. J Am Dent Assoc 1983;106:219-22 2. Crawford JJ. State-of-the-art: practical! infection control in dentistry. J Am Dent Assoc 1985;110 629-33 3. Cottone JA, Mitchell EW, Baker CH, et al. Proceedings of the National Symposium on Hepatitis B and the Dental Profession. J Am Dent Assoc 1985;110 614-49. 4. CDC Acquired immunodeficiency syndrome (AIDS) precautions for health-care workers and allied professionals. MMWR 1983,32:450-1. 5. Bond WW, Favero MS, Petersen NJ, Gravelle CR, Ebert JW, Maynard JE Survival of hepatitis B virus after drying and storage for one week [Letter]. Lancet 1981;1:550-1 6. Shikata T, Karasawa T, Abe K, et al. Hepatitis B e antigen and infectivity of hepatitis B virus. J Infect Dis 1977,136 571-6 7 Hadler SC, Sorley DL, Acree KH, et al. An outbreak of hepatitis B in a dental practice Ann Intern Med 1981,95 133-8 8. Occupational Safety and Health Administration. Risk of hepatitis B infection for workers in the health care delivery system and suggested methods for risk reduction. U.S. Department of Labor 1983; (CPL 2-2.36) 9 CDC. Hepatitis B among dental patients — Indiana. MMWR 1985,34:73-5 10. Manzella JP, McConville JH, Valenti W, Menegus MA, Swierkosz EM, Arens M. An outbreak of herpes simplex virus type 1 gingivostomatitis in a dental hygiene practice. JAMA 1984,252 2019-22. 11 Petersen NJ, Bond WW, Favero MS. Air sampling for hepatitis B surface antigen in a dental opera- tory. J Am Dent Assoc 1979,99:465-7. 12. Bond WW, Petersen NJ, Favero MS, Ebert JW, Maynard JE. Transmission of type B viral hepatitis B via eye inoculation of a chimpanzee. J Clin Microbiol 1982,15:533-4 13. Garner JS, Favero MS. Guideline for handwashing and hospital environmental control, 1985. Atlan- ta, Georgia. Centers for Disease Control, 1985; publication no. 99-1117 14. Garner JS. Guideline for prevention of surgical wound infections, 1985. Atlanta, Georgia: Centers for Disease Control, 1985; publication no. 99-2381 15. CDC. Recommendations for preventing transmission of infection with human T-lymphotropic virus type lll/lymphadenopathy-associated virus in the workplace. MMWR 1985,34.682-6, 691-5. 16. Favero MS. Sterilization, disinfection, and antisepsis in the hospital. In: Lennette EH, Balows A, Hauslen WJ, Shadomy HJ. Manual of clinical microbiology. Washington, D.C.: American Society of Microbiology, 1985:129-37. 17. Council on Dental Therapeutics and Council on Prosthetic Services and Dental Laboratory Relations, American Dental Association. Guidelines for infection control in the dental office and the commer- cial laboratory. J Am Dent Assoc 1985;110:969-72. 18. Bagga BSR, Murphy RA, Anderson AW, Punwani |. Contamination of dental unit cooling water with oral microorganisms and its prevention. J Am Dent Assoc 1984;109:712-6. 19. Scheid RC, Kim CK, Bright JS, Whitely MS, Rosen S. Reduction of microbes in handpieces by flush- ing before use. J Am Dent Assoc 1982;105:658-60. 20. Garner JS, Simmons BP. CDC guideline for isolation precautions in hospitals. Atlanta, Georgia: Cen- ters for Disease Control, 1983; HHS publication no. (CDC) 83-8314. 21. ACIP. Inactivated hepatitis B virus vaccine. MMWR 1982;31:317-22, 327-8 1986 Aug 29;35:540—49 Human T-Lymphotropic Virus Type Ill/ Lymphadenopathy-Associated Virus: Agent Summary Statement INTRODUCTION In March 1984, CDC and the National Institutes of Health (NIH), in consultation with scien- tists, physicians, and public health workers in academia, industry, and government, published a manual entitled Biosafety in Microbiological and Biomedical Laboratories (“biosafety manual”)* (7). The manual describes combinations of standard and special microbiologic practices, safety equipment, and facilities recommended for working with infectious agents in various laboratory settings. The recommendations are advisory and provide a voluntary code of safety practices. A section of this manual is devoted to a number of specific “agent summary statements” consisting of brief descriptions of documented or anecdotal laboratory-associated infections, the nature of the laboratory hazards, and recommended precautions to be taken in handling and working with certain infectious agents. Contributors to the manual recognized that new agents would be discovered from time to time and recommended that a summary statement for each new agent be developed and published in the MMWR The summary statement for human T-lymphotropic virus type lil/lymphodenopathy-associated virus (HTLV-/LAV) T fol- lows. All laboratory directors are requested to put a copy of this summary in each of their copies of the biosafety manual and bring it to the attention of laboratory personnel. The recommendations in the summary statement were compiled from published scientific reports and are consistent with the published guidelines for health-care workers (2-4). AGENT SUMMARY STATEMENT: HTLV-III/LAV As of August 15, 1986, no cases of acquired immunodeficiency syndrome (AIDS) that meet the CDC case definition and can be attributed to an inadvertent laboratory exposure have been reported in laboratory workers (5). One laboratory worker (7) was included ‘Available from Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402, Stock #01702300167-1, Price: $4.00; and from National Technical Information Service, U.S Department of Commerce, 5285 Port Royal Road, Springfield, Virginia 22161, Stock #PB84-206879, Price: $6.00. The Human Retrovirus Subcommittee of the International Committee on the Taxonomy of Viruses has proposed the name human immunodeficiency virus (HIV) for these viruses (Science 1986,232:697) p-28 among the health-care workers who have had HTLV-III/LAV antibody detected in their serum after sustaining a needlestick injury (2,3,6-70), but the source of the infection could not be established. Persons who are infected with HTLV-III/LAV may be asymptomatic, may have AIDS-related complex, or may manifest symptoms of overt AIDS (77) In 1985, two different reagent production laboratories reported that several laboratory workers may have been inadvertently exposed to an aerosol of concentrated HTLV-III/LAV; one worker was cut by a piece of glass from a broken carboy that contained HTLV-III/ LAV-infected cells and culture fluid. None of the potentially exposed persons had shown evi- dence of seroconversion after 6 months in one incident and 12 months in the other as a result of these occupational exposures. Other reports dealing with HTLV-III/LAV infection in health-care personnel, including laboratory workers (3,4,6,8-10), indicate that the risk of bloodborne transmission from inad- vertent exposure is considerably less for HTLV-II/LAV than for hepatitis B virus infection. These reports illustrate the need for complete evaluation by a physician and serologic testing of each laboratory worker definitely or possibly exposed to HTLV-III/LAV in a laboratory set- ting. It is recommended that the Public Health Service guidelines for health-care workers be followed in these instances (2,3). Laboratory Hazards HTLV-III/LAV has been isolated from blood, semen, saliva, tears, urine, cerebrospinal fluid, brain tissue, and cervical secretions and is likely to be present in other body fluids, secretions, and tissues of infected humans or experimentally infected nonhuman primates. Percutaneous or parenteral inoculation and direct contact of cuts, scratches, abrasions, or mucosal surfaces with suspensions of virus or specimens containing live virus are considered potential routes of infection. Possible transmission of infection via the parenteral route can occur through self- inoculation with needles, broken glass, or other sharp objects that contain HTLV-III/LAV. Spill- age is a possible means of exposure and infection, especially spills accompanied by spraying or splashing of infected cell cultures, viral concentrates, and other infectious materials that may come into direct contact with abraded skin or mucous membranes of the eyes, nose, or mouth; however, there are no data documenting or suggesting that transmission of HTLV-III/ LAV has occurred in this manner. Ingestion and inhalation have not been documented as modes of transmission of the virus. Recommended Precautions 1. Biosafety Level (BSL) 2 standards and special practices, containment equipment, and facili- ties as described in the CDC-NIH biosafety manual are recommended for activities involv- ing clinical specimens, body fluids, or tissues from humans or laboratory animals that may contain HTLV-II/LAV. These are the same practices recommended for all clinical speci- mens. Emphasis is placed on the following practices, which are included in the manual (7): a. Use of syringes, needles and other sharp instruments should be avoided if possible. Used needles and cutting instruments should be discarded into a puncture-resistant container with a lid. Needles should not be resheathed, purposefully bent, broken, re- moved from disposable syringes, or otherwise manipulated by hand. b. Gloves should be worn by all personnel engaged in activities that may involve skin con- tact with potentially infectious fluids, tissues, or cultures and by laboratory workers with dermatitis or other lesions on the hands who may have direct or indirect contact with potentially infectious materials. Handwashing with soap and water should be a rou- tine practice immediately after direct contact with potentially infectious materials and on completion of work, even when gloves are worn. c. Generation of aerosols, splashes, and spills of potentially infectious materials should be avoided in procedures involving body fluids or tissues, during necropsy of cadavers, and in similar procedures on animals experimentally infected with HTLV-III/LAV. Laboratory workers should use a biological safety cabinet when propagating the virus to further reduce the risk of exposure. Although the major precautions are listed here, the CDC-NIH biosafety manual contains additional related precautions (see pages 11-13 for BSL 2 and pages 14-17 [7] for BSL 3 when large volumes or concentrates of HTLV-III/LAV are involved). In all instances, the laboratory director is responsible for assessing the biosafe- ty level to be used. d. Human serum from any source that is used as a control or reagent in a test procedure should be handled at BSL 2 (see pages 11-13 (7]). Appended to this Agent Summary Statement is a statement (Addendum 1) issued by CDC on the use of all human control or reagent sera shipped to other laboratories. The Food and Drug Administration re- quires that manufacturers of human serum reagents use a similarly worded statement. P-29 e. Animal BSL 2 practices, containment equipment, and facilities are recommended for ac- tivities involving nonhuman primates experimentally infected with HTLV-II/LAV. Laboratory coats, gowns, or uniforms should be worn by laboratory workers, as is cus- tomary for other BSL 2 or 3 practices, depending on the nature of the work, concentra- tion of the virus, and volume of material being handled. Because many animals bite, and some throw feces, urine, or expectorate at humans, animal-care personnel must wear coats, protective gloves, coveralls or uniforms, and face shields as appropriate to pro- tect the skin and mucous membranes of the eyes, nose, and mouth from potential expo- sure to these substances when working with animals likely to manifest such behavior. . Activities such as growing research-laboratory-scale amounts of HTLV-III/LAV or related viruses or virus-producing cell lines, working with concentrated virus preparations, or con- ducting procedures that may produce droplets or aerosols should be performed in a BSL 2 facility with the additional practices and containment equipment recommended for BSL 3 {12}. . Activities involving industrial-scale, large-volume, or high-concentration production and manipulation of HTLV-III/LAV are to be conducted with BSL 3 requirements (72). . All laboratory glassware, equipment, disposable materials, and wastes suspected or known to contain HTLV-III/LAV must be decontaminated, preferably in an autoclave, before wash- ing, discarding, etc. Incineration of solid wastes may be used as an alternate method of disposal. . There is no evidence that laboratory clothing soiled with materials known or suspected to contain HTLV-III/LAV poses a transmission hazard, and the handling of such clothing is cov- ered under BSL 2 practices. However, to be consistent with BSL 3 recommendations (7), when laboratory clothing becomes contaminated with HTLV-III/LAV preparations, it should be decontaminated before being laundered or discarded. . Work surfaces should be decontaminated at the end of each day on completion of proce- dures or when overtly contaminated. Many commonly used chemical disinfectants with such active ingredients as sodium hypochlorite, formaldehyde, glutaraldehyde, or phenols (4,13-15) can be used to decontaminate laboratory work surfaces; they can also be used to decontaminate some laboratory instruments, specific areas of contaminated laboratory clothing, and spills of infectious materials. Prompt decontamination of spills and other overt contamination should be standard practice. . The prudent and recommended approach to handling human serum known or suspected to contain HTLV-III/LAV is to use the same precautions that should be used routinely to prevent transmission of bloodborne infections, including hepatitis B (76). Available data on the effectiveness of heat to destroy HTLV-III/LAV suspected or known to be present in human serum are at variance because of variations in volume of serum, concentration of the virus, temperature, and duration of exposure to heat (74,175,177). Similarly, results of chemical analyses or antibody assays may vary when sera are heated before testing ac- cording to the analysis or assay being performed (78-20). However, there is agreement that testing heated serum for HTLV-III/LAV antibody by enzyme immunoassays often yields false-positive results (27-23) . No HTLV-III/LAV vaccine has been developed, and no drugs have been shown to be safe and effective for therapy. As part of an ongoing medical surveillance program for employ- ees, all laboratory workers before being assigned to activities with a high potential for exposure should have a serum sample obtained and stored at -40 C (-40 F) for possible future testing. Subsequent serum samples should be obtained and stored in accordance with laboratory policy or following an inadvertent laboratory exposure involving materials described above. When indicated, these serum specimens should be tested by a qualified laboratory using currently recommended procedures for HTLV-III/LAV antibody. Further- more, the physician requesting serologic testing of these serum specimens must first obtain informed consent from the laboratory worker and describe the confidentiality safe- guards available to protect test results. The laboratory workers whose serum specimens are to be tested should understand how the test results are to be used, the implications of a positive or negative test result, and the limits, if any, of the confidentiality safeguards. An employee whose serum HTLV-lII/LAV antibody test is reactive and whose subsequent tests and evaluation confirm the presence of HTLV-III/LAV infection should be counseled to follow the Public Health Service recommendations for preventing transmission (24,25). P-30 9. In addition to HTLV-IIVLAV, other primary, as well as opportunistic, pathogenic agents may be present in the body fluids and tissues of persons who are antibody positive or have AIDS-related complex or AIDS. Laboratory workers should follow accepted biosafety prac- tices to ensure maximum protection against inadvertent laboratory infection with agents other than HTLV-III/LAV that may also be present in clinical specimens. Reported by Div of Safety, National Institute of Allergy and Infectious Diseases, National Cancer Inscitute, National Institutes of Health, AIDS Program, Hospital Infections Program, Center for Infectious Diseases, Laboratory Program Office, Office of Biosafety, Office of the Director, CDC. ADDENDUM CDC cautionary notice for all human serum samples used as controls or reagents: WARNING: Because no test method can offer complete assurance that laboratory specimens do not contain HTLV-III/LAV, hepatitis B virus, or other infectious agents, this specimen(s) should be handled at the BSL 2 as recommended for any potentially infectious human serum or blood specimen in the CDC-NIH manual, Biosafety in Microbiological and Biomedical Labo- ratories, 1984, pages 11-3. One or more of the following statements should be included with the above warning statement: This specimen is negative for hepatitis B surface antigen (HBsAg). This specimen is negative for antibody to HTLV -III/LAV. This specimen is positive for hepatitis B surface antigen (HBsAg). This specimen is positive for antibody to HTLV-IIlI/LAV. This specimen has NOT been tested for hepatitis B surface antigen (HBsAg). This specimen has NOT been tested for antibody to HTLV-III/LAV. This specimen has been heated at 56 C (133 F) for 30 minutes (which will not inactivate HBsAg but will inactivate HTLV-III/LAV). References 1 10. jt 12. 14 15 16 17 Richardson JH, Barkley WE, eds. Biosafety in microbiological and biomedical laboratories, 1984 Washington, DC: US Department of Health and Human Services, Public Health Service. HHS publi- cation no. (CDC) 84-8395. CDC. Update: evaluation of human T-lymphotropic virus type lll/lymphadenopathy-associated virus infection in health-care personnel — United States. MMWR 1985,34:575-8. CDC. Recommendations for preventing transmission of infection with human T-lymphotropic virus type lll/lymphadenopathy-associated virus in the workplace. MMWR 1985;34:682-6, 691-5. CDC. Acquired immune deficiency syndrome (AIDS): precautions for clinical and laboratory staffs MMWR 1982;32:577-80. CDC. Revision of the case definition of acquired immunodeficiency syndrome for national re- porting — United States. MMWR 1985,34:373-5. Weiss SH, Saxinger WC, Richtman D, et al. HTLV-IlIl infection among health care workers: associa- tion with needlestick injuries. JAMA 1985;254:2089-93. Anonymous. Needlestick transmission of HTLV-IIl from a patient infected in Africa. Lancet 1984; 1:1376-7. Henderson DK, Saah AJ, Zak BJ, et al. Risk of nosocomial infection with human T-cell lymphotropic virus type lll/lymphadenopathy-associated virus in a large cohort of intensively exposed health-care workers. Ann Intern Med 1986,104.644-7. Stricof RL, Morse DL. HTLV-II/LAV seroconversion following a deep intramuscular needlestick injury [Letter]. New Engl J Med 1986;314:1115. McCray E and the Cooperative Needlestick Surveillance Group. Occupational risk of the acquired immunodeficiency syndrome among health care workers. N Engl J Med 1986,314:1127-32. CDC. Classification system for human T-lymphotropic virus type Ill/lymphadenopathy-associated virus infections. MMWR 1986,35:334-9 U.S. Department of Health and Human Services, Public Health Service. Biosafety guidelines for use of HTLV-II and related viruses. Federal Register 1984, 49: Number 201, 40556. Favero MS. Sterilization, disinfection and antisepsis in the hospital. In: Lennette EH, Balows A, Haus- ler WJ,Jr, Shadomy HJ, eds. Manual of clinical microbiology. Washington, DC: American Society for Microbiology, 1985:129-37. Martin LS, McDougal JS, Loskoski SL. Disinfection and inactivation of the human T lymphotropic virus type lll/lymphadenopathy-associated virus. J Infect Dis 1985,;152:400-3. Resnick L, Veren K, Salahuddin, SZ, Tondreau S, Markham PD. Stability and inactivation of HTLV-IIl/ LAV under clinical and laboratory environments. JAMA 1986,255:1887-91 Favero MS, Petersen NJ, Bond WW. Transmission and control of laboratory-acquired hepatitis in- fection. In: Miller BM, Groschel DHM, Richardson JH, et al, eds. Laboratory safety: principles and practice. Washington, DC: American Society for Microbiology, 1986:49-58. Ronalds CJ, Grint PCA, Kangro HD. Disinfection and inactivation of HTLV-III/LAV [Letter] J Infect Dis 1986,153.996 P=31 20 21 22 23 24 28. Goldie DJ, McConnell AA, Cooke PR Heat treatment of whole blood and serum before chemical analysis [Letter] Lancet 1985:i 1161 Lai L, Ball G, Stevens J, Shanson D Effect of heat treatment of plasma and serum on biochemical indices [Letter] Lancet 1985;i:1457-8 Evans RP, Shanson DC. Effect of heat on serological tests for hepatitis B and syphilis and on amino- glycoside assays [Letter] Lancet 1985;i:1458 Van den Akker R, Hekker AC, Osterhaus ADME. Heat inactivation of serum may interfere witt. HTLV-III/LAV serology [Letter]. Lancet 1985;ii:672 Mortimer PP, Parry JV, Mortimer JY. Which anti-HTLV IlI/LAV assays for screening and confirma- tory testing? Lancet 1985;ii:873-7 Jungkind DL, DiRenzo SA, Young SJ. Effect of using heat-inactivated serum with the Abbott human T-cell lymphotropic virus type lll antibody test. J Clin Microbiol 1986,23:381-2 CDC. Prevention of acquired immune deficiency syndrome (AIDS): report of inter-agency recom- mendations. MMWR 1983;32:101-3 CDC. Additional recommendations to reduce sexual and drug abuse-related transmission of human T-lymphotropic virus type lll/lymphadenopathy-associated virus. MMWR 1986,35 152-5 P-32 Il. HEMOPHILIA PATIENTS 1984 Oct 26,33:589—-91 Update: Acquired Immunodeficiency Syndrome (AIDS) in Persons with Hemophilia Reports of hemophilia-associated acquired immunodeficiency syndrome (AIDS) in the United States were first published in July 1982 (7). Since then, the number of U.S. patients with underlying coagulation disorders who develop AIDS has increased each year. In 1981, one U.S. case was reported; in 1982, eight; in 1983, 14; and, as of October 15, 29 cases have been reported in 1984, for a total of 52 cases (Figure 1). Two of these 52 patients had hemophilia B; one, a factor V deficiency; and one, factor VIll deficiency due to her postpartum acquisition of a factor VIII inhibitor. The remaining 48 cases occurred among hemophilia A pa- tients. Three patients are known to have had risk factors for AIDS other than hemophilia. These 52 persons resided in 22 states. Only 10 states have reported more than one case, and no state has reported more than eight cases. With the exception of one 31-year-old factor V-deficient individual with Kaposi's sarcoma (and without risk factors for AIDS other than his hemophilia), each patient had at least one op- portunistic infection suggestive of an underlying cellular immune deficiency. Pneumocystis carinii pneumonia has been the most common opportunistic infection, occurring in 44 (85%) of the 52 patients. Other opportunistic infections have included toxoplasmic encephalitis (two cases), disseminated Mycobacterium avium intracellulare (one), disseminated cytomega- lovirus infection (two), disseminated candidiasis (one), and cryptococcal meningitis (one). Thirty hemophilia patients with AIDS have died; only three of the survivors were diagnosed more than 1 year ago. CDC has investigated the blood product usage of the majority of these cases. In nine cases, factor VIII concentrates have been the only blood product reportedly used in the 5 years before diagnosis of AIDS. These nine persons had no risk factors for AIDS other than hemophilia. The factor V-deficient patient with Kaposi's sarcoma had not used factor VIII con- centrate products but had used large volumes of plasma and factor IX concentrates. The sera of 22 (42%) of the 52 hemophilia-associated AIDS patients have been tested for antibody to antigens of the AIDS virus using Western blot analysis (2). Eighteen (82%) of these specimens contained antibody to one or more antigens (2,3). In cooperation with numerous hemophilia treatment centers and physicians, CDC has studied over 200 recipients of factor VIII and 36 recipients of factor IX concentrates containing materials from U.S. donors. Rates of AIDS virus antibody prevalence were 74% for factor VIII recipients and 39% for factor IX recipients (3,4). Only prospective evaluation will determine what risk of AIDS exists for seropositive individuals. A recently published study evaluated the thermostability of murine retroviruses inocculated into factor concentrates, using a cell transformation assay (5). After 48 hours at 68 C (154.4 F), viral titers dropped from 108 to two infectious particles/ml. In studies done at CDC, in cooperation with Cutter Laboratories, AIDS virus was added to factor VIIl concentrate (virus titer 10°) and the factor was lyophilized and heated to 68 C (154.4 F). The residual virus titer was determined by an infectivity assay (6). Virus was undetectable after 24 hours of heat treatment, the shortest time period examined. Reported by P Levine, MD, Medical Director, National Hemophilia Foundation, New York City, Div of Host Factors, Center for Infectious Diseases, COC. Editorial Note: The possibility of blood or blood products being vehicles for AIDS transmis- sion to hemophilia patients has been supported by the finding of risk of acquisition of AIDS for intravenous drug abusers (7) and, subsequently, by reports of transfusion-associated AIDS cases (8). The mainstays of therapy for the hemorrhagic phenomena of hemophilia are cryoprecipitate, fresh frozen plasma, and plasma factor preparations; these have been asso- ciated with the transmission of several known viral agents, including cytomegalovirus, hepati- tis B virus, and the virus(es) of non-A, non-B hepatitis (9). While many U.S. hemophilia- associated AIDS patients have received blood products other than factor concentrates in the 5 years preceding their AIDS diagnosis, the occurrence of nine cases with no known risk factor or exposure other than the use of factor VIII preparations implicates these products as potential vehicles of AIDS transmission. P-34 FIGURE 1. Hemophilia-associated acquired immunodeficiency syndrome (AIDS), by quar- ter — United States, 1981-October 15, 1984 i5y 14 13+ 12 + 11+ 101 CASES 0 T 1981 1982 1983 1984 QUARTER OF DIAGNOSIS The Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Founda- tion (NHF) has recently issued revised recommendations for the therapy of hemophilia (70). To physicians treating patients with hemophilia, they recommend that (1) cryoprecipitate be used in factor Vlll-deficient newborn infants and children under 4 years of age and in newly identified patients never treated with factor VIIl concentrates; (2) fresh frozen plasma be used in factor IX-deficient patients in the same categories; and (3) desmopressin (DDAVP) be used whenever possible in patients with mild or moderate hemophilia A. The majority of hemophilia patients do not fit in categories (1) through (3). For these patients, MASAC recommends that, “because heat-treated products appear to have no increase in untoward effects attributable to the heat treatment, treaters using coagulation factor concentrates should strongly consider changing to heat-treated products with the understanding that protection against AIDS is yet to be proven.” They also recommend that all elective surgical procedures for hemophilia pa- tients be evaluated with respect to possible advantages and disadvantages of surgical delays. Although the total number of hemophilia patients who have thus far developed clinical manifestations of AIDS is small relative to other AIDS risk groups, incidence rates for this group are high (3.6 cases/1,000 hemophilia A patients and 0.6/1,000 hemophilia B patients). Continued surveillance is important. Physicians diagnosing opportunistic infections or unusual neoplasms in hemophilia patients who have not received antecedent immunosuppressive therapy are requested to report these findings to local or state health departments and to CDC. In March 1983, the U.S. Public Health Service recommended that members of groups at increased risk of acquiring AIDS should refrain from donating plasma and/or blood (77). A specific serologic test will soon become available for screening purposes, and thus a safer factor concentrate product should result. The preliminary evidence concerning the effects of heat-treatment on the viability of the AIDS virus is strongly supportive of the usefulness of heat-treatment in reducing the potential for transmission of the AIDS virus in factor concen- trate products and suggest that the use of nonheat-treated factor concentrates should be limited. CDC and NHF will continue to study the effects of heat-treated factor on the immune status of patients with hemophilia. References 1. CDC. Pneumocystis carinii pneumonia among persons with hemophilia A. MMWR 1982;31:365-7 2. Tsang VC, Peralta JM, Simons AR. Enzyme-linked immunoelectrotransfer blot techniques (EITB) for studying the specificities of antigens and antibodies separated by gel electrophoresis. Methods Enzymol 1983;92:377-91 3. Ramsey RB, Palmer EL, McDougal JS, et al. Antibody to lymphadenopathy-associated virus in hae- mophiliacs with and without AIDS. Lancet [Letter] 1984;11:397-8 P-35 CDC Unpublished data Levy JA, Mitra G, Mozen MM Recovery and inactivation of infectious retroviruses from factor VIII concentrates Lancet 1984 11 722-3 McDougal JS, Cort SP, Kennedy MS, et al. Immunology for the detection and quantitation of infec- tious human retrovirus, lymphadenopathy-associated virus (LAV). J Immunol Methods (in press) Spira TJ, Des Jarlais DC, Marmor M, et al. Prevalence of antibody to lymphadenopathy-associated virus among drug-detoxification patients in New York. N Engl J Med [Letter] 1984,311 467-8 Curran JW, Lawrence DN, Jaffe H, et al. Acquired immunodeficiency syndrome (AIDS) associated with transfusions. N Engl J Med 1984,310:69-75. Enck RE, Betts RF, Brown MR, Miller G. Viral serology (hepatitis B virus, cytomegalovirus, Epstein- Barr virus) and abnormal liver function tests in transfused patients with hereditary hemorrhagic dis- eases. Transfusion 1979,19 32-8 National Hemophilia Foundation Medical and Scientific Advisory Council. Recommendations con- cerning AIDS and therapy of hemophilia (revised October 13, 1984). New York: National Hemophi- lia Foundation, 1984 CDC. Prevention of acquired immune deficiency syndrome (AIDS) report of interagency recom- mendations MMWR 1983,32 101-3 IV. PATIENTS WITH SPECIAL DISEASE CONDITIONS 1986 June 13;35:376—-83 Recommendations for Providing Dialysis Treatment to Patients Infected with Human T-Lymphotropic Virus Type lll/Lymphadenopathy-Associated Virus Patients with end-stage renal disease who are unde, going maintenance dialysis and who have manifestations of human T-lymphotropic virus type lll/lymphadenopathy-associated virus (HTLV-III/LAV)* infection, including acquired immunodeficiency syndrome (AIDS), or who are positive for anfibody to HTLV-III/LAV can be dialyzed in hospital-based or free-standing di- alysis units using conventional infection-control precautions. Standard blood and body fluid precautions and disinfection and sterilization strategies routinely practiced in dialysis centers are adequate to prevent transmission of HTLV-III/LAV. Soon after AIDS was recognized in the United States, it became apparent that risk factors for persons with AIDS were similar to risk factors for persons with hepatitis B virus (HBV) infec- tion (7). Prevention measures applied to control HBV infection in health-care institutions were used as a model to develop infection-control guidelines for patients with AIDS before the iden- tification of the etiologic agent and the development of serologic tests for antibody to HTLV-IIl/ LAV (anti-HTLV-IIl). Isolation of infected patients and nonreuse of a dialyzer by the same patient were initially recommended for patients receiving dialysis in dialysis centers (2). These strate- gies are not currently believed necessary for preventing HTLV-III/LAV transmission. No transmission of HTLV-III/LAV infection in the dialysis-center environment has been reported (3), and the possibility of such transmission appears extremely unlikely when routine infection-control precautions are followed (4). The routine infection-control precautions used in all dialysis centers when dialyzing all patients are considered adequate to prevent HTLV-IIl/ LAV transmission. These would include: blood precautions; routine cleaning and disinfection of dialysis equipment and surfaces that are frequently touched; and restriction of nondispos- able supplies to individual patients unless such supplies are sterilized between uses (2). The following recommendations take into consideration recent knowledge about HTLV-IIl/ LAV and update infection-control strategies for dialyzing patients infected with HTLV-IlI/LAV: 1. Procedures for environmental control and for disinfection and sterilization of hemodi- alysis machines have been described (5). The hemodialysis machine pumps dialysis fluid into the dialyzer (artificial kidney) where circulating blood from the patient is separated from the dialysis fluid by a membrane. The dialyzer, along with the associat- ed blood lines, is disposable. Strategies for disinfecting the dialysis fluid pathways of the hemodialysis machine are targeted to control bacterial contamination and generally consist of using about 500-750 ppm of sodium hypochlorite for 30-40 minutes or 1.5%-2.0% formaldehyde overnight. In addition, several chemical germicides formulated to disinfect dialysis machines are commercially available. None of these protocols or procedures need to be altered after dialyzing patients infected with HTLV-III/LAV. Chemical germicides used for disinfection and sterilization of devices in the dialysis center are effective against HTLV-III/LAV (4). 2. Patients infected with HTLV-lII/LAV can be dialyzed by either hemodialysis or peritoneal dialysis and do not need to be isolated from other patients. The type of dialysis treat- ment (i.e., hemodialysis or peritoneal dialysis) should be based on the needs of the pa- tient. The dialyzer may be discarded after each use. Alternatively, centers that have dialyzer-reuse programs, in which a specific dialyzer is issued to a specific patient, re- moved, cleaned, disinfected, and reused several times on the same patient only, may in- clude HTLV-III/LAV-infected patients in the dialyzer-reuse program. An individual dialyz- er must never be used on more than one patient. 3. Standard infection-control strategies that are used routinely in dialysis units for all dialy- sis patients and personnel should be used to prevent HTLV-lII/LAV transmission. Spe- cifically, these strategies include blood precautions and barrier techniques, such as the use of gloves, gowns, and handwashing techniques, that have been described else- where (4-8). “An international committee on taxonomy has proposed the name human immunodeficiency virus (HIV). pP-38 4. Precautions against needlestick injuries, as well as the appropriate use of barrier precau- tions, such as wearing gloves when handling items contaminated with blood or serum, should be practiced by all personnel caring for all dialysis patients. Such injuries consti- tute the major potential risk for HTLV-III/LAV transmission to personnel. Extraordinary care should be taken to prevent injuries to hands caused by needles, scalpels, and other sharp instruments or devices during procedures; when cleaning used instruments; during disposal of used needles; and when handling sharp instruments following procedures. After use, disposable syringes and needles, scalpel blades, and other sharp items must be placed in puncture-resistant containers for disposal. To prevent needlestick injuries, nee- dles should not be recapped; purposefully bent or broken; removed from disposable sy- ringes; or otherwise manipulated by hand. No data are currently available from controlled studies examining the effect, if any, of the use of needle-cutting devices on the incidence of needlestick injuries. Reported by Hospital Infections Program, AIDS Program, Center for Infectious Diseases, COC. Editorial Note: In a study of 520 dialysis patients, 25 were reactive for anti-HTLV-IlI/LAV by enzyme immunoassay (EIA), but only four were confirmed by the Western blot technique (3). The rate of falsely reactive EIA tests among these dialysis patients was 4%, much higher than the falsely reactive rate for blood donors (0.17%). The rate of truly reactive tests was 0.8%, much lower than in high-risk groups but higher than in blood donors. The higher rate of falsely reactive tests is probably due to the exposure of dialysis patients to H9-cell-associated anti- gens during blood transfusions that are common among these patients. These antigens are also present in cell lines used to grow HTLV-III/LAV for use as reagents in serologic tests for anti-HTLV-III/LAV (9). Identification of antibody to H9 lymphoid cell lines in the absence of isolation of HTLV-HII/LAV in dialysis patients with reactive EIA and nonreactive Western blot tests supports the conclusion that these test results are falsely reactive. The higher rate of truly reactive tests most likely reflects the frequency of blood transfusion in this patient popu- lation before initiation of blood donor screening for anti-HTLV-III/LAV. None of the four infect- ed persons identified in that study were dialyzed in the same dialysis center. CDC is initiating a cooperative study to further assess the prevalence of anti-HTLV-IIlI/LAV among patients undergoing chronic hemodialysis. Representatives of dialysis centers who are interested in participating in such a study and who regularly have more than 60 patients on di- alysis shouid contact the Hospital Infections Program, Center for Infectious Diseases, CDC, Building 1, Room 5065, Atlanta, Georgia 30333 (telephone [404] 329-3406). References 1. Curran JW, Evatt BL, Lawrence DN. Acquired immune deficiency syndrome: the past as prologue. Ann Intern Med 1983;98:401-2. 2. Favero MS. Recommended precautions for patients undergoing hemodialysis who have AIDS or non-A, non-B hepatitis. Infect Control 1985;6:301-5. 3. Peterman TA, Lang GR, Mikos NJ, et al. HTLV-III/LAV infection in hemodialysis patients. JAMA 1986,255:2324-6. 4. CDC. Summary: recommendations for preventing transmission of infection with human T-lympho- tropic virus type lll/lymphadenopathy-associated virus in the workplace. MMWR 1985;34:681. 5. Favero MS. Dialysis-associated diseases and their control. In: Bennett JV, Brachman PS, eds. Hospital infections. Boston: Little, Brown and Company, Inc., 1985:267-84. 6. CDC. Hepatitis — control measures for hepatitis B in dialysis centers. Viral hepatitis: Atlanta, Georgia: Center for Disease Control, 1977: HEW publication no. (CDC)78-8358 (Investigation and control series, November 1977). 7. CDC. Hepatitis surveillance report no. 49. Issued January 1985:3-4. 8. Garner JS, Simmons BP. CDC guideline for isolation precautions in hospitals. Infect Control 1983.5: 245-325. 9. CDC. Update: Public Health Service workshop on human T-lymphotropic virus type lll antibody testing — United States. MMWR 1985;34:477-8. 1986 July 18,;35:448-52 Diagnosis and Management of Mycobacterial Infection and Disease in Persons with Human T-Lymphotropic Virus Type Ill/ Lymphadenopathy-Associated Virus Infection In 1985, the number of new tuberculosis cases reported to CDC was essentially the same as that reported in 1984 (7). In contrast, the average annual decline in morbidity during the past 32 years has been 5%. The failure of tuberculosis morbidity to decline as expected in 1985 is probably related to the occurrence of tuberculosis among persons with acquired im- munodeficiency syndrome (AIDS) or human T-lymphotropic virus type lll/lymphadenopathy- associated virus (HTLV/LAV)® infection. Several reports have indicated that mycobacterial disease is common among AIDS patients and among persons at risk for AIDS (2-9). The most common mycobacterial species isolated from patients with diagnosed AIDS is Myco- bacterium avium complex (MAC), although in some groups in which tuberculous infection is highly prevalent, disease caused by M. tuberculosis is more common (70-72). Even among groups in which MAC is the most common mycobacterial pathogen, M. tuberculosis accounts for a substantial proportion of the mycobacterial isolates. The association between myco- bacterial disease and AIDS raises several important clinical and public health issues that are addressed below. DIAGNOSIS OF TUBERCULOSIS IN PATIENTS LIKELY TO HAVE HTLV-III/LAV INFECTION Clinicians should consider the diagnosis of tuberculosis in patients with, or at risk of, HTLV-HII/LAV infection, even if the clinical presentation is unusual (4, 73,74). Available data indicate that extrapulmonary forms of tuberculosis, particularly lymphatic and disseminated (miliary), are seen much more frequently among patients with HTLV-IlI/LAV infection than among those without such infection. Pulmonary tuberculosis in patients with HTLV-HII/LAV in- fection cannot readily be distinguished from other pulmonary infections, such as Pneumocys- tis carinii pneumonia, on the basis of clinical and radiographic findings. Patients with tuber- culosis may have infiltrates in any lung zone, often associated with mediastinal and/or hilar lymphadenopathy. Cavitation is uncommon. Appropriate specimens to establish a culture- confirmed diagnosis of tuberculosis include respiratory secretions, urine, blood, lymph node, bone marrow, liver, or other tissue or body fluid that is indicated clinically. All tissue specimens should be stained for acid-fast bacilli and cultured for mycobacteria. In the presence of undi- agnosed pulmonary infiltrates, bronchoscopy with lavage and transbronchial biopsy (if-not contraindicated) may be needed to obtain material for both culture and histologic examination. A tuberculin skin test should be administered, but the absence of a reaction does not rule out the diagnosis of tuberculosis because immunosuppression associated with HTLV-III/LAV in- fection may cause false-negative results. TREATMENT OF MYCOBACTERIAL DISEASE IN A PATIENT WITH HTLV-II/LAV INFECTION Chemotherapy should be started whenever acid-fast bacilli are found in a specimen from a patient with HTLV-1II/LAV infection and clinical evidence of mycobacterial dis- ease. Because it is difficult to distinguish tuberculosis from MAC disease by any criterion other than culture, and because of the individual and public health implications of tuberculosis, it is important to treat patients with a regimen effective against tuberculosis. With some ex- ceptions, patients with tuberculosis and HTLV-II/LAV infection respond relatively well to standard antituberculosis drugs (75); however, their treatment should include at least three drugs initially, and treatment may need to be longer than the standard duration of 9 months (76). The recommended regimen is isoniazid (INH), 10-15 mg/kg/day up to 300 mg/day; rifampin (RIF), 10-15 mg/kg/day up to 600 mg/day; and either ethambutol (EMB), 25 mg/ kg/day, or pyrazinamide (PZA), 20-30 mg/kg/day. The last two drugs are usually given only during the first 2 months of therapy. The addition of a fourth drug may be indicated in certain situations, such as central nervous system or disseminated disease or when INH resistance is suspected. An initial drug-susceptibility test should always be performed, and the treatment regimen, revised if resistance is found to any of the drugs being used. The appropriate dura- tion of treatment for patients with tuberculosis and HTLV-III/LAV infection is unknown; how- ever, it is recommended that treatment continue for a minimum of 9 months and for at least 6 ‘The Human Retrovirus Subcommittee of the International Committee on the Taxonomy of Viruses has proposed the name human immunodeficiency virus (HIV) for this virus (Science 1986,232:697) P-40 months after documented culture conversion If INH or RIF is not included in the treatment regimen, therapy should continue for a minimum of 18 months and for at least 12 months fol- lowing culture conversion. After therapy is completed, patients should be followed closely, and mycobacteriologic examinations should be repeated if clinically indicated. Some clinicians would take a different approach to treatment than that outlined above, to cover the possibility of MAC disease. Although the clinical significance and optimal therapy of MAC disease in these patients is not well defined, and there are no definitive data on the ef- ficacy of treatment, one regimen commonly used to treat MAC disease substitutes rifabutin (ansamycin LM 427) for rifampin, combined with INH, EMB, and clofazimine. Rifabutin and clofazimine are experimental drugs available to qualified investigators only under investiga- tional new drug protocols. Rifabutin is distributed by the CDC Drug Service (telephone: [404] 329-3670), and clofazimine, by Ciba-Geigy: (telephone: [201] 277-5787). If M. tuberculosis is isolated from a patient receiving this four-drug regimen, treatment should be switched to one of the three-drug regimens outlined above (INH, RIF, and EMB or PZA). If MAC is isolated from a patient who has been started on a three-drug regimen, the clinician may continue the three-drug regimen or switch to the four-drug regimen of INH, EMB, rifabutin, and clofazimine. Although experience is very limited, patients with disease due to M. kansasii should re- spond to INH, RIF, and EMB. Some clinicians advocate the addition of streptomycin (SM), 1 gram twice weekly, for the first 3 months. Therapy should continue for a minimum of 15 months following culture conversion. Monitoring for toxicity of antimycobacterial drugs may be difficult for patients who may: be receiving a variety of other drugs and may have other concomitant conditions. Because hepatic and hematologic abnormalities may be caused by the mycobacterial disease, AIDS, or other drugs and conditions, the presence of such abnormalities is not an absolute contraindi- cation to the use of the treatment regimens outlined above. INFECTION CONTROL Recommendations for preventing transmission of HTLV-III/LAV infection to health-care workers have been published (7 7). In addition, infection-control procedures applied to patients with HTLV-III/LAV infection who have undiagnosed pulmonary disease should always take the possibility of tuberculosis into account. This is especially true when diagnostic procedures, such as sputum induction or bronchoscopy, are being performed. Previously published guide- lines for preventing tuberculosis transmission in hospitals should be followed (78). CONTACT INVESTIGATION FOR TUBERCULOSIS Patients with pulmonary tuberculosis and HTLV-III/LAV infection should be considered potentially infectious for tuberculosis, and standard procedures for tuberculosis contact in- vestigation should be followed (79). Specific data on the infectiousness of tuberculosis in pa- tients with HTLV-III/LAV infection are not yet available. EXAMINING HTLV-III/LAV-INFECTED PERSONS FOR TUBERCULOSIS AND TUBERCU- LOUS INFECTION Individuals who are known to be HTLV-IlI/LAV seropositive should be given a Mantoux skin test with 5 tuberculin units of purified protein derivative as part of their clinical evaluation. Although some false-negative skin test results may be encountered in this setting as a result of immunosuppression induced by HTLV-III/LAV infection, significant reactions are still mean- ingful (20). If the skin test reaction is significant, a chest radiograph should be obtained, and if abnormalities are detected, additional diagnostic procedures for tuberculosis should be un- dertaken. Patients with clinical AIDS or other Class IV HTLV-III/LAV infections (27) should re- ceive both a tuberculin skin test and a chest radiograph because of the higher probability of false-negative tuberculin reactions in immunosuppressed patients. EXAMINING PATIENTS WITH CLINICALLY ACTIVE TUBERCULOSIS OR LATENT TUBERCULOUS INFECTION FOR HTLV-HI/LAV INFECTION As part of the evaluation of patients with tuberculosis and tuberculous infection, risk fac- tors for HTLV-II LAV should be identified. Voluntary testing of all persons with these risk fac- tors is recommended (22). In addition, testing for HTLV-III/LAV antibody should be consid- ered for patients of all ages who have severe or unusual manifestations of tuberculosis. The presence of HTLV-III/LAV infection has implications regarding treatment (see above), alerts the physician to the possibility of other opportunistic infections, and allows for counselling about transmission of HTLV-III/LAV infection (23). Testing for HTLV-III/LAV antibody is espe- cially important for persons over age 35 with asymptomatic tuberculous infection, because INH would not usually be indicated for persons in this age group unless they are also HTLV-Ill/ LAV seropositive. P-41 PREVENTIVE THERAPY HTLV-II/LAV seropositivity in a person of any age with a significant tuberculin reaction is an indication for INH preventive therapy (76). Although it is not known whether INH therapy is as efficacious in preventing tuberculosis in HTLV-III/LAV-infected persons as in other groups, the usually good response of HTLV-III/LAV-infected persons with tuberculosis to standard therapy suggests that INH preventive therapy would also be effective. Before in- stituting preventive therapy, clinically active tuberculosis should be excluded. Developed by Center for Prevention Svcs, Center for Infectious Diseases, COC, with consultation from RS Holzman, MD, New York University Medical Center, New York City, PC Hopewell MD, San Francisco General Hospital Medical Center, California, AE Pitchemk, MD, University of Miami: Medical Center, Flor:- da; LB Reichman, MD, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, University Hospital, Newark, New Jersey, RL Stoneburner, MD, New York City Dept of Health References 1. CDC. Tuberculosis—United States, 1985—and the possible impact of human T-lymphotropic virus type lll/lymphadenopathy-associated virus infection MMWR 1986.35 74-6 2. Cohen RJ, Samoszuk MK, Busch D. Lagios M [Letter] Occult infections with M intracellulare n bone-marrow biopsy specimens from patients with AIDS N Engl J Med 1983,308 1475-6 3. Wong B, Edwards FF, Kiehn TE, et al. Continuous high-grade Mycobacterium avium-intracellulare bacteremia in patients with the acquired immunodeficiency syndrome Am J Med 1985,78 35-40 4 Pitchenik AE, Cole C, Russell BW, Fischl MA, Spira TJ, Sruder DE, Jr Tuberculosis, atypical myco- bacteriosis, and the acquired immunodeficiency syndrome among Haitian and non-Haitian patients in south Florida. Ann Intern Med 1984,101.641-5 5 Macher AM, Kovacs JA, Gill V, et al Bacteremia due to Mycobacterium avium-intracellulare in the acquired immunodeficiency syndrome. Ann Intern Med 1983,99 782-5 6. Zakowski P, Fligiel S, Berlin GW, Johnson L, Jr. Disseminated Mycobacterium avium-intracellulare infection in homosexual men dying of acquired immunodeficiency. JAMA 1982,248 2980-2 7. Greene JB, Sidhu GS, Lewis S, et al Mycobacterium avium-intracellulare a cause of disseminated life-threatening infection in homosexuals and drug abusers. Ann Intern Med 1982,97 539-46 8 Chan J, McKitrick JC, Klein RS. Mycobacterium gordonae wn the acquired immunodeficiency syn- drome [Letter] Ann Intern Med 1984,101 400 9. Eng RH, Forrester C, Smith SM, Sobel H Mycobacterium xenop: infection in a patient with acquired immunodeficiency syndrome. Chest 1984 ,86:145-7 10. Pape JW, Liautaud B, Thomas F, et al. Characteristics of the acquired immunodeficiency syndrome (AIDS) in Haiti N Eng J Med 1983,309 945-50 11. Maayan S, Wormser GP, Hewlett D, et al Acquired immunodeficiency syndrome (AIDS) in an eco- nomically disadvantaged population Arch Intern Med 1985,145 1607-12 12 Goedert JJ, Weiss SH, Biggar RJ, et al Lesser AIDS and tuberculosis [Letter] Lancet 1985 1 52 13 Sunderam G, Maniatis T, Kapila R, et al Mycobacterium tuberculosis disease with unusual manifes- tations is relatively common in acquired immuno-deficiency syndrome (AIDS) [Abstract] Am Rev Resp Dis 1984129 (part 2) A191 14 Pitchenik AE, Rubinson HA The radiographic appearance of tuberculosis in patients with the ac- quired immune deficiency syndrome (AIDS) and pre-AIDS Am Rev Resp Dis 1985,131 393-6 15 Sunderam G, McDonald RJ, Maniatis T, Oleske J, Kapila R, Reichman LB Tuberculosis as a manifes- tation of the acquired immunodeficiency syndrome (AIDS) JAMA 1986,256 357-61 16 American Thoracic Society Treatment of tuberculosis and other mycobactenal diseases Am Rev Resp Dis 1983,127 790-6 17. CDC. Recommendations for preventing transmission of infection with human T-lymphotropic virus type Ill/lymphadenopathy-associated virus in the workplace. MMWR 1985;34:681-95. 18. CDC. Guidelines for prevention of TB transmission in hospitals. Atlanta, Georgia: U.S. Department of Health and Human Services, 1982: HHS publication no. (CDC) 82-8371. 19. American Thoracic Scciety/CDC. Control of tuberculosis. Am Rev Resp Dis 1983,128:336-42. 20. American Thoracic Society. The tuberculin skin test. Am Rev Resp Dis 1981,124:356-63. 21. CDC. Classification system for human T-lymphotropic virus type lll. lymphadenopathy-associated virus infections. MMWR 1986,35:334-9. 22. CDC. Additional recommendations to reduce sexual and drug abuse-related transmission of human T-lymphotropic virus type lli/lympadenopathy-associated virus. MMWR 1986,35.152-5. 23. CDC. Human T-lymphotropic virus type Ill/lymphadenopathy-associated virus antibody testing at alternate sites. MMWR 1986,35:284-7. V. DONORS OF BODY FLUIDS AND TISSUES 1985 Jan 11:34:1-5 Provisional Public Health Service Inter-Agency Recommendations for Screening Donated Blood and Plasma for Antibody to the Virus Causing Acquired Immunodeficiency Syndrome In March 1983, the U.S. Public Health Service issued inter-agency recommendations on the prevention of acquired immunodeficiency syndrome (AIDS) (7). Included was the recom- mendation that members of groups at increased risk for AIDS should refrain from donating plasma and/or blood. That recommendation was made to decrease the risk of AIDS associat- ed with the administration of blood or blood products, which accounts for about 2% of all reported AIDS cases in the United States. Evidence has shown that a newly recognized retrovirus is the cause of AIDS. Although this virus has been given several names, including human T-lymphotropic virus type lll (HTLV-II) (2), lymphadenopathy-associated virus (LAV) (3), and AIDS-associated retrovirus (ARV) (4), it is referred to as HTLV-II in this discussion. Tests to detect antibody to HTLV-II will’ be licensed and commercially available in the United States in the near future to screen blood and plasma for laboratory evidence of infection with the virus. The antibody tests are modifi- cations of the enzyme-linked immunosorbent assay (ELISA), which uses antigens derived from whole disrupted HTLV-II (5). There is considerable experience with the ELISA test in research laboratories, but much additional information will be gathered following its widespread application. In the early phases of testing, a number of false-positive tests may be encountered. Adjustments in inter- pretation are anticipated as more is learned about the performance of the test in an individual laboratory and about the specific proportion of falsely positive or falsely negative tests in the screening setting where the test is used. The present recommendations concern the use of these tests to screen blood and plasma collected for transfusion or manufactured into other products. They are intended to supple- ment, rather than replace, the U.S. Food and Drug Administration's recently revised recom- mendations to blood and plasma collection facilities and the earlier inter-agency recommen- dations (7). Additional public health applications of these tests in the understanding and con- trol of AIDS will be described in a subsequent report. BACKGROUND Antibody Detection Studies The ELISA test has been used in many research programs for detecting antibodies to HTLV-II in patients with AIDS and with AIDS-related conditions. In different studies, HTLV-II antibody was found to range from 68% to 100% of patients with AIDS, and in 84%-100% of persons with related conditions, such as unexplained generalized lymphadenopathy (5-7). Serologic surveys have yielded variable seropositivity rates in groups at increased risk for AIDS: 22%-65% of homosexual men (8-717), 87% of intravenous-drug abusers admitted to a detoxification program in New York City (72), 56%-72% of persons with hemophilia A (13,14), and 35% of women who were sexual partners of men with AIDS (75). In contrast to the above groups, HTLV-II antibody has been detected in fewer than 1% of persons with no known risks for AIDS (4-70). The time needed to develop a positive antibody test following infection is not known. Data regarding the interval between infection with HTLV-Ill and seroconversion are limited. A nurse who sustained a needle-stick injury while caring for an AIDS patient developed antibody be- tween 4 and 7 weeks following exposure (76). Additionally, a recent study described several asymptomatic individuals infected with HTLV-II for more than 6 months in the absence of detectable antibody (77,78). Nonetheless, currently available ELISA tests can be expected to identify most persons with HTLV-Ill infection. Virus Isolation Studies HTLV-II has been isolated from blood, semen, and saliva and has been recovered from many individuals in the presence of antibody (79,20). HTLV-II has been isolated from the blood of 85% or more of seropositive individuals with AIDS (27), lymphadenopathy, or other AIDS-associated conditions (2) and from three of four mothers of infants with AIDS (2). The virus has also been isolated from asymptomatic seropositive homosexual men and hemophil- iacs, and has been recovered from 95% of seropositive high-risk blood donors who had been P-44 implicated in the transmission of AIDS through transfusion (27). The recovery of HTLV-II from these high-risk donors 2 or more years after their initial donation provides evidence that viremia may persist for years in both asymptomatic and symptomatic individuals. HTLV-II has also been isolated from some asymptomatic seronegative persons, but this is the excep- tion (77). Modes of Transmission Epidemiologic data suggest that the virus has been transmitted through intimate sexual contact; sharing contaminated needles; transfusion of whole blood, blood cellular compo- nents, plasma, or clotting factor concentrates that have not been heat treated; or from infect- ed mother to child before, at, or shortly after the time of birth. No other products prepared from blood (e.g., immunoglobulin, albumin, plasma protein fraction, hepatitis B vaccine) have been implicated, nor have cases been documented to occur through such common exposures as sharing meals, sneezing or coughing, or other casual contact. Natural History of Infection Information about the course of infection with HTLV-Ill is incomplete, but the majority of infected adults will not acquire clinically apparent AIDS in the first few years after infection. In some studies 5%-19% of seropositive homosexual men developed AIDS within 2-5 years after a previously collected serum sample was retrospectively tested and found to be sero- positive. An additional 25% developed generalized lymphadenopathy, oral candidiasis, or other AIDS-associated conditions within the same interval (77,22). The long-term prognosis for most persons infected with HTLV-II is unknown. SCREENING BLOOD AND PLASMA Initial Testing Persons accepted as donors should be informed that their blood or plasma will be tested for HTLV-II antibody. Persons not wishing to have their blood or plasma tested must refrain from donation. Donors should be told that they will be notified if their test is positive and that they may be placed on the collection facility's donor deferral list, as is currently practiced with other infectious diseases, and should be informed of the identities of additional deferral lists to which the positive donors may be added. All blood or plasma should be tested for HTLV-II antibody by ELISA. Any blood or plasma that is positive on initial testing must not be transfused or manufactured into other products capable of transmitting infectious agents. When the ELISA is used to screen populations in whom the prevalence of HTLV-II infec- tions is low, the proportion of positive results that are falsely positive will be high. Therefore, the ELISA should be repeated on all seropositive specimens before the donor is notified. If the repeat ELISA test is negative, the specimen should be tested by another test. Other Testing Other tests have included immunofluorescence and radioimmunoprecipitation assays, but the most extensive experience has been with the Western blot technique (22), in which an- tibodies can be detected to HTLV-Ill proteins of specific molecular weights. Based on available data, the Western blot should be considered positive for antibody to HTLV-II if band p24 or gp41 is present (alone or in combination with other bands). Notification of Donors If the repeat ELISA test is positive or if other tests are positive, it is the responsibility of the collection facility to ensure that the donor is notified. The information should be given to the donor by an individual especially aware of the sensitivities involved. At present, the proportion of these seropositive donors who have been infected with HTLV-Ill is not known. It is, there- fore, important to emphasize to the donor that the positive result is a preliminary finding that may not represent true infection. To determine the significance of a positive test, the donor should be referred to a physician for evaluation. The information should be given to the donor in a manner to ensure confidentiality of the results and of the donor's identify. Maintaining Confidentiality Physicians, laboratory and nursing personnel, and others should recognize the importance of maintaining confidentiality of positive test results. Disclosure of this information for pur- poses other than medical or public health could lead to serious consequences for the individu- al. Screening procedures should be designed with safeguards to protect against unauthorized disclosure. Donors should be given a clear explanation of how information about them will be handled. Facilities should consider developing contingency plans in the event that disclosure is sought through legal process. If donor deferral lists are kept, it is necessary to maintain con- fidentiality of such lists. Whenever appropriate, as an additional safeguard, donor deferral lists should be general, without indication of the reason for inclusion. Medical Evaluation The evaluation might include ELISA testing of a follow-up serum specimen and Western blot testing, if the specimen is positive. Persons who continue to show serologic evidence of HTLV-II infection should be questioned about possible exposure to the virus or possible risk factors for AIDS in the individual or his/her sexual contacts and examined for signs of AIDS or related conditions, such as lymphadenopathy, oral candidiasis, Kaposi's sarcoma, and unex- plained weight loss. Additional laboratory studies might include tests for other sexually trans- mitted diseases, tests of immune function, and where available, tests for the presence of the virus, such as viral culture. Testing for antibodies to HTLV-lIl in the individual's sexual contacts may also be useful in establishing whether the test results truly represent infection. RECOMMENDATIONS FOR THE INDIVIDUAL An individual judged most likely to have an HTLV-Ilil infection should be provided the fol- lowing information and advice: 1. The prognosis for an individual infected with HTLV-lIl over the long term is not known. However, data available from studies conducted among homosexual men indicate that most persons will remain infected. 2. Although asymptomatic, these individuals may transmit HTLV-Ill to others. Regular medical evaluation and follow-up is advised, especially for individuals who develop signs or symptoms suggestive of AIDS. 3. Refrain from donating blood, plasma, body organs, other tissue, or sperm. 4. There is a risk of infecting others by sexual intercourse, sharing of needles, and possi- bly, exposure of others to saliva through oral-genital contact or intimate kissing. The efficacy of condoms in preventing infection with HTLV-II is unproven, but the consis- tent use of them may reduce transmission. 5. Toothbrushes, razors, or other implements that could become contaminated with blood should not be shared. 6. Women with a seropositive test, or women whose sexual partner is seropositive, are themselves at increased risk of acquiring AIDS. If they become pregnant, their offspr- ing are also at increased risk of acquiring AIDS. 7. After accidents resulting in bleeding, contaminated surfaces should be cleaned with household bleach freshly diluted 1:10 in water. 8. Devices that have punctured the skin, such as hypodermic and acupuncture needles, should be steam sterilized by autoclave before reuse or safely discarded. Whenever possible, disposable needles and equipment should be used. 9. When seeking medical or dental care for intercurrent illness, these persons should inform those responsible for their care of their positive antibody status so that ap- propriate evaluation can be undertaken and precautions taken to prevent transmission to others. 10. Testing for HTLV-II antibody should be offered to persons who may have been infect- ed as a result of their contact with seropositive individuals (e.g., sexual partners, per- sons with whom needles have been shared, infants born to seropositive mothers). Revised recommendations will be published as additional information becomes available and additional experience is gained with this test. Reported by Centers for Disease Control; Food and Drug Administration, Alcohol, Drug Abuse, and Men- tal Health Administration; National Institutes of Health; Health Resources and Services Administration. References 1. CDC. Prevention of acquired immune deficiency syndrome (AIDS): Report of inter-agency recom- mendations. MMWR 1983; 32:101-3. 2. Gallo RC, Salahuddin SZ, Popovic M, et al. Frequent detection and isolation of cytopathic retrovi- ruses (HTLV-II) from patients with AIDS and at risk for AIDS. Science 1984;224:500-3. 3. Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983,220:868-71. 4. Levy JA, Hoffman AD, Kramer SM, Landis JA, Shimabukuro JM, Oschiro LS. Isolation of lymphocy- topathic retroviruses from San Francisco patients with AIDS. Science 1984;225:840-2. 5. Sarngadharan MG, Popovic M, Bruch L, Schupbach J, Gallo RC. Antibodies reactive with human T- lymphotropic retroviruses (HTLV-lil) in the serum of patients with AIDS. Science 1984,224-506-8. 6. Safai B, Sarngadharan MG. Groopman JE, et al. Seroepidemiological studies of human T- lymphotropic retrovirus type lll in acquired immunodeficiency syndrome. Lancet 1984;1:1438-40. 7. Laurence J, Brun-Vezinet F, Schutzer SE, et al. Lymphadenopathy associated viral antibody in AIDS. N Engl J Med 1984,311:1269-73 8. Melbye M, Biggar RJ, Ebbesen P, et al. Seroepidemiology of HTLV-II antibody in Danish homosexu- al men: prevalence, transmission, and disease outcome. Brit Med J 1984; 289:573-5. 9. CDC. Antibodies to a retrovirus etiologically associated with acquired immunodeficiency syndrome (AIDS) in populations with increased incidences of the syndrome. MMWR 1984; 33:377-9. 10. Weiss SH, Goedert JJ, Sarngadharan MB, et al. Screening test for HTLV-II (AIDS agent) antibodies: specificity, sensitivity, and applications. JAMA 1985; 253:221-5. P-46 11. Goedert JJ, Sarngadharan MG, Biggar RJ, et al. Determinants of retrovirus (HTLV-Ill) antibody and immunodeficiency conditions in homosexual men. Lancet 1984;2:711-16 12. Spira TJ, Des Jarlais DC, Marmor M, et al. Prevalence of antibody to lymphadenopathy-associated virus among drug-detoxification patients in New York. N Engl J Med 1984,311:467-8 13. Ramsey RB, Palmer EL, McDougal JS, et al. Antibody to lymphadenopathy-associated virus in hemophiliacs with and without AIDS. Lancet 1984,2:397-8 14. Tsoukas C, Gervais F, Shuster J, Gold P, O'Shaughnessy M, Robert-Guroff M. Association of HTLV- Ill antibodies and cellular immune status of hemophiliacs. N Engl J Med 1984;311:1514-15 15. Harris CA, Cabradilla C, Klein RS, et al. Antibodies to a core protein (p25) of lymphadenopathy as- sociated virus (LAV) and immunodeficiency in heterosexual partners of AIDS patients. Presentation at 24th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, D.C, 1984. 16. Anonymous. Needlestick transmission of HTLV-II from a patient infected in Africa. Lancet 1984; 2:1376-7. 17. Salahuddin SZ, Groopman JE, Markham PD, et al. HTLV-IIl in symptom-free seronegative persons. Lancet 1984; 2:1418-20. 18. Groopman JE. Unpublished data. 19. Groopman JE, Salahuddin SZ, Sarngadharan MG, et al. HTLV-Ill in saliva of people with AIDS- related complex and healthy homosexual men at risk for AIDS. Science 1984, 226:447-9. 20. Zagury D, Bernard J, Leibowitch J, et al. HTLV-II in cells cultured from semen of two patients with AIDS. Science 1984,;226:449-51. 21. Feorino PM, Jaffe HW, Palmer E, et al. Transfusion-associated acquired immunodeficiency syn- drome: evidence for persistent infection in blood donors. Submitted for publication. 22. Darrow WW, Jaffe HW, Braff E, et al. Acquired immunodeficiency syndrome (AIDS) in a cohort of homosexual men. Presentation at 24th Interscience Conference on Antimicrobial Agents and Che- motherapy. Washington, D.C., 1984. 23. Tsang VCW, Peralta JM, Simons AR. Enzyme-linked immunoelectrotransfer blot techniques (EITB) for studying the specificities of antigens and antibodies separated by gel electrophoresis. Methods Enzymol 1983;92:377-91. 1985 May 24 ,34:294 Testing Donors of Organs, Tissues, and Semen for Antibody to Human T-Lymphotropic Virus Type lll/Lymphadenopathy-Associated Virus The U.S. Public Health Service has recommended that all donated blood and plasma be tested for antibody to human T-lymphotropic virus type lll/lymphadenopathy-associated virus (HTLV-III/LAV), the virus that causes acquired immunodeficiency syndrome (AIDS) (7). It is additionally recommended that blood or serum from donors of organs, tissues, or semen in- tended for human use be similarly tested and that the test result be used to evaluate the ap- propriate use of such materials from these donors. Although AIDS has not been reported to have been associated with such use, semen and other body fluids, including blood, may harbor the virus. Thus, organs, tissues, and semen obtained from HTLV-III/LAV antibody-positive per- sons must be considered as potentially infectious. Persons in groups having an increased risk for AIDS should not donate organs, tissues, or semen, regardless of the result of the antibody test; this is the same policy currently followed for blood donations. It is recognized that the cir- cumstances of organ procurement and the logistics of transplantation may in some instances not permit the use of an HTLV-III/LAV test. However, when feasible such testing is prudent. Reported by U.S. Food and Drug Administration, Alcohol, Drug Abuse, and Mental Health Administration; National Institutes of Health, Health Resources and Svcs Administration, CDC. Reference 1. CDC. Provisional Public Health Service inter-agency recommendations for screening donated blood and plasma for antibody to the virus causing acquired immunodeficiency syndrome. MMWR 1985;34:1-5. 1985 Sept 6,34:547-48 Update: Revised Public Health Service Definition of Persons Who Should Refrain from Donating Blood and Plasma — United States Since March 1985, blood- and plasma-collection centers in the United States have used a two-phase screening procedure to decrease transmission of human T-lymphotropic virus type lll (HTLV-II) through transfusion of blood or blood products. First, potential donors are in- formed that if they have a risk factor for AIDS they should not donate (7); second, the blood or plasma of persons accepted as donors is screened for antibody to HTLV-II (2,3). The low frequency of enzyme immunoassay (EIA)-positive tests among blood donors (3,4) shows that the deferral criteria have been effective. Interviews with the small number of blood donors P-47 found infected with HTLV-II, however, have shown that most have a risk factor for HTLV-II in- fection; homosexual contact was the most common risk factor identified (5). To further reduce the risk of HTLV-II infection from blood and plasma, the U.S. Food and Drug Adminis- tration (FDA) has reworded the donor-deferral recommendations to state that any man who has had sex with another man since 1977 should not donate blood or plasma. This applies even to men who may have had only a single contact and who do not consider themselves homosexual or bisexual. Reported by Center for Drugs and Biologics, US Food and Drug Administration; AIDS Br, Div of Viral Dis- eases, Center for Infectious Diseases, CDC. Editorial Note: Recommendations to decrease transmission of HTLV-II through transfusion of blood or blood products were disseminated in March 1983 (7) and were rapidly adopted by blood and plasma centers throughout the United States. These recommendations centered on informing all blood or plasma donors that people with a risk factor for AIDS should not donate and asked for voluntary compliance. In March 1985, the second phase of screening blood and plasma was instituted with licensure of test kits to detect antibody to HTLV-II (2,3). The test kits are both highly sensitive and specific (4), but donors with a risk factor for HTLV-Ill infec- tion continue to be asked not to donate blood, since the two-phase screening procedure pro- vides additional safety. This revised wording of the deferral recommendations is intended to inform persons who may have been infected with HTLV-II through occasional or intermittent homosexual activity that they should not donate blood or plasma, even if they do not believe they are at risk of having been infected through their contacts. References 1. CDC. Prevention of acquired immune deficiency syndrome (AIDS): report of inter-agency recommen- dations. MMWR 1983;32:101-3. 2. CDC. Provisional Public Health Service inter-agency recommendations for screening donated blood and plasma for antibody to the virus causing acquired immunodeficiency syndrome. MMWR 1985;34:1-5. 3. CDC. Results of human T-lymphotropic virus type lll test kits reported from blood collection centers — United States, April 22,-May 19, 1985. MMWR 1985,34:375-6. 4. CDC. Update: Public Health Service workshop on human T-lymphotropic virus type lll antibody testing — United States. MMWR 1985,34:477-8. 5. Schorr JB, Berkowitz A, Cumming PD, Katz AJ, Sandler SG. Prevalence of HTLV-II antibody in Ameri- can blood donors. [Letter] N Engl J Med 1985;313:384-5. P-48 VI. VACCINES 1984 Dec 14,33:685—-87 Hepatitis B Vaccine: Evidence Confirming Lack of AIDS Transmission Recent studies have provided important additional assurances concerning the safety of hepatitis B (HB) vaccine. The vaccine currently licensed in the United States is produced from pooled plasma of hepatitis B surface antigen-positive individuals, some of whom are also in high-risk groups for acquired immunodeficiency syndrome (AIDS) Concern has been ex- pressed that the etiologic agent of AIDS might be present in the vaccine and survive the inactivation steps used in the manufacturing procedure. The concerns persisted, despite the fact that these steps were reportedly able to inactivate representative members of all known virus groups. The recent identification of a retrovirus as the etiologic agent of AIDS has allow- ed workers to (1) directly test the inactivation of the AIDS virus by the inactivation steps used in the vaccine manufacturing procedure; (2) look for the AIDS virus’ nucleic acid sequences in the vaccine; and (3) look for serologic markers of infection from the AIDS virus in vaccine recipients. Concurrently, monitoring of AIDS patients and high-risk groups has continued in order to look for any epidemiologic evidence of an association between HB vaccine and AIDS. The effect of the HB vaccine inactivation process on the AIDS virus and two other human retroviruses (HTLV-l and HTLV-II) was studied. Three separate inactivation steps are used in the manufacture of the U.S .-licensed HB vaccine: (1) 1 ug/ml pepsin, pH 2, 37 C (38.6 F), 18 hours; (2) 8 molar urea, 37 C (98.6 F), 4 hours; and (3) 0.01% formaldehyde, 37 C (98.6 F). 72 hours. In separate studies conducted between CDC and the vaccine manufacturer Merck, Sharp & Dohme (MSD), and between State University of New York (SUNY) Upstate Medical Center and MSD, cell culture supernatant fluid containing the AIDS virus and cultured cells containing HTLV-l, HTLV-II, and the AIDS virus were transported to MSD and individually ex- posed to the three inactivation steps. The materials were then returned to CDC and SUNY for detection of residual viral infectivity. Virus infectivity was assayed by adding the treated mate- rial to cultured lymphocytes and periodically monitoring these for signs of viral replication (reverse transcriptase activity and virus antigen expression) (7) and in the case of HTLV-l and HTLV-II, transformation (2,3). No residual virus was detected in material treated with formalin or urea, while material treated with pepsin at pH 2 did have residual virus present. Heat, an inactivation step used in vaccines manufactured outside the United States, has also been shown to inactivate the AIDS virus (4) The second approach, which attempted to detect AIDS virus-related nucleic acid sequenc- es using dot blot hybridization analysis of the vaccine with an AIDS virus deoxyribonucleic acid (DNA) probe, was done at MSD using as a positive control infected cellular (ribonucleic acid) RNA preparations provided by CDC. The vaccine contained no detectable AIDS virus-related sequences at a sensitivity of less than one picogram of DNA per 20-ug dose of vaccine. The third approach attempted to detect seroconversion to AIDS virus antibodies in paired sera of HB vaccine recipients. Paired sera were examined at CDC using a highly sensitive and specific ELISA assay for the AIDS virus. No seroconversions were detected in 19 individuals who had received vaccine manufactured from plasma pools that contained plasma of homo- sexual men. Previous workers have reported that sera of HB vaccine recipients did not show helper-T/supressor-T ratio inversion, a finding common in AIDS patients (5). Epidemiologic approaches to detect an association between HB vaccine and AIDS have included analysis of data on AIDS cases reported to CDC concerning their receipt of HB vac- cine and monitoring rates of AIDS in groups of homosexually active men who did or did not receive HB vaccine in the vaccine trials conducted by CDC in Denver, Colorado, and San Fran- cisco, California. To date, 68 AIDS cases have been reported among approximately 700,000 U.S. HB vaccine recipients; 65 have occurred among persons with known AIDS risk factors, while risk factors for the remaining three are under investigation. In addition, the rate of AIDS for HB vaccine recipients in CDC vaccine trials among homosexually active men in Denver and San Francisco does not differ from that for men screened for possible participation in the trials but who received no HB vaccine because they were found immune to HB. Reported by B Poiesz, MD, R Tomar, MD, B Lehr, J Moore, PhD, State University of New York Upstate Medical Center, Syracuse Veterans Administration Medical Center, Syracuse, New York, Merck, Sharp & Dohme Research Laboratories, West Point, Pennsylvania, AIDS Br, Hepatitis Br, Div of Viral Diseases, Center for Infectious Diseases, CDC P-50 Editorial Note: The Immunization Practices Advisory Committee (ACIP) (6) has recom- mended preexposure HB vaccination for susceptible members of the following groups in the United States: health-care workers (medical, dental, laboratory, and support groups) judged to have significant exposure to blood or blood products; clients and selected staff of institu- tions for the mentally retarded; hemodialysis patients; homosexually active males; users of illicit, injectable drugs; recipients of certain blood products (patients with clotting factor disor- ders); and household and sexual contacts of HB virus (HBV) carriers. In addition, vaccine may be warranted for classroom contacts of deinstitutionalized mentally retarded HBV carriers; special high-risk populations (Alaskan Eskimos and immigrants and refugees from areas with highly endemic disease); inmates of long-term correctional facilities; and some U.S. citizens living or traveling abroad (7). The ACIP has also recommended screening all pregnant women belonging to high-risk groups for HB and treating their newborn infants with hepatitis B immune globulin and HB vaccine (8). HB vaccine acceptance in the United States has been seriously hindered by the fear of possible AIDS transmission from the vaccine. The recent identification of AIDS’ etiologic agent has made possible direct laboratory measurement of virus inactivation, nucleic acid presence, and serologic evidence of infection. These studies were unable to detect the AIDS virus’ viral protein or nucleic acid in the purified vaccine product and clearly indicate that if virus were present, it would be killed by the manufacturing procedures. In addition, epidemio- logic monitoring of AIDS cases and high-risk groups confirms the lack of AIDS transmission by HB vaccine. This information should remove a major impediment to vaccine use. References 1. Feorino PM, Kalyanaraman VS, Haverkos HW, et al. Lymphadenopathy associated virus infection of a blood donor-recipient pair with acquired immunodeficiency syndrome. Science 1984,225:69-72. 2. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lympho- ma. Medical Sci 1980;77:7415-9 3 Kalyanaraman VS, Sarngadharan MG, Robert-Guroff RM, et al. A new subtype of human T-cell leuke- mia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science 1982;218.571-3. 4 CDC. Update: acquired immunodeficiency syndrome (AIDS) in persons with hemophilia. MMWR 1984;33:589-91 5. Jacobson IM, Dienstag JL, Zachoval R, Hanrahan BA, Watkins E, Rubin RH. Lack of effect of hepatitis B vaccine on T-cell phenotypes. N Engl J Med 1984,311 1030-2 6. ACIP. Inactivated hepatitis B virus vaccine. MMWR 1982,31:317-22, 327-8 7. CDC. Adult immunization: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1984,33 1S-68S. 8 ACIP. Post-exposure prophylaxis of hepatitis B. MMWR 1984,33.285-90 1986 April 11;35:231-33 Safety of Therapeutic Immune Globulin Preparations with Respect to Transmission of Human T-Lymphotropic Virus Type lll/Lymphadenopathy-Associated Virus Infection Immune globulins produced by plasma fractionation methods approved for use in the United States have not been implicated in the transmission of infectious agents. Nevertheless, because immune globulins manufactured before 1985 were derived from plasma of human donors who were not screened for antibody to human T-lymphotropic virus type lll/ lymphadenopathy-associated virus (HTLV-III/LAV), CDC and the U.S. Food and Drug Adminis- tration (FDA) have received inquiries concerning the safety of immune globulin (IG), hepatitis B immune globulin (HBIG), and intravenous immune globulin (IVIG). Current epidemiologic and laboratory evidence shows that these preparations carry no discernable risk of transmitting HTLV-III/LAV infection and that current indications for their clinical use should not be changed based on such concerns. BACKGROUND The IG, HBIG, IVIG, and other special immune globulins used in the United States are pro- duced by several manufacturers using the Cohn-Oncley fractionation process (7,2). This pro- cess involves a series of precipitation steps performed in the cold with addition of varying concentrations of ethanol. Production lots of IG and IVIG are made from plasma pools from at least 1,000 donors; HBIG and other specific immune globulins (e.g., varicella-zoster IG) may be prepared from plasma pools from fewer donors. Before 1985, donors were screened only for hepatitis B surface antigen but not by other tests for specific diagnosis of viral infections. Since April 1985, all donor units also have been screened for antibodies to HTLV-III/LAV, and all repeatedly reactive units have been discarded. Tests conducted at FDA and CDC have shown that as many as two-thirds of HBIG lots, as P-51 well as some lots of IG and IVIG, produced between 1982 and 1985 may have been positive for HTLV-III/LAV antibody. The question of safety arises out of concern that some immune globulins currently available were prepared from plasma pools that included units from donors who may have had HTLV-III/LAV viremia. EPIDEMIOLOGIC STUDIES Several studies have shown that recipients of HBIG and IG, including recipients of lots known to be positive for antibody to HTLV-III/LAV, did not seroconvert to antibody to HTLV-III/ LAV-positivity and have not developed signs and symptoms of acquired immunodeficiency syndrome (AIDS) or other illnesses suggesting HTLV-III/LAV infection. Since August 1983, CDC has enrolled 938 individuals who have had parenteral or mucous-membrane exposures to blood or body fluids of AIDS patients in a prospective sur- veillance study. To date, 451 entrants have been followed and tested for HTLV-III/LAV anti- body. Of these, 183 persons received IG and/or HBIG as prophylaxis against hepatitis 3 infec- tion; 100 (55%) received only IG; 65 (36%) received only HBIG; and 18 (10%) received both. One of the 183 HBIG recipients is now positive for HTLV-III/LAV antibody, but no preexposure serum was available for this individual, and seropositivity may have predated the needlestick exposure and |G prophylaxis. Further, heterosexual transmission of HTLV-III/LAV infection in this individual cannot be ruled out. No documented seroconversions have occurred in any of the 183 health-care workers who received IG or HBIG. Studies have been reported of 16 subjects who received HBIG that was strongly positive for HTLV-III/LAV antibody (3). Each patient had been given one to five ampules. A total of 31 doses were administered to 16 individuals. Low levels of passively acquired HTLV-III/LAV an- tibody were detected shortly after injection, but reactivity did not persist. Six months after the last HBIG injection, none of the 16 individuals had antibody to HTLV-III/LAV. In a study of prophylaxis against cytomegalovirus (CMV) infections among kidney- transplant patients, 16 patients received CMV-specific IVIG preparations subsequently found to contain HTLV-III/LAV antibody. After 10 months or longer of follow-up, none of the 16 recipients developed antibody or other evidence of HTLV-IlI/LAV infection. In studies of a group of IVIG recipients, most of whom had idiopathic thrombocytopenia, none of 134 patients developed antibodies or other evidence of HTLV-III/LAV infection. Information regarding past therapy with immune globulins is available from 10,227 of 17,115 AIDS patients reported to CDC. Three hundred fifty-eight (4%) reported receipt of an IG preparation. All but seven of these patients also were members of groups known to be at high risk for developing AIDS. The percentage of patients with no recognized risk factors for AIDS was not significantly different among those who received immune globulins (7/358 [2%]) than among those who did not (358/9,869 [4%]). LABORATORY STUDIES Scientists at FDA recently evaluated the basic fractionation processes (7,2) used for pro- duction of immune globulins to determine effectiveness of those procedures in eliminating HTLV-III/LAV infectivity (4). Six sequential steps in a typical process were evaluated. The study was designed so that efficiency of eliminating HTLV-III/LAV at each step was measured. The degree to which HTLV-III/LAV was reduced by partitioning or inactivation at individual steps ranged from 10°! to more than 10* of in vitro infectious units (IVIU)/ml. The effective- ness of virus removal in the entire process by partitioning and inactivation was calculated to be greater than 1 x 10% IVIU/ml. Concentrations of infectious HTLV-III/LAV in plasma of infected persons have been es- timated to be less than 100 IVIU/ml. Further, FDA scientists have shown that the geometric mean infectivity titer of plasma from 43 HTLV-III/LAV infected persons was 0.02 IVIU/mI (4). Thus, the margin of safety based on the removal of infectivity by the fractionation process is extremely high. Scientists at CDC and FDA also cultured 38 lots of HBIG, IVIG, and IG, most of which con- tained HTLV-III/LAV antibody. HTLV-III/LAV was not recovered from any lot tested. Reported by J Bossell, MD, Cornell University, New York City; Central Laboratories Swiss Red Cross Blood Transfusion Svc, Berne, Switzerland, Immuno A.G., Vienna, Austria, KabiVitrum AB, Stockholm, Sweden; Massachusetts Public Health Biologics Laboratories, Boston, Massachusetts, Miles Laborato- ries, Inc., Berkeley, Travenol Laboratories, Inc., Glendale, California; Center for Drugs and Biologics, U.S. Food and Drug Administration, Center for Infectious Diseases, COC. Editorial Note: The laboratory and epidemiologic studies referred to have shown that con- cern about HTLV-III/LAV infection associated with the use of immune globulins available in the United States is not warranted. Strategies for using immune globulins recommended by the Immunization Practices Advisory Committee should be followed (5). Recently, concern has been expressed that patients who received IG prepared from plasma of donors not screened for HTLV-III/LAV antibody may have a passively acquired P-52 false-positive reaction for antibody (6). Passively acquired HTLV-II LAV antibody from HBIG known to contain high levels of antibody has heen reported (3). Based on the estimated half- life of globulins in plasma, it can be calculate: that passively acquired antibodies might be detected in sera of recipients for as long as 6 months after administration of immune globu- lins. It is important to recognize this possibility when attempting to determine the significance of HTLV-IIIVLAV antibody in a person who has recently received immune globulins, especially HBIG. References 1. Cohn EJ, Strong LE, Hughes WI Jr, et al. Preparation and properties of serum and plasma proteins IV. A system for the separation into fractions of protein and lipoprotein components of biological tissues and fluids J Am Chem Soc 1946,68:459-75 2. Oncley JL, Melin M, Richert DA, Cameron JW, Gross PM Jr. The separation of the antibodies isoag- glutinins, prothrombin, plasmonogen and beta-lipoprotein into subfractions of human plasma J Am Chem Soc 1949;71:541-50 3. Tedder RS, Uttley A, Cheingsong-Popov R. Safety of immunoglobulin preparation containing anti- HTLV-II (Letter). Lancet 1985,1. 815. 4. Wells MA, Wittek A, Marcus-Sekura C, et al. Chemical and physical inactivation of human T lym- photropic virus, Type Ill (HTLV-II). Transfusion 1986,26:110-30 5. ACIP. Recommendations for protection against viral hepatitis MMWR 1985;34:313-24, 329-35. 6. Steele DR. HTLV-Ill antibodies in human immune y-globulin [Letter]. JAMA 1986,255:609 1986 September 26, 35: 595-598, 603-06 Immunization of Children Infected with Human T-Lymphotropic Virus Type IlI/ Lymphadenopathy-Associated Virus INTRODUCTION This document is intended to summarize available information and to assist health-care providers in developing policies for the immunization of children infected with human T- lymphotropic virus type lll/lymphadenopathy-associated virus (HTLV-III/LAV),* the virus that causes acquired immunodeficiency syndrome (AIDS). These policies may vary depending upon the prevalence of HTLV-III/LAV infection and the incidence of vaccine-preventable dis- eases in the community, individual assessment of a child's health status, and the risks and benefits of immunization in a particular situation. This discussion considers the risks and benefits of immunization for children residing in the United States based on the risks of vaccine-preventable diseases and the prevalence of HTLV-III/LAV infection and is intended for use by health-care providers in the United States. The recommendations may not pertain to other countries with different risks of vaccine-preventable diseases and prevalence of HTLV-III/LAV infection among children. Since these recommendations are based upon infor- mation and knowledge available at this time, periodic reassessment and revision will be re- quired as more data concerning risk and benefits associated with immunization of HTLV-III/ LAV-infected children become known and as the prevalences of specific vaccine-preventable diseases and HTLV-lll infection change. HTLV-III/LAV INFECTION AMONG CHILDREN In the period June 1, 1981-September 2, 1986, physicians and health departments in the United States reported 24,430 cases of AIDS to CDC (7). Three hundred forty-five (1%) of the case-patients were children under 13 years of age who met the AIDS case definition; 75% of these pediatric cases were reported from New York, Florida, New Jersey, and California. Children with less severe manifestations of HTLV-III/LAV infection (AIDS-related complex, or ARC) or with asymptomatic infections are not now reported to CDC, and no seroprevalence studies have been conducted among children. Thus, the number of less severely affected children and the number of infected but presently asymptomatic children are uncertain. In one recently published case series, 14 (48%) of 29 symptomatic HTLV-III/LAV-infected children met the CDC criteria for AIDS (2). Fifty percent of children reported to CDC were diagnosed as having AIDS during the first year of life; 82%, by 3 years of age (7). Sixty-five percent of pediatric AIDS cases reported to CDC were fatal (3). Short-term fatality rates are lower for children with less severe disease (ARC) who have not developed opportunistic infections; however, the ultimate prognosis of these children and of asymptomatic infected children is unknown. ‘The AIDS virus has been variously termed human T-lymphotropic virus type Ill (HTLV-III/LAV), lymphadenopathy-associated virus (LAV), AIDS-associated retrovirus (ARV), or human immunodeficien- cy virus (HIV). The designation “human immunodeficiency virus” (HIV) has been accepted by a subcom- mittee of the International Committee for the Taxonomy of Viruses as the appropriate name for the retro- virus that has been implicated as the causative agent of AIDS (Science 1986,232 697) P-53 MECHANISMS OF TRANSMISSION OF HTLV-1II/LAV AMONG CHILDREN Two risk factors are predominately associated with HTLV-III/LAV infection in children: a) being born to a mother who has HTLV-IlI/LAV infection, and b) receiving blood or clotting factors containing HTLV-III/LAV. Most case-patients (79%) are children whose mothers probably are infected with the virus. The major risk factors for infection of these women are intravenous (IV) drug abuse and sexual contact with men at risk of HTLV-III/LAV infection (pri- marily through drug abuse or bisexual contacts); women of Haitian or central African origin are also at a higher risk of acquiring HTLV-III/LAV infection, and a small percentage of infected women have a history of being transfused with blood (4). Approximately 15% of pediatric AIDS case-patients have received transfusions of blood or blood products, and 4% have hemophilia and have been treated with clotting-factor concentrates. Information about risk factors is incomplete for 3% of children with AIDS. Currently available data indicate that most pediatric HTLV-III/LAV infections are acquired from infected women during pregnancy, during labor and delivery, or perhaps shortly after birth. The risk of perinatal transmission from an infected mother to her infant is not known, al- though prospective studies indicate the rate of transmission has ranged from 0% (0/3) to 65% (13/20) (5-7). Seropositive women who had previously delivered an infected child had the highest of these transmission rates (65%) in subsequent pregnancies (5). In a retrospective study evaluating nine children whose mothers were later diagnosed as having AIDS, two (22%) children had antibody to HTLV-III/LAV (8). Additional prospective studies are needed to define more precisely the rate of perinatal transmission of HTLV-lII/LAV. PREVALENCE OF HTLV-III/LAV INFECTION AMONG WOMEN OF CHILD-BEARING AGE The prevalence of HTLV-III/LAV infection among women of child-bearing age varies depending on the patient group and geographic area (4). Reported confirmed seropreva- lences are less than 0.01% among female blood donors in Atlanta and 0.06% among female U.S. military recruit applicants (4,9). In contrast, the reported prevalence of HTLV-III/LAV anti- body among IV drug abusers has ranged from 2% to 59%, with the highest prevalence in New York City and northern New Jersey. Female sex partners of IV drug-abusing men with AIDS or with ARC had a reported seroprevalence of 40%-71%, whereas 10% of female partners of asymptomatic infected hemophiliacs were reported to be seropositive (4). Seroprevalence among prostitutes has varied greatly (5%-40%) depending on the geographic area and has been largely attributed to a coincidental history of IV drug abuse (4). Seroprevalence has been reported to be as high as 5% among persons born in countries in which heterosexual transmission of HTLV-III/LAV is thought to play a major role (e.g., Haiti, central African coun- tries) (7,710,717). IMMUNOLOGIC ABNORMALITIES ASSOCIATED WITH HTLV-III/LAV INFECTION Children with symptomatic HTLV-III/LAV infection (AIDS or ARC) have immunologic abnor- malities similar to those of adult AIDS patients, including hypergammaglobulinemia, decreased T4 lymphocytes, reversed helper/suppressor T-cell ratios, poor T-lymphocyte responses to mitogen stimulation, and altered humoral immunity. Lymphopenia (cell counts less than 1,500 cells/mm?3) is uncommon. Antibody responses of children with AIDS or ARC to diphtheria and tetanus toxoid boosters and to pneumococcal vaccine were absent or lower than those of age- matched controls, which is consistent with defective humoral immunity (72,73). Some HTLV-II/LAV-infected children responded adequately to immunization; 60% of AIDS and ARC patients given measles-mumps-rubella vaccine (MMR) prior to diagnosis had protec- tive levels of measles antibodies 5-66 months after immunization (74). Asymptomatic HTLV-III/LAV-infected adults as a group generally have less severe abnor- malities of immunologic function than adults with AIDS or ARC, and some may have normal immunologic function, although individual asymptomatic adults may have severe abnormali- ties (75). Immunologic function of asymptomatic HTLV-lII/LAV-infected children has not yet been adequately studied but presumably would be more intact than that of symptomatic HTLV-III/LAV-infected children. In a small prospective study, all 29 children with symptomatic HTLV-III/LAV infection had immunologic abnormalities within 5-13 months of being found in- fected, compared with only two of seven (29%) children reported to have asymptomatic HTLV-III/LAV infection (2). CONCERNS ABOUT IMMUNIZATION OF HTLV-1II/LAV-INFECTED CHILDREN The immunologic abnormalities associated with symptomatic HTLV-III/LAV infection have raised concerns about the immunization of infected children. Replication of live, attenuated vaccine viruses may be enhanced in persons with immunodeficiency diseases and theoreticai- ly may produce serious adverse events following immunization of symptomatic HTLV-III/ LAV-infected (AIDS and ARC) patients (76). Concerns have been expressed on theoretical grounds that antigenic stimulation by immunization with inactivated vaccines might lead to a P-54 deterioration of clinical status of HTLV-III/LAV-infected children, but this effect has not been documented (77). Since symptomatic HTLV-III/LAV-infected patients have abnormal primary and secondary antibody responses, the efficacy of immunization may be decreased (78). The efficacy of immunization for asymptomatic HTLV-III/LAV-infected children is unknown, but presumably would be higher than for symptomatic HTLV-III/LAV-infected children. Because most HTLV-IlII/LAV-infected children become infected perinatally, it is to be ex- pected that their mothers are infected with HTLV-III/LAV. Other family members may also be infected with HTLV-III/LAV and may have abnormal immunologic function.’ Prospective eval- uation of 16 asymptomatic HTLV-lII/LAV-infected mothers of children diagnosed as having AIDS or ARC showed that 12 (75%) mothers developed AIDS or ARC during a 30-month follow-up period (6). Regardless of the immune status of the recipient, poliovaccine virus is often excreted by children vaccinated with oral poliovaccine (OPV) and may be transmitted to close contacts (79). Immune-deficient individuals (either recipients or contacts) have a higher risk of developing vaccine-associated poliomyelitis than normal individuals. There is no risk of transmitting the viruses contained in measles, mumps, rubella (MMR) vaccine to family mem- bers (20-22). While the risks of vaccination are not known with certainty, potential risks may exist if HTLV-II/LAV-infected children are not vaccinated. If local outbreaks of measles occur in geographic areas in which there is both a cluster of unvaccinated children and a high preva- lence of HTLV-III/LAV infection, the risk of measles for unvaccinated, HTLV-III/LAV-infected children may be high. Measles infection among patients with immune deficiency may be severe, protracted, and fatal (23). EXPERIENCES WITH IMMUNIZATION OF HTLV-III/LAV-INFECTED PERSONS Some children infected perinatally with HTLV-III/LAV have received routine immunization with OPV and MMR before their illnesses were recognized. Out-patient medical records from New York City and Miami for 213 children with symptomatic HTLV-III/LAV infection (AIDS and ARC), presumably acquired during the perinatal period, were reviewed to determine im- munization history and possible vaccine-associated adverse events (24,25). One hundred seventy-one children (80%) had received at least one dose of OPV and diphtheria and tetanus toxoids and pertussis vaccine (DTP), 95 (45%) had completed primary immunization with OPV and DTP (three doses and four doses, respectively), and 63 (30%) had received MMR or measles vaccine. Thirty-eight (39%) of 98 children who had available records of dates of im- munization and onset of symptoms consistent with HTLV-III/LAV infection had received at least one live-virus vaccine after symptom onset. No serious or unusual adverse events were noted in the medical records of these children following immunization. Only one adverse event following immunization of an HTLV-III/LAV-infected person has been documented. A 19-year-old asymptomatic army recruit received multiple immunizations during basic training, including primary immunization with smallpox vaccine (26). Two and one-half weeks later, he developed cryptococcal meningitis and was diagnosed as having AIDS. One and one-half weeks later, while being treated for meningitis, he developed lesions of disseminated vaccinia. He was treated with vaccinia immune globulin and recovered from vaccinia, but has since died of AIDS. CDC has not received any reports of vaccine-associated poliomyelitis among HTLV-IIl/ LAV-infected vaccine recipients or their contacts or among other persons known to be infect- ed with HTLV-III/LAV. There have been no reports of serious adverse events following MMR administration from areas in which pediatric AIDS cases are occurring. IMMUNIZING CHILDREN WHO MAY BE INFECTED WITH HTLV-III/LAV: SPECIAL CONSIDERATIONS Children born to women who are at risk of HTLV-III/LAV infection or who are known to be infected with HTLV-III/LAV should be evaluated for infection with the virus—including being tested for antibody (4,27). For asymptomatic children presenting for immunization, this eval- uation and testing is not necessary to make decisions about immunizations. Children infected with HTLV-III/LAV are best cared for by pediatricians knowledgeable in the management of patients with this infection. Since little information is currently available on the safety and ef- ficacy of immunizing children who may be infected with HTLV-III/LAV, special studies of these children need to be conducted. tSuch family members may have been infected by sexual contact with an HTLV-III/LAV-infected person, by parenteral exposure to infected blood (e.g., by sharing needles), or as hemophiliacs who received clot- ting factors, or by perinatal transmission. P-55 RECOMMENDATIONS Children with symptomatic HTLV-III/LAV infection A. Live-virus and live-bacterial vaccines (e.g., MMR, OPV, BCG) should not be given to chil- dren and young adults who are immunosuppressed in association with AIDS or other clini- cal manifestations of HTLV-III/LAV infection. For routine immunizations, these persons should receive inactivated poliovaccine (IPV) and should be excused for medical reasons from regulations requiring measles, rubella, and/or mumps immunization. B. Concerns have been raised that stimulation of the immune system by immunization with inactivated vaccines in these individuals might cause deterioration in immunologic function. However, such effects have not been noted thus far among children with AIDS or among other immunosuppressed individuals after immunization with inactivated vaccines. The potential benefits of immunization of these children outweigh the concerns of theoretical adverse events. Immunization with DTP, IPV, and Haemophilus influenzae type b vaccines is recommended in accordance with the ACIP recommendations, although immunization may be less effective than it would be for immunocompetent children (28-30). C. As with other conditions that produce chronic immunosuppression, the Committee recom- mends annual immunization with inactivated influenza vaccine for children over 6 months of age and one-time administration of pneumococcal vaccine for children over 2 years of age (37-33). D. Children and young adults with AIDS or other clinical manifestations of HTLV-IlI/LAV infection — as other immunosuppressed patients —may be at increased risk of having serious complications of infectious diseases, such as measles and varicella. Following significant exposure to measles or varicella, these persons should receive passive immunization with immune globulin (IG) or varicella-zoster immune globulin (VZIG), respectively (20,34). Children with previously diagnosed asymptomatic HTLV-III/LAV infection A. A small number of children and young adults known to be infected with HTLV-III/LAV but without overt clinical manifestations of immunosuppression have received live-virus vac- cines without adverse consequences. Further experience needs to be monitored, but on the basis of data now available, the Committee believes that such persons should be vac- cinated with MMR in accordance with ACIP recommendations (20-22). Vaccinees should be followed for possible adverse reactions and for the occurrence of vaccine-preventable diseases since immunization may be less effective than for uninfected persons. B. Available data suggest that OPV can be administered without adverse consequences to HTLV-IIl/LAV-infected children who do not have overt clinical manifestations of immuno- suppression. However, because family members of such children may be immunocompro- mised due to AIDS or HTLV-III/LAV infection and therefore at increased risk of paralysis from contact with spread vaccine virus, it may be prudent to use IPV routinely to immunize asymptomatic children with previously diagnosed HTLV-III/LAV infection (28). C. Immunization with DTP and Haemophilus influenzae type b vaccines is recommended in accordance with ACIP recommendations (29,30). Children not known to be infected with HTLV-III/LAV Children and young adults not known to be infected with HTLV-III/LAV should be immu- nized in accordance with ACIP recommendations. Children residing in the household of a patient with AIDS Children whose household members are known to be immunocompromised due to AIDS or other HTLV-III/LAV infections should not receive OPV because vaccine viruses are excreted by the recipient of the vaccine and may be communicable to their immunosuppressed con- tacts. These children should receive IPV for routine iminunization (28). Because extensive ex- perience has shown that live, attenuated MMR vaccine viruses are not transmitted from vac- cinated individuals to others, MMR may be given to a child residing in the household of a pa- tient with AIDS (20-22). References 1. CDC. Unpublished data. 2. Pahwa S, Kaplan M, Fikrig S, et al. Spectrum of human T-cell lymphotropic virus type lll infection in children. JAMA 1986;255:2299-2305. 3. Rogers MF. AIDS in children: a review of the clinical, epidemiologic and public health aspects. Pedi- atr Infect Dis 1985,4:230-6. some physicians administer full replacement doses of intravenous IG on a 2-4 week schedule to chil- dren with AIDS and other clinical manifestations of HTLV-IlI/LAV infection. This therapy may provide some protection against such diseases as measles and varicella. P-56 10. 14. 15. 16. 12. 18. 25. 237. 28. 30. 31. 32. 34. CDC. Recommendations for assisting in the prevention of perinatal transmission of human T- lymphotropic virus type lll/lymphadenopathy-associated virus and acquired immunodeficiency syn- drome. MMWR 1985,34:721-32 Scott GB, Fischl MA, Klimas N, et al. Mothers of infants with the acquired immunodeficiency syn- drome: outcome of subsequent pregnancies. Atlanta, Georgia: International conference on acquired immunodeficiency syndrome, April 14-17, 1985 Scott GB, Fischl MA, Klimas N, et al. Mothers of infants with the acquired immunodeficiency syn- drome. Evidence for both symptomatic and asymptomatic carriers. JAMA 1985,253:363-6. Stewart GJ, Tyler JP, Cunningham AL, et al. Transmission of human T-cell lymphotropic virus type Il (HTLV-II) by artificial insemination by donor. Lancet 1985,2:581-5 Thomas PA, Lubin K, Enlow RW, et al. Comparison of HTLV-Ill serology, T-cell levels, and general health status of children whose mothers have AIDS with children of healthy inner city mothers in New York. Atlanta, Georgia: International conference on acquired immunodeficiency syndrome, April 14-17, 1985. CDC. Human T-lymphotropic virus type lll/lymphadenopathy-associated virus antibody prevalence in U.S. military recruit applicants. MMWR 1986,35:421-4. World Health Organization. Acquired immune deficiency syndrome (AIDS). Report on the situation in Europe as of 31 December 1984. Wkly Epidem Rec 1985,60:85-90. Castro KG, Fischl MA, Landesman SH, et al. Risk factors for AIDS among Haitians in the United States. Atlanta, Georgia: International conference on acquired immunodeficiency syndrome. April 14-17,1985. Bernstein LJ, Ochs HD, Wedgwood RJ, Rubenstein A. Defective humoral immunity in pediatric ac- quired immune deficiency syndrome. J Pediatr 1985,107:352-7. Borkowsky W, Krasinski K. Residual cell-mediated immunity to recall antigens in pediatric AIDS- related disease. Pediatr Res 1986,20:292A. Krasinski K, Borkowsky W, Krugman S. Antibody following measles immunization in children infect- ed with human T-cell lymphotropic virus-type lll/lymphadenopathy associated virus (HTLV-III/LAV). Paris, France: International conference on acquired immunodeficiency syndrome, June 23-25, 1986. Francis DP, Jaffe HW, Fultz PN, Getchell JP, McDougal JS, Feorino PM. The natural history of infec- tion with the lymphadenopathy-associated human T-lymphotropic virus type lll. Ann Intern Med 1986;103:719-22. ACIP. General recommendations on immunization. MMWR 1983,32:1-8, 13-17. Zagury D, Bernard J, Leonard R, et al. Long-term cultures of HTLV-lll-infected T cells: a model of cy- topathology of T-cell depletion in AIDS. Science 1986,231:850-3. Simberkoff MS, El Sadr W, Schiffman G, Rahal JJ, Jr. Streptococcus pneumoniae infections and bacteremia in patients with acquired immune deficiency syndrome, with report of a pneumococcal vaccine failure. Am Rev Respir Dis 1984,;130:1174-6. CDC. Paralytic poliomyelitis — United States, 1982 and 1983. MMWR 1984,33:635-8. ACIP. Measles prevention. MMWR 1982;31:217-24, 229-31. ACIP. Rubella prevention. MMWR 1984;33:301-10, 315-8. ACIP. Mumps vaccine. MMWR 1982:31:617-20, 625. Cherry JD. Measles. In Feigin, RD and Cherry, JD (eds): Textbook of Pediatric Infectious Diseases. Philadelphia, W.B. Saunders Company, 1981:1210-31. Mclaughlin M, Thomas P, Rubenstein A, et al. Use of live virus vaccines in children with HTLV-IIl/LAV infection: a retrospective survey. Paris, France: International conference on acquired immuno- deficiency syndrome, June 23-25, 1986. Gwendolyn Scott. Personal communication. R. Redfield. Personal communication. CDC. Additional recommendations to reduce sexual and drug abuse-related transmission of human T-lymphotropic virus type lll/lymphadenopathy-associated virus. MMWR 1986;35:152-5. ACIP. Poliomyelitis prevention. MMWR 1982,31:22-6,31-4. ACIP. Diphtheria, tetanus, and pertussis: guidelines for vaccine prophylaxis and other preventive measures. MMWR 1985,34:405-14, 419-26. ACIP. Polysaccharide vaccine for prevention of Haemophilus influenzae type b disease. MMWR 1985,34:201-5. ACIP. Update: pneumococcal polysaccharide vaccine usage — United States. MMWR 1984; 33:273-6, 281. ACIP. Prevention and control of influenza. MMWR 1986,35:317-26, 331. ACIP. Monovalent influenza A(H1N1) vaccine, 1986-1987. MMWR 1986;35:517-21. ACIP. Varicella-zoster immune globulin for the prevention of chickenpox. MMWR 1984:33:84-90, 95-100. P~57 Vil. MATERNAL AND CHILD HEALTH 1985 Aug 30;34:517-21 Education and Foster Care of Children Infected with Human T-Lymphotropic Virus Type lIl/ Lymphadenopathy-Associated Virus The information and recommendations contained in this document were developed and compiled by CDC in consultation with individuals appointed by their organizations to represent the Conference of State and Territorial Epidemiologists, the Association of State and Territo- rial Health Officers, the National Association of County Health Officers, the Division of Mater- nal and Child Health (Health Resources and Services Administration), the National Association for Elementary School Principals, the National Association of State School Nurse Consultants, the National Congress of Parents and Teachers, and the Children’s Aid Society. The consult- ants also included the mother of a child with acquired immunodeficiency syndrome (AIDS), a legal advisor to a state education department, and several pediatricians who are experts in the field of pediatric AIDS. This document is made available to assist state and local health and education departments in developing guidelines for their particular situations and locations. These recommendations apply to all children known to be infected with human T-lympho- tropic virus type lll/lymphadenopathy-associated virus (HTLV-III/LAV). This includes children with AIDS as defined for reporting purposes (Table 1); children who are diagnosed by their physicians as having an illness due to infection with HTLV-III/LAV but who do not meet the case definition; and children who are asymptomatic but have virologic or serologic evidence of infection with HTLV-III/LAV. These recommendations do not apply to siblings of infected children unless they are also infected. BACKGROUND The Scope of the Problem. As of August 20, 1985, 183 of the 12,599 reported cases of AIDS in the United States were among children under 18 years of age. This number is expect- ed to double in the next year. Children with AIDS have been reported from 23 states, the Dis- trict of Columbia, and Puerto Rico, with 75% residing in New York, California, Florida, and New Jersey. The 183 AIDS patients reported to CDC represent only the most severe form of HTLV- II/LAV infection, i.e., those children who develop opportunistic infections or malignancies (Table 1). As in adults with HTLV-III/LAV infection, many infected children may have milder ill- ness or may be asymptomatic. Legal Issues. Among the legal issues to be considered in forming guidelines for the educa- tion and foster care of HTLV-IlI/LAV-infected children are the civil rights aspects of public school attendance, the protections for handicapped children under 20 U.S.C. 1401 et seq. and 29 U.S.C. 794, the confidentiality of a student's school record under state laws and under 20 U.S.C. 1232g, and employee right-to-know statutes for public employees in some states. TABLE 1. Provisional case definition for acquired immunodeficiency syndrome (AIDS) surveillance of children For the limited purposes of epidemiologic surveillance, CDC defines a case of pediatric ac- quired immunodeficiency syndrome (AIDS) as a child who has had: 1. A reliably diagnosed disease at least moderately indicative of underlying cellular immuno- deficiency, and 2. No known cause of underlying cellular immunodeficiency or any other reduced resistance reported to be associated with that disease. The diseases accepted as sufficiently indicative of underlying cellular immunodeficiency are the same as those used in defining AIDS in adults. In the absence of these opportunistic diseases, a histologically confirmed diagnosis of chronic lymphoid interstitial pneumonitis will be consid- ered indicative of AIDS unless test(s) for HTLV-III/LAV are negative. Congenital infections, e.g. toxoplasmosis or herpes simplex virus infection in the first month after birth or cytomegalovirus infection in the first 6 months after birth must be exluded. Specific conditions that must be excluded in a child are: 1. Primary immunodeficiency diseases —severe combined immunodeficiency, DiGeorge syn- drome, Wiskott-Aldrich syndrome, ataxia-telangiectasia, graft versus host disease, neu- tropenia, neutrophil function abnormality, agammaglobulinemia, or hypogammaglobuline- mia with raised IgM. 2. Secondary immunodeficiency associated with immunosuppressive therapy, lymphoreticu- lar malignancy, or starvation. P-58 Confidentiality Issues. The diagnosis of AIDS or associated illnesses evokes much fear from others in contact with the patient and may evoke suspicion of life styles that may not be acceptable to some persons. Parents of HTLV-lII/LAV-infected children should be aware of the potential for social isolation should the child's condition become known to others in the care or educational setting. School, day-care, and social service personnel and others involved in educating and caring for these children should be sensitive to the need for confidentiality and the right to privacy in these cases. ASSESSMENT OF RISKS Risk Factors for Acquiring HTLV-III/LAV Infection and Transmission. In adults and ado- lescents, HLTV-HII/LAV is transmitted primarily through sexual contact (homosexual or hetero- sexual) and through parenteral exposure to infected blood or blood products. HTLV-lII/LAV has been isolated from blood, semen, saliva, and tears but transmission has not been docu- mented from saliva and tears. Adults at increased risk for acquiring HTLV-III/LAV include homosexual/bisexual men, intravenous drug abusers, persons transfused with contaminated blood or blood products, and sexual contacts of persons with HTLV-III/LAV infection or in groups at increased risk for infection. The majority of infected children acquire the virus from their infected mothers in the perinatal period (7-4). In utero or intrapartum transmission are likely, and one child reported from Australia apparently acquired the virus postnatally, possibly from ingestion of breast milk (5). Children may also become infected through transfusion of blood or blood products that contain the virus. Seventy percent of the pediatric cases reported to CDC occurred among children whose parent had AIDS or was a member of a group at increased risk of ac- quiring HTLV-III/LAV infection; 20% of the cases occurred among children who had received blood or blood products; and for 10%, investigations are incomplete. Risk of Transmission in the School, Day-Care or Foster-Care Setting. None of the identified cases of HTLV-III/LAV infection in the United States are known to have been trans- mitted in the school, day-care, or foster-care setting or through other casual person- to-person contact. Other than the sexual partners of HTLV-IlI/LAV-infected patients and in- fants born to infected mothers, none of the family members of the over 12,000 AIDS patients reported to CDC have been reported to have AIDS. Six studies of family members of patients with HTLV-III/LAV infection have failed to demonstrate HTLV-III/LAV transmission to adults who were not sexual contacts of the infected patients or to older children who were not likely at risk from perinatal transmission (6-717). Based on current evidence, casual person-to-person contact as would occur among schoolchildren appears to pose no risk. However, studies of the risk of transmission through contact between younger children and neurologically handicapped children who lack control of their body secretions are very limited. Based on experience with other communicable dis- eases, a theoretical potential for transmission would be greatest among these children. It should be emphasized that any theoretical transmission would most likely involve exposure of open skin lesions or mucous membranes to blood and possibly other body fluids of an in- fected person. Risks to the Child with HTLV-III/LAV Infection. HTLV-III/LAV infection may result in im- munodeficiency. Such children may have a greater risk of encountering infectious agents in a school or day-care setting than at home. Foster homes with multiple children may also in- crease the risk. In addition, younger children and neurologically handicapped children who may display behaviors such as mouthing of toys would be expected to be at greater risk for acquiring infections. Immunodepressed children are also at greater risk of suffering severe complications from such infections as chickenpox, cytomegalovirus, tuberculosis, herpes sim- plex, and measles. Assessment of the risk to the immunodepressed child is best made by the child's physician who is aware of the child's immune status. The risk of acquiring some infec- tions, such as chickenpox, may be reduced by prompt use of specific immune globulin follow- ing a known exposure. RECOMMENDATIONS 1. Decisions regarding the type of educational and care setting for HTLV-IlI/LAV-infected children should be based on the behavior, neurologic development, and physical con- dition of the child and the expected type of interaction with others in that setting. These decisions are best made using the team approach including the child's physi- cian, public health personnel, the child's parent or guardian, and personnel associated with the proposed care or educational setting. In each case, risks and benefits to both - the infected child and to others in the setting should be weighed. 2. For most infected school-aged children, the benefits of an unrestricted setting would outweigh the risks of their acquiring potentially harmful infections in the setting and P-59 10. 11, the apparent nonexistent risk of transmission of HTLV-III/LAV. These children should be allowed to attend school and after-school day-care and to be placed in a foster home in an unrestricted setting. For the infected preschool-aged child and for some neurologically handicapped chil- dren who lack control of their body secretions or who display behavior, such as biting, and those children who have uncoverable, oozing lesions, a more restricted environ- ment is advisable until more is known about transmission in these settings. Children in- fected with HTLV-III/LAV should be cared for and educated in settings that minimize exposure of other children to blood or body fluids. Care involving exposure to the infected child's body fluids and excrement, such as feeding and diaper changing, should be performed by persons who are aware of the child's HTLV-III/LAV infection and the modes of possible transmission. In any setting involving an HTLV-III/LAV-infected person, good handwashing after exposure to blood and body fluids and before caring for another child should be observed, and gloves should be worn if open lesions are present on the caretaker’s hands. Any open lesions on the infected person should also be covered. Because other infections in addition to HTLV-III/LAV can be present in blood or body fluids, all schools and day-care facilities, regardless of whether children with HTLV-III/ LAV infection are attending, should adopt routine procedures for handling blood or body fluids. Soiled surfaces should be promptly cleaned with disinfectants, such as household bleach (diluted 1 part bleach to 10 parts water). Disposable towels or tissues should be used whenever possible, and mops should be rinsed in the disinfect- ant. Those who are cleaning should avoid exposure of open skin lesions or mucous membranes to the blood or body fluids. The hygienic practices of children with HTLV-III/LAV infection may improve as the child matures. Alternatively, the hygienic practices may deteriorate if the child's con- dition worsens. Evaluation to assess the need for a restricted environment should be performed regularly. . Physicians caring for children born to mothers with AIDS or at increased risk of ac- quiring HTLV-III/LAV infection should consider testing the children for evidence of HTLV-III/LAV infection for medical reasons. For example, vaccination of infected children with live virus vaccines, such as the measles-mumps-rubella vaccine (MMR), may be hazardous. These children also need to be followed closely for problems with growth and development and given prompt and aggressive therapy for infections and exposure to potentially lethal infections, such as varicella. In the event that an antiviral agent or other therapy for HTLV-III/LAV infection becomes available, these children should be considered for such therapy. Knowledge that a child is infected will allow parents and other caretakers to take precautions when exposed to the blood and body fluids of the child. Adoption and foster-care agencies should consider adding HTLV-III/LAV screening to their routine medical evaluations of children at increased risk of infection before place- ment in the foster or adoptive home, since these parents must make decisions regard- ing the medical care of the child and must consider the possible social and psycholog- ical effects on their families. . Mandatory screening as a condition for school entry is not warranted based on availa- ble data. Persons involved in the care and education of HTLV-III/LAV-infected children should respect the child's right to privacy, including maintaining confidential records. The number of personnel who are aware of the child's condition should be kept at a mini- mum needed to assure proper care of the child and to detect situations where the potential for transmission may increase (e.g., bleeding injury). All educational and public health departments, regardless of whether HTLV-III/ LAV-infected children are involved, are strongly encouraged to inform parents, chil- dren, and educators regarding HTLV-III/LAV and its transmission. Such education would greatly assist efforts to provide the best care and education for infected children while minimizing the risk of transmission to others. References Scott GB, Buck BE, Leterman JG, Bloom FL, Parks WP. Acquired immunodeficiency syndrome in in- fants. N Engl J Med 1984,310:76-81. Thomas PA, Jaffe HW, Spira TJ, Reiss R, Guerrero IC, Auerbach D. Unexplained immunodeficiency in children. A surveillance report. JAMA 1984,252:639-44. Rubinstein A, Sicklick M, Gupta A, et al. Acquired immunodeficiency with reversed T4/T8 ratios in infants born to promiscuous and drug-addicted mothers. JAMA 1983,249:2350-6. 1. 2. 3 P-60 4 Oleske J, Minnefor A, Cooper R Jr, et al. Immune deficiency syndrome in children. JAMA 1983; 249:2345-9 5. Ziegler JB, Cooper DA, Johnson RO, Gold J. Postnatal transmission of AIDS-associated retrovirus from mother to infant. Lancet 1985,i:896-8. 6. CDC. Unpublished data. 7. Kaplan JE, Oleske JM, Getchell JP, et al. Evidence against transmission of HTLV-III/LAV in families of children with AIDS. Pediatric Infectious Disease (in press). 8. Lewin EB, Zack R, Ayodele A. Communicability of AIDS in a foster care setting. International Confer- ence on Acquired Immunodeficiency Syndrome (AIDS), Atlanta, Georgia, April 1985. 9. Thomas PA, Lubin K, Enlow RW, Getchell J. Comparison of HTLV-II serology, T-cell levels, and general health status of children whose mothers have AIDS with children of healthy inner city mothers in New York. International Conference on Acquired Immunodeficiency Syndrome (AIDS), Atlanta, Georgia, April 1985. 10. Fischl MA, Dickinson G, Scott G, Klimas N, Fletcher M, Parks W. Evaluation of household contacts of adult patients with the acquired immunodeficiency syndrome. International Conference on Ac- quired Immunodeficiency Syndrome (AIDS), Atlanta, Georgia, April 1985. 11. Friedland GH, Saltzman BR, Rogers MF, et al. Lack of household transmission of HTLV-IIl infection EIS Conference, Atlanta, Georgia, April 1985. 1985 Dec 6,34:721-26, 731-32 Recommendations for Assisting in the Prevention of Perinatal Transmission of Human T-Lymphotropic Virus Type lll/Lymphadenopathy-Associated Virus and Acquired Immunodeficiency Syndrome The information and recommendations in this document are intended to assist health-care providers and state and local health departments in developing procedures to prevent perinatal transmission of human T-lymphotropic virus type lll/lymphadenopathy-associated virus (HTLV-III/LAV), the virus that causes acquired immunodeficiency syndrome (AIDS). This document contains recommendations for providing counselling and, when indicated, testing for antibody to HTLV-III/LAV for women who are at increased risk of acquiring the virus and who are either pregnant or may become pregnant. It is important that these women know they are at risk, as well as know and understand their HTLV-III/LAV-antibody status, so they can make informed decisions to help prevent perinatally acquired HTLV-III/LAV. Through counselling, uninfected women can learn how to avoid becoming infected, and in- fected women can choose to delay pregnancy until more is known about perinatal transmission of the virus. If already pregnant, infected women can be provided information for managing the pregnancy and caring for the child. Currently available data indicate that most pediatric HTLV-III/LAV infections and AIDS are acquired perinatally from infected women, but additional studies are needed to better quantify the risk of transmission from an infected pregnant woman to the fetus or newborn. The recommendations below pertain to women. However, men who are HTLV-III/LAV- antibody positive should also be counselled regarding the risks of sexual and perinatal trans- mission, so they can refer for counselling and testing their sex partners who may be pregnant or considering pregnancy. BACKGROUND Pediatric AIDS Cases due to Perinatal Transmission. As of December 1, 1985, 217 (1%) of the 15,172 AIDS cases reported to CDC occurred among children under 13 years of age. Sixty percent of these children are known to have died. These 217 cases represent only the more severe manifestations of HTLV-III/LAV infection. Less severe manifestations, often de- scribed as AIDS-related complex (ARC), are not reported to CDC, so the number of children with clinically significant iliness attributable to HTLV-III/LAV infection is greater than the report- ed cases of pediatric AIDS. In addition, .a number of infected children are probably asymptomatic. Of the 217 reported pediatric AIDS patients, 165 (76%) have as their only known risk factor a mother belonging to a group with increased prevalence of HTLV-III/LAV infection. An addi- tional 18% of the pediatric cases are attributable to transfusions of blood or blood products, while risk factor information is missing or incomplete on the remaining 6%. Of the 217 children with AIDS, 48% had mothers who were intravenous (IV) drug abusers; 17% had mothers who were born in Haiti; and 10% had mothers who were sex partners of either IV drug abusers or bisexual men. Of the patients with perinatally acquired AIDS, 45% resided in New York City, while Florida and New Jersey accounted for an additional 32%. Mechanisms of Perinatal Transmission. It is believed that HTLV-III/LAV is transmitted from infected women to their fetuses or offspring during pregnancy, during labor and delivery, or perhaps shortly after birth. Transmission of the virus during pregnancy or labor and delivery is demonstrated by two reported AIDS cases occurring in children who had no contact with their infected mothers after birth. One was delivered by Cesarean section (7,2). Transmission of the virus after birth has been implicated in one case of HTLV-III/LAV infec- tion in a child born to a mother reported to have acquired the infection from a postpartum blood transfusion. Since she breastfed the child for 6 weeks, the authors suggested breast- feeding as the possible mode of transmission (3). Recently, HTLV-III/LAV has been isolated from the breast milk of infected women (4). Risk of Perinatal Transmission from Infected Mothers. The rate of perinatal transmission of HTLV-III/LAV from infected pregnant women is unknown; however, available data suggest a high rate. In one study of 20 infants born to infected mothers who had already delivered one infant with AIDS, 13 (65%) had serologic and/or clinical evidence of infection with HTLV- II/LAV several months after birth (5,6). Since these women were selected on the basis of having previously transmitted HTLV-III/LAV perinatally, this study may overestimate the aver- age risk of transmission for all infected pregnant women. Perinatal transmission from an infected mother to her newborn is not inevitable. Of three children born to women who became infected with HTLV-III/LAV by artificial insemination from an infected donor, all were in good health and negative for antibody to the virus more than 1 year after birth ( 7). Another child, born to a woman who was already pregnant at the time of AIDS diagnosis and was demonstrated to be viremic, was seronegative, culture negative, and healthy at birth and at 4 months of age (8). In a retrospective study evaluating nine children under 5 years of age whose mothers were later diagnosed with AIDS, two (22%) had antibody to HTLV-III/LAV (9). The infection status of these women during pregnancy was unknown. In these studies, the rate of transmission ranged from 0% (0/3) to 65% (13/20). Additional studies are needed to better define the rate of transmission and variables associated with it. Risk of lliness among Infected Pregnant Women. Pregnancy is associated with suppres- sion of cell-mediated immunity and increased susceptibility to some infections (70). The T- helper to T-suppressor ratio is decreased during normal pregnancy, being lowest in the third trimester, and returns to normal approximately 3 months postpartum (70). It is not known whether pregnancy increases an infected woman's risk of developing AIDS or ARC, but one study suggests it does (6). Fifteen infected women who were well at time of delivery were fol- lowed an average of 30 months after the births of their children. Five (33%) subsequently de- veloped AIDS; seven (47%) developed AIDS-related conditions; and only three (20%) remained asymptomatic. These results may not apply to all infected pregnant women, but they do sug- gest an increased likelihood of developing disease when an HTLV-III/LAV infection occurs in association with pregnancy. Prevalence of HTLV-III/LAV Infection. Counselling and testing for antibody to HTLV-III/ LAV, when indicated, to reduce perinatal transmission of AIDS will be most beneficial in popu- lations of women with increased prevalence of the virus (Table 1). These include: women who have used drugs intravenously for nonmedical purposes; women who were born in countries where heterosexual transmission is thought to play a majorrole (77,72); women who have en- gaged in prostitution; and women who are or have been sex partners of men who abuse IV drugs, are bisexual, have hemophilia, were born in countries where heterosexual transmission is thought to play a majorrole (717,72), or have evidence of HTLV-III/LAV infection. The prevalence of antibody to HTLV-III/LAV in U.S. populations of men and women ranges from less than 0.01% in female blood donors to as high as 74% in men with hemophilia (73-15). Among heterosexual IV drug abusers, the prevalence of HTLV-III/LAV infection ranges from 2% to 59% in various geographic areas (76,7 7). Seroprevalence among the hete- rosexual partners of persons at increased risk for AIDS varies from 10% in female partners of asymptomatic, seropositive hemophilia patients to 71% in the female partners of men with AIDS or ARC (78-20). Among prostitutes, the HTLV-III/LAV antibody prevalence varies from 57% to 40%, depending on geographic area, with most of the women with positive tests relat- ing histories of IV drug abuse (27). Among female blood donors in Atlanta, Georgia, who denied belonging to high-risk groups, 0.01% had repeatedly reactive enzyme-linked immuno- sorbent assays (ELISAs) followed by reactive Western blot tests (75). Commercially available tests to detect antibody to HTLV-III/LAV are ELISAs using antigens derived from whole disrupted HTLV-III/LAV. When the ELISA is reactive on initial testing, it is standard procedure to repeat the test on the same specimen. Repeatedly reactive tests are highly sensitive and specific for antibody to HTLV-III/LAV. However, when the ELISA is used to screen populations in which the prevalence of infection is very low (such as blood donors P-62 or women not in high-risk groups), the proportion of repeatedly reactive results that are falsely positive will be higher. For that reason, an additional test, such as a Western blot, is recom- mended following repeatedly reactive ELISA results, especially in low-prevalence populations. In populations with high prevalence of infection (e.g. homosexual men or IV drug abusers), most repeatedly reactive ELISAs are reactive by Western blot or another test. For example, among 109 IV drug abusers whose sera were repeatedly reactive by ELISA, over 85% were reactive by Western blot (22). In contrast, in a low-prevalence population of 69 female blood donors whose sera were repeatedly reactive by ELISA, only 5% were reactive by Western blot (15). Due to the seriousness of the implications of HTLV-IlI/LAV-antibody reactivity, it is recom- mended that repeatedly reactive ELISAs be followed by an additional test, such as the West- ern blot. Women with sera repeatedly reactive by ELISA and reactive by Western blot should have a thorough medical evaluation. HTLV-III/LAV has been isolated from a single specimen in 67%-95% of persons with specific antibody (23,24). Because infection has been demonstrated in asymptomatic persons, the presence of specific antibody should be consid- ered presumptive evidence of current infection and infectiousness. TABLE 1. Prevalence of HTLV-III/LAV antibody in heterosexual populations — United States No. Populations Location tested Prevalence (%) Intravenous drug New York City 274 59 abusers (716,17) NJ* < 5 miles from Nyct 204 56 NJ 5-10 miles from NYC 124 43 NJ > 100 miles from NYC 55 2 San Francisco 53 9 Persons with hemophilia (73,74) Factor VII concentrate recipients 234 74 Factor IX concentrate recipients 36 39 Cryoprecipitate only recipients 15 40 Female prostitutes (27) Seattle, Washington 92 5 Miami, Florida 25 40 Female sex partners of men with AIDS or ARC 42 47 (two separate studies) (79,20) 7 71 Female sex partners of men with asymptomatic HTLV-III/LAV infection (78) i 10 Haitians (72) New York City 97 4 Miami, Florida 129 8 Female blood donors (75) Atlanta, Georgia 28,354 0.01 ‘New Jersey. New York City. RECOMMENDATIONS Women Who Should be Offered Counselling and Testing. Counselling services and test- ing for antibody to HTLV-III/LAV should be offered to pregnant women and women who may become pregnant in the following groups: (1) those who have evidence of HTLV-III/LAV infec- tion; (2) those who have used drugs intravenously for nonmedical purposes; (3) those who were born in countries where heterosexual transmission is thought to play a major role (117,72); (4) those who have engaged in prostitution; (5) those who are or have been sex partners of: IV drug abusers, bisexual men, men with hemophilia, men who were born in coun- tries where heterosexual transmission is thought to play a major role (77,72), or men who otherwise have evidence of HTLV-III/LAV infection. If data become available to show that HTLV-III/LAV-antibody prevalence is increased in other groups or settings, counselling and testing programs should be extended to include them. Routine counselling and testing of women who are not included in the above-mentioned groups is not recommended due to low P-63 prevalence of infection and concern about interpretation of test results in a low-prevalence population. However if a woman requests it, the service should be provided in accordance with these recommendations. Settings for Offering Counselling and Testing. Counselling and testing for antibody to HTLV-III/LAV to prevent perinatal transmission is recommended in the setting of any medical service in which women at increased risk are commonly encountered. These include services for treating IV drug abuse (i.e, detoxification and methadone maintenance), comprehensive hemophilia treatment centers, sexually transmitted disease clinics, and clinics that serve female prostitutes. In addition, services related to reproduction, such as family planning and infertility services, gynecologic, premarital, or preconceptual examinations, and prenatal and obstetric services should also consider offering counselling and testing if high-risk women are seen at these facilities. Testing for antibody to HTLV-III/LAV should be performed with the woman's consent after counselling is provided regarding risk factors for infection, the inter- pretation of test results, the risks of transmission, and the possible increased likelihood of dis- ease among women infected with HTLV-III/LAV in association with pregnancy. The counsel- ling and testing must be conducted in an environment in which confidentiality can be assured. In settings where confidential counselling and testing cannot be assured, information should be provided and referrals made to appropriate facilities. Frequency of Testing. Detectable antibodies to HTLV-III/LAV may not develop until 2-4 months after exposure. This, and whether the woman is continuously exposed, should be taken into account when considering the need for, and frequency of, repeat testing. High-risk women should be offered counselling and testing before they become pregnant. During pregnancy, counselling and testing should be offered as soon as the woman is known to be pregnant. If the initial test is negative, repeat testing may be indicated near delivery to aid in the clinical management of the pregnant woman and newborn. If this final test is negative and the mother’s risk of exposure no longer exists, she may safely consider breastfeeding the child, and management of the child need not include the same concerns that would be ap- propriate if the woman had had a positive test or if she were at high risk and had not been tested at all. Counselling Women with Positive Results. Women with virologic or serologic evidence of HTLV-III/LAV infection should be counselled regarding their own risk of AIDS and the risk of perinatal and sexual transmission of HTLV-III/LAV. Infected women should be counselled to refer their sex partners for counselling and testing. If the partners of these women are not in- fected, both members of the couple should be counselled on how they may modify their sexual practices to reduce the risk of HTLV-lII/LAV transmission to the uninfected partner. In addition, the couple should be told not to donate blood, organs, or sperm and should be discouraged from using IV drugs and advised against sharing needles and syringes. When seeking medical or dental care for intercurrent illness, they should inform those responsible for their care of their positive antibody status so appropriate evaluation can be undertaken. Recommendations for providing information and advice to individuals infected with HTLV-III/LAV have been pub- lished (25) Infected women should be advised to consider delaying pregnancy until more is known about perinatal transmission of the virus. Pregnant infected women may require additional medical and social support services due to an enhanced risk of opportunistic infections and psychosocial difficulties during and after pregnancy. Obstetric-care providers should be alert to signs and symptoms of HTLV-III/LAV and related opportunistic infections in these pregnant women and to the need for specialized medical care. HTLV-III/LAV-infected women should be advised against breastfeeding to avoid postnatal transmission to a child who may not yet be infected. The child should receive follow-up pediatric evaluations to determine whether he/she has HTLV-IIl/LAV infection, and to diag- nose and treat promptly any diseases that may be secondary to HTLV-III/LAV infection. Recommendations for educating and providing foster care for infected children have been published (26) Counselling Women with Negative Test Results. A negative ELISA for HTLV-III/LAV an- tibody in women who have no clinical or laboratory evidence of HTLV-lII/LAV infection is evi- dence that they have probably not been infected. However, uninfected women who have sex partners with evidence of HTLV-III/LAV infection or with an increased risk of becoming infect- ed should be informed that sexual intercourse increases their risk of infection. These women should be informed of the risks associated with pregnancy if they become infected and ad- vised to consider delaying pregnancy until more is known about perinatal transmission of the virus or until they are no longer considered to be at risk for acquiring the virus. In addition to preventing pregnancy, the consistent and proper use of condoms can offer some protection against HTLV-III/LAV infection. P-64 High-risk women, even if seronegative, should be told not to donate blood or organs. To decrease their risk of becoming infected, IV drug abusers should be encouraged to seek treat- ment for their drug abuse. Persons counselling IV drug abusers should know that IV drug abuse is often strongly ingrained and compulsive. Despite educational efforts and encourage- ment for treatment, some addicts will continue to abuse drugs or relapse after treatment. If drug abuse continues, they should be advised not to share needles or syringes and to use only sterile equipment. Additional Considerations. These recommendations will be revised as additional informa- tion becomes available. It is recognized that provision of the recommended professional coun- selling, HTLV-III/LAV-antibody testing and associated specialized medical services will take time to implement and may stress available resources, particularly in public facilities, which are most greatly affected. Health-care providers, social-service personnel, and others involved in educating and caring for HTLV-III/LAV-infected persons should be aware of the potential for social isolation and should be sensitive to the need for confidentiality. They should be fa- miliar with federal and state laws, regulations, and policies that protect the confidentiality of clinical data and test results. Each institution should assure that specific mechanisms are in place to protect the confidentiality of all records and to prevent the misuse of information. Anonymous testing would not be appropriate if it prevents adequate counselling and medical follow-up evaluation. Hospital precautions for managing infected women and infants should be patterned after those for caring for patients with HTLV-III/LAV infection (27,28). Additional recommenda- tions will follow. DEVELOPMENT OF THESE RECOMMENDATIONS The information and recommendations contained in this document were developed and compiled by CDC and the U.S. Public Health Service in consultation with individuals represent- ing: the Conference of State and Territorial Epidemiologists, the Association of State and Ter- ritorial Health Officials, the American Public Health Association, the United States Conference of Local Health Officers, the American Medical Association, the American College of Obstetri- cians and Gynecologists, the American Academy of Pediatrics, the Planned Parenthood Feder- ation of America, the American Venereal Disease Association, the Division of Maternal and Child Health of the Health Resources and Services Administration, the National Institute on Drug Abuse of the Alcohol, Drug Abuse, and Mental Health Administration, the National Hemophilia Foundation, the Haitian Medical Association, the American Bar Foundation, and the Kennedy Institute of Ethics at Georgetown University. The consultants also included repre- sentatives of the departments of health of the areas with the largest number of perinatally transmitted pediatric AIDS cases: New York City, Florida, and New Jersey. These recommen- dations may not reflect the views of all individual consultants or the organizations they represented. References 1. Lapointe N, Michaud J, Pekovic D, Chausseau JP, Dupuy JM. Transplacental transmission of HTLV-IlI virus. [Letter] NEngl JMed 1985,312:1325-6. 2. Cowan MJ, Hellmann D, Chudwin D, Wara DW, Chang RS, Ammann AJ. Maternal transmission of ac- quired immune deficiency syndrome. Pediatrics 1984,73:382-6. 3. Ziegler JB, Cooper DA, Johnson RO, Gold J. Postnatal transmission of AIDS-associated retrovirus from mother to infant. Lancet 1985,i1:896-7. 4 Thiry L, Sprecher-Goldberger S, Jonckheer T, et al. Isolation of AIDS virus from cell-free breast milk of three healthy virus carriers. [Letter] Lancet 1985;ii:891-2. 5. Scott GB, Fischl MA, Klimas N, et al. Mothers of infants with the acquired immunodeficiency syn- drome: outcome of subsequent pregnancies. Atlanta, Georgia: International conference on acquired . immunodeficiency syndrome, April 14-17, 1985. 6. Scott GB, Fischl MA, Klimas N, et al. Mothers of infants with the acquired immunodeficiency syn- drome: evidence for both symptomatic and asymptomatic carriers. JAMA 1985,253:363-6 7. Stewart GJ, Tyler JPP, Cunningham AL, et al. Transmission of human T-lymphotropic virus type Ill (HTLV-II) virus by artificial insemination by donor. Lancet 1985;ii:581-4. 8 CDC. Unpublished data. 9. Thomas PA, Lubin K, Enlow RW, Getchell J. Comparison of HTLV-II serology, T-cell levels, and gener- al health status of children whose mothers have AIDS with children of healthy inner city mothers in New York. Atlanta, Georgia: International conference on acquired immunodeficiency syndrome, April 14-17,1985. 10. Weinberg ED. Pregnancy-associated depression of cell-mediated immunity. Rev Inf Dis 19846 814-31. 11. WHO. Acquired immune deficiency syndrome (AIDS). Report on the situation in Europe as of 31 December 1984. Weekly Epidemiological Record 1985,60:85-92 12. Castro KG, Fischl MA, Landesman SH, et al. Risk factors for AIDS among Haitians in the United States. Atlanta, Georgia: International conference on acquired immunodeficiency syndrome, April 14-17, 1985. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25, 26. 272. 28. Jason J, McDougal JS, Holman RC, et al. Human T-lymphotropic retrovirus type lll/lymphadenop- athy-associated virus antibody: association with hemophiliacs’ immune status and blood component usage. JAMA 1985; 253:3409-15 Gjerset GF, McGrady G, Counts RB, et al. Lymphadenopathy-associated virus antibodies and T cells in hemophiliacs treated with cryoprecipitate or concentrate. Blood 1985,66:718-20. CDC. Unpublished data. Spira TJ, Des Jarlais DC, Bokos D, et al. HTLV-III/LAV antibodies in intravenous drug abusers: com- parison of low and high risk areas for AIDS. Atlanta, Georgia: International conference on acquired im- munodeficiency syndrome, April 14-17, 1985. Weiss SH, Ginzburg HM, Goedert JJ, et al. Risk for HTLV-lIl exposure and AIDS among parenteral drug abusers in New Jersey. Atlanta, Georgia: International conference on acquired immunodeficien- cy syndrome, April 14-17, 1985. Kreiss JK, Kitchen LW, Prince HE, Kasper CK, Essex M. Antibody to human T-lymphotropic virus type Il in wives of hemophiliacs: evidence for heterosexual transmission. Ann Intern Med 1985; 102:623-6. Redfield RR, Markham PD, Salahuddin SZ, et al. Frequent transmission of HTLV-Ill among spouses of patients with AIDS-related complex and AIDS. JAMA 1985;253:1571-3. Harris CA, Cabradilla CD, Robert-Guroff M, et al. HTLV-III/LAV infection and AIDS in heterosexual partners of AIDS patients. Minneapolis, Minnesota: Twenty-fifth interscience conference on anti- microbial agents and chemotherapy, September 29-October 2, 1985. CDC. Heterosexual transmission of human T-lymphotropic virus type Ill/lymphadenopathy- associated virus. MMWR 1985,34:561-3. CDC. Unpublished data. Feorino PM, Jaffe HW, Palmer E, et al. Transfusion-associated acquired immunodeficiency syndrome: evidence for persistent infection in blood donors. N Engl J Med 1985;312:1293-6. Jaffe HW, Feorino PM, Darrow WW, et al. Persistent infection with human T-lymphotropic virus type l/lymphadenopathy-associated virus in apparently healthy homosexual men. Ann Intern Med 1985;102:627-30. CDC. Provisional Public Health Service inter-agency recommendations for screening donated blood and plasma for antibody to the virus causing acquired immunodeficiency syndrome. MMWR 1985,34:1-5. CDC. Education and foster care of children infected with human T-lymphotropic virus type Il/lymphadenopathy-associated virus. MMWR 1985;34:517-21. CDC. Acquired immune deficiency syndrome (AIDS): precautions for clinical and laboratory staffs. MMWR 1982,31:577-80. CDC. Recommendations for preventing transmission of infection with human T-lymphotropic virus type lll/lymphadenopathy-associated virus in the workplace. MMWR 1985,34:681-6, 691-5. Vill. WORLD HEALTH ORGANIZATION GUIDELINES 1985 May 17;34:275-76 World Health Organization Workshop: Conclusions and Recommendations on Acquired Immunodeficiency Syndrome An international conference on acquired immunodeficiency syndrome (AIDS), sponsored by the U.S. Department of Health and Human Services and the World Health Organization (WHO), was held in Atlanta, Georgia, April 15-17, 1985. It was attended by over 3,000 participants from 50 countries and was followed on April 18-19 by a WHO consultation to review the infor- mation presented at the conference and to assess its international implications. The group of WHO consultants concluded that information is now sufficient to permit health authorities to take actions that may decrease the incidence of AIDS among certain risk groups. The group submitted the following conclusions and recommendations: 1. WHO should: a. Establish a network of collaborating centers with special expertise in the field. The centers should assist in training staff members and providing reference panels of sera, evaluation of diagnostic tests, and provision of advice on the production of working reagents. They should also assist in preparing educational material and or- ganizing studies to determine the natural history of the disease and the extent of in- fection in different parts of the world. Coordinate global surveillance of AIDS using a compatible reporting format and the currently accepted case definition. WHO should disseminate these data and other important developments on the disease as widely and as rapidly as possible. Assist in developing an effective vaccine, and when appropriate, developing interna- tional requirements for the vaccines. WHO should take an active role in facilitating the evaluation of candidate vaccines. Encourage and assist in periodic serologic studies in countries where AIDS has yet to be recognized and should ensure the collection of comparable data and representa- tive selections of sera, since lymphadenopathy-associated virus/human T-lympho- tropic virus type lll (LAV/HTLV-lI) infection precedes AIDS in an individual or a com- munity, early recognition will require serologic studies in groups with potential risk of infections. 2. Member countries should: a. Inform the public that LAV/HTLV-IIl infection is acquired through heterosexual and homosexual intercourse, needle-sharing by intravenous drug abusers, transfusion of contaminated blood and blood products, transmission by infected mothers to their babies, and probably repeated use of needles and other unsterile instruments used for piercing skin/mucous membranes. Information should be provided about the risk of LAV/HTLV-IIl infection and AIDS, especially to those men and women who may be at increased risk because of multiple sexual partners. There is currently no evi- dence of spread of LAV/HTLV-IIl by casual social contact even within households. Provision of timely and accurate information on these points is recommended to allay inappropriate public concern. Ensure that health-care workers are informed about AIDS and LAV/HTLV-IIl infec- tion, modes of transmission, clinical spectrum, available programs of management (including psychosocial support), and methods for prevention and control. Assess the risk that AIDS poses tp each country’s population and establish methods of diagnosis, surveillance, and laboratory testing, including specific tests for LAV/ HTLV-II. Screen, where feasible, potential donors of blood and plasma for antibody to LAV/ HTLV-II, and not use positive units for transfusion or for the manufacture of products where there is a risk of transmitting infectious agents. Potential donors should be in- formed about the testing in advance of the donation. . Reduce the risk of transmission of LAV/HTLV-Ill by factor VIII and IX concentrates by treating them by heat or other proven methods of inactivation. The use of such products is recommended. P-68 f. Inform potential donors of organs, sperm, or other human material about AIDS, and encourage groups at increased risk of infection to exclude themselves from donat- ing. Whenever possible, serologic testing should be performed before these mate- rials are used. This is particularly important when donor material is collected from an unconscious or deceased patient on whom relevant information may be absent g. Refer individuals with positive tests for antibody to LAV/HTLV-Ill for medical evalua- tion and counseling. Such people should be encouraged to inform their health-care attendants of their status. h. Develop guidelines for the total care of patients and for handling their specimens in hospital and other settings. These guidelines should be similar to those that have been effective for care of patients with hepatitis B. i. Develop codes of good laboratory practice to protect staff against risk of infection. Such recommendations may be based on those found in the Laboratory Biosafety Manual published by WHO (7). The level of care required for work with specimens from patients infected with LAV/HTLV-IIl is similar to that required with hepatitis B. The use of class Il biologic safety cabinets is recommended. These cabinets are ade- quate for containment of other agents, such as herpes and hepatitis viruses, myco- bacteria, and protozoa, that may be present in the specimens. For work involving production and purification of LAV/HTLV-IIl, P3 biosafety containment levels must be employed. j. Collect and store serum samples from representative laboratory workers at the time of employment and at regular intervals thereafter, to be able to assess the risk of laboratory acquired infection and effectiveness of biosafety guidelines. Countries should provide this information to WHO for collation and dissemination. Provision of samples and testing should be carried out with the informed consent of the subjects. k. Be aware of the importance of keeping confidential information about the results of serologic testing and the identity of AIDS patients. Serologic testing should be un- dertaken with the informed consent of the subject. Abstracted from WHO Weekly Epidemiological Record 7985,60:129-39. Reference 1. WHO. Biological safety. Weekly Epidemiological Record 1983;58:289-90. 6900031018713 P-69 AAV AIDS ARC ARV CAT CDC CMV CNS CT DNA EBV EIA ELISA HBV HIV HTLV IL1,IL2 LV. LAV RNA STD List of Abbreviations AIDS associated virus acquired immunodeficiency syndrome AIDS-related complex AlIDS-associated retrovirus computerized axial tomography Centers for Disease Control cytomegalovirus central nervous system computed tomography deoxyribonucleic acid Epstein-Barr virus enzyme immunoassay enzyme linked immunosorbent assay hepatitis B virus human immunodeficiency virus human T-cell lymphotropic virus interleukin 1, interleukin 2 intravenous lymphadenopathy-associated virus ribonucleic acid sexually transmitted disease G-1 Glossary acquired immunodeficiency syndrome (AIDS). A severe manifestation of infection with human immunodeficiency virus; characterized by opportunistic infections and Kaposi's sarcoma. active surveillance. The process of actively seeking out and identifying health problems within a population. agglutinate. To form clumps; especially the clumping of bacteria caused by certain antibodies. AIDS. See acquired immunodeficiency syndrome. AIDS associated retrovirus (ARV). Name given by researchers at the University of California at San Francisco to isolates of the retrovirus that causes AIDS. See also human immunodeficiency virus. AIDS-related complex (ARC). A variety of chronic symptoms and physical abnormalities that occur in some persons who are infected with HIV but do not meet the Centers for Disease Control's definition of AIDS. Symptoms may include chronically swollen glands, recurrent fevers, weight loss, chronic diarrhea, lethargy, immune system changes (less severe than in AIDS), and oral thrush. ARC may or may not develop into AIDS. See also lymphadenopathy syndrome. anemia. Deficiency of either hemoglobin (oxygen-carrying pigment) or red blood cells in circulating blood. anergy. Total loss of normal reactivity. adj., anergic. antibody. A protein in the blood produced in response to exposure to specific foreign molecules (antigens). Antibodies neutralize toxins and interact with other components of the immune system to eliminate infectious microorganisms from the body. antigen. A substance that stimulates the production of antibodies. adj., antigenic (n.), antigenicity ability of a substance to stimulate antibody formation. ARC. See AIDS-related complex. ARV. See AIDS-associated retrovirus. atrophy. Wasting; decrease in normal size of organ or tissue. B cells (B lymphocytes). Types of white blood cells that produce antibodies in response to stimulation by an antigen. bronchoalveolar lavage. Washing of the bronchial tubes and air sacs in the lungs to obtain specimens for diagnostic investigation. bronchoscopy. ~~ Visual inspection of the trachea (windpipe) and bronchi with a bronchoscope. G-2 Candida albicans. A yeastlike fungus. Infection of the mouth with this organism causes whitish sores, which in AIDS patients often extend into the esophagus. See also candidiasis, thrush. candidiasis. Infection caused by Candida albicans; may occur on any mucosal surface or in the blood. See also thrush. case-control study. An epidemiologic study design that matches cases (individuals with a disease or health problem) with controls (persons who do not have that condition). Matching maybe done by age, race, socioeconomic status, occupation, and area of residence. Comparisons are made between the two groups, with the controls representing the norm or a known bias. cell-mediated immunity. An immune system defense mechanisn involving the coordinated activity of two subpopulations of T-lymphocytes, helper T cells, and suppressor T cells. See also humoral immunity. clotting factors. Factors essential to normal blood clotting. Twelve such factors (designated I through XII) have been identified. See also hemophilia. CMV. See cytomegalovirus. cofactor. A factor that, when present together with the basic causative agent of a disease, increases the likelihood that the disease will develop. Cofactors may include the presence of other microorganisms or physchosocial factors, such as stress. cohort. A group of individuals or vital statistics about them having a statistical factor in common (e.g., year of birth). computed tomography (CT). A computer-assisted X-raying of a selected level or section of the body. computerized axial tomography (CAT). See computed tomography. cortisol. A hormone, also called hydrocortisone, with antiinflammatory action. cryoprecipitate. A frozen preparation, specifically of blood cells or factors, e.g., clotting factors. cryptococcosis. A fungal infection. See also Cryptococcus neoformans. Cryptococcus neoformans. A yeastlike fungus, agent of cryptococcosis. Cryptosporidium. A protozoan parasite that causes severe, protracted diarrhea. In AIDS patients, the diarrhea often becomes chronic (lasting longer than | to 2 weeks) and may lead to severe malnutrition. cytomegalovirus (CMV). A type of herpesvirus. Before the appearance of AIDS, it was associated with congenital infection of infants and of immunosuppressed (e.g., for transplantation) patients; it rarely causes disease in healthy adults. In AIDS patients, CMV may produce pneumonia and inflammation of the retina, liver, kidneys, and colon. cytopathic. Causing disease-induced or disease-inducing changes to cells. cf. cytotoxic. G-3 cytotoxic. Having a deleterious effect on cells; cell killing. (n.), cytotoxicity. cf. cytopathic. dementia. Progressive mental deterioration due to organic disease of the brain. adj., demented. deoxyribonucleic acid (DNA). (i) a nucleic acid found chiefly in the nucleus of living cells that encodes genetically transmissable characteristics. (ii) DNA virus: a virus that encodes its genetic informtion in DNA. See also ribonucleic acid. diagnosis. Determination of the cause of the disease causing symptoms in a patient. cf. prognosis. direct/indirect immunofluorescence tests. The use of fluorescein-labeled antibodies to identify antigenic material specific for the labeled antibody. DNA. See deoxyribonucleic acid. EBV. See Epstein-Barr virus. EIA. See enzyme immunoassay. ELISA. See enzyme-linked immunosorbent assay. encephalitis. Inflammation of the brain. cf. encephalopathy. encephalopathy. Any degenerative disease of the brain. cf. encephalitis. endoscopy. Use of an instrument to visually examine the interior structures of the body. enzyme immunoassay (EIA). See also enzyme-linked immunosorbent assay. enzyme-linked immunosorbent assay (ELISA). A test used to detect antibodies in blood samples. Results are usually reported as titers (concentrations). See also enzyme immunoassay. epidemiology. The scientific study of the frequency and distribution of infectious diseases in humans; the process of identifying how, when, and where new agents and infections arose and how they were spread. Epstein-Barr virus (EBV). A type of herpesvirus; the principal course of infectious mononucleosis in young adults. [t has been implicated as a factor in the development of Burkitt's lymphoma (proliferative disease of lymphoid tissue) in Africa. etiology. The cause or course of a disease. false-negative. A negative test result for a condition that is in fact present. cf. false-positive. false-positive. A positive test result for a condition that is in fact not present. cf. false-negative. G-4 fibrosarcoma. A cancerous tumor composed of fibrous, connective tissue. fisting. A sexual practice in which one partner inserts a fist into the other's anus. gonorrhea. A sexually transmitted disease caused by Neisseria gonorrhoeae. granulocytopenia. Deficiency of granulytes (types of blood cells, e.g., neutrophils) in the blood. HBV. See hepatitis B virus. helper /suppressor T-cell ratio. The ratio of helper T cells to suppressor T cells in the blood. In AIDS and ARC patients, this ratio is often abnormally low because there are fewer helper T cells; referred to as "reversed" or "inverted" t-cell ratio. helper T cells. A type of T cell, also called helper/inducer lymphocytes; they play important immunoregulatory roles. These cells appear to be the primary targets for infection by HIV. hemophilia (A and B). A rare, hereditary bleeding disorder of males, caused by a deficiency in the ability to make one or more blood-clotting factors. h. A, deficient in factor VIII; h. B, deficient in factor IX. ‘hepatitis (A and B). Inflammation of the liver due to infection with hepatitis virus type A or B. hepatitis B virus (HBV). Virus causing chronic infection of the liver; agent of hepatitis B. hepatomegaly. Abnormal enlargement of the liver. herpes simplex virus (HSV) types | and 2. A type of herpesviris that causes blisters, often painful, to form, especially on the edges of the lips (cold sore) or on the genitals. herpesviruses. A group of viruses that includes the herpes simplex viruses, varicella- zoster virus, CMV, and EBV. histology. Microscopic study of the form and structure of living tissues. adj., histological. HIV. See human immunodeficiency virus. HLA. See human leukocyte antigens. homeostasis. Stability in the normal body state of an organism; the process of reaching that stability. HSV. See herpes simplex virus. human immunodeficiency virus (HIV). The name proposed for the causative agent of AIDS by a subcommittee of the International Committee on the Taxonomy of Viruses to replace the many names now current, including HTLV, LAV, AAV, and ARV. human leukocyte antigens (HLA). Tissue transplantation compatibility antigens controlled by the genes at the HLA chromosome locus. G-5 human T-cell lymphotropic virus (HLTV), type Ill. The name given by researchers at the National Cancer Institute to isolates of the retrovirus that causes AIDS. Also, HLTV-IL. See also human immunodeficiency virus. HLTV. See human T-cell lymphotropic virus. humoral. Present in or acting through a body fluid. humoral immunity. The immune system defense mechanism that involves the production of antibodies and associated molecules present in body fluids such as serum and lymph. cf. cell-mediated immunity. hyperplasia. Increase in volume of a tissue or organ caused by the formation and growth of new cells. See also neoplasm. ajd., hyperplastic. hypoglycemia. Deficiency of sugar in the blood. IL1, [IL2. See interleukin. immune system. The natural system of defense mechanisms, by which specialized cells and proteins in blood and other body fluids work together to eliminate disease-producing microorganisms and other foreign substances. immunogenicity. The ability of a substance to induce specific resistance (e.g., a vaccine is immunogenic). adj., immunogenic. (n.), immunogen. immunoglobulins (A,E,G,M). Proteins having antibody activity and related proteins with similar antigenic specificity. Specific immunoglobulins may be produced in response to specific infections. immunoregulatory. Causing the immune system to react to the introduction of microorganisms or foreign substances. immunosuppression. A state in which the immune system is suppressed, whether intentionally (e.g., to allow an organ or tissue to be transplanted) or as part of a pathological process. ajd., immunosuppressed. incidence. The rate at which a certain event occurs, as the number of new cases of a specific disease occurring during a certain period. cf. prevalence. inflammation. Swelling; response of tissue to injury or destruction of cells. in situ. In its normal place; at the site of origin. interferon (alpha, beta, gamma). A class of proteins important in immune function and known to inhibit certain viruses. interleukin (1 and 2). A substance produced by T cells that stimulates T cells and some B cells to proliferate. IL2 is also known as T-cell growth factor. G-6 interstitial pneumonitis. Localized acute inflammation of the lung. i.p. persisting for more than 2 months in a child under 13 years of age is indicative of AIDS unless another cause Is identified or tests for HIV are negative. in utero. Occurring in the uterus, i.e., before birth, during gestation. in vitro. In glass, i.e., in a test tube of other artificial environment. cf. in vivo. in vivo. Within a living body. cf. in vitro. Kaposi's sarcoma (KS). A cancer or tumor of the blood and lymphatic vessel walls. It usually appears as blue-violet to brownish skin blotches or bumps. Before the appearance of AIDS, it was rare in the United States and Europe, where it occurred primarily in men, usually of Mediterranean origin, over age 50 or 60. AlDS-associated KS is much more aggressive than the classic form. KS is one of the CDC's criteria for the diagnosis of AIDS. KS. See Kaposi's sarcoma. LAS. See lymphadenopathy syndrome. LAV. See lymphadenopathy-associated virus. lectin. A class of plant substances that cause blood to form clumps, or agglutinate. leukemia. Fatal disease, with marked increases in the number of leukocytes. leukocytes. White blood cells, components of the immune system; include lymphocytes and four other types. leukopenia. Deficiency of leukocytes in the blood. lymphadenopathy (persistent generalized lymphadenopathy, PGL). Lymph node disease. PGL, chronic disease at more than two lymph node sites. See also lymphadenopathy syndrome. lymphadenopathy-associated virus (LAV). Name given by French researchers to the first reported isolate of the retrovirus now known to cause AIDS, recovered from a person with lymphadenopathy who was also in the group at high risk for AIDS. See also lymphadenopathy syndrome, human immunodeficiency virus. lymphadenopathy syndrome (LAS). A syndrome characterized by chronic swelling of lymph nodes at one or more sites. lymphocyte. A variety of leukocyte. See also T cells, B cells. lymphocytopenia. Reduction in the number of lymphocytes in the blood. lymphoma. Tumor of lymphoid tissue, or collection of lymph producing a tumorlike swelling or mass. lymphopenia. See lymphocytopenia. G7 lymphoproliferation. Multiplication of lymphoid tissue. adj., lymphoproliferative. lymphoproliferative disorder. Proliferation of immune system cells, generally an autoimmune or autoallergic condition. meninges. Membranes covering the brain and spinal cord. adj., meningeal. meningitis. Inflammation of the meninges. metastasis. Spread of disease, especially cancer, from one organ or part of the body to another. adj., metastatic. (v.), metastasize. mitogen. An agent that induces cell division. adj., mitogenic. monoclonal antibody. An antibody derived from a single clone of cells. A clone is a colony grown from a single ancestor cell; every cell in a clone is genetically identical (barring spontaneous mutation). mononucleosis, infectious. Disease characterized by lymphadenopathy and increased lymphocytes in the blood, caused by Epstein-Barr virus. morbidity. Condition of being diseased; sickness or illness. mucocutaneous. Pertaining to mucous membrane and skin. mycobacteria (Mycobacterium avium-intracellulare, Mycobacterium tuberculosis). Members of the genus Mycobacterium, which are responsible for leprosy (M. leprae) and tuberculosis (M. tuberculosis), among others. M. avium-intracellulare may cause a disseminated disease that responds poorly to therapy in AIDS patients. neoplasm. Mass of newly formed tissue; new growth (tumor). adj., neoplastic. neuropathy. Any disease of the nervous system. neutropenia. Diminished number of neutrophils (a type of leukocyte) in the blood. Ol. See opportunistic infection. opportunistic infection. Any infection caused by a microorganism that rarely causes disease in persons with normal immune function. Ols are among the CDC criteria for the diagnosis of AIDS. papillomavirus. Family of viruses which includes those causing growths and warts of the skin or mucous membrane. parenteral. Involving introduction directly into the bloodstream; intravenous. passive surveillance. The process of monitoring health problems through the receipt of reports and data. cf. active surveillance. pathogen. Any disease-producing agent or microorganism. ad)., pathogenic. (n.), pathogenesis. pathogenesis. The development of disease; the process by which a disease state develops. PGL. See lymphadenopathy. phenotype. The outward, apparent characteristics of an organism's hereditary constitution (e.g., being blue-eyed or brown-eyed is a phenotype); a reflection of the genetic information in the cells. phytohemagglutinin. A plant substance that will agglutinate blood cells. Pneumocystis carinii. A parasite, agent of P. carinii pneumonia,the most common life- threatening opportunistic infection diagnosed among AIDS patients. polyclonal. Representing many individual clones. prevalence. The number of cases of a specific disease in existence in a given population at a certain time or period. cf. incidence. prodrome. Warning symptoms; a set of symptoms that precede the development of fullblown disease. adj., prodromal. prognosis. The probable outcome of a disease. cf. diagnosis. proliferation. Multiplication of similar cells. prospective study. A study that involves the collection of observations after the investigation is started to measure characteristics and wait for disease to develop. cf. retrospective study. radioimmunoassay (RIA). A method of analysis, such as determination of the concentra- tion of substances in blood plasma, through the use of radioactive antibodies. retrospective study. A study that uses observations that have been collected in the past and attempts to measure past characteristics in persons already diseased. cf. prospective study. retrovirus. A class of RNA viruses that have the ability to copy the RNA into DNA inside an infected cell. The resulting DNA is incorporated into the genetic structure of the cell in a form called a provirus. See also reverse transcriptase. reverse transcriptase. An enzyme produced by retroviruses that allows them to produce a DNA copy of their RNA, the first step in their reproductive cycle. G-9 RIA. See radioimmunoassay. ribonucleic acid. (i) a nucleic acid that generally transcribes the information encoded by the DNA and translates it into specific proteins and other substances. (ii) RNA virus; a virus that carries its genetic information encoded as RNA instead of DNA. See also retrovirus. risk factors. Circumstances or characteristics that put one at risk for a disease or condition. Risk factors for AIDS include male homosexuality, intravenous drug use, Haitian origin, and receipt (transfusion) of blood or blood products. RNA. See ribonucleic acid. sensitivity. The ability of a test to determine true positives, i.e., to give a positive result for persons who are in fact positive for the condition being tested. cf. specificity. sepsis. Presence of pathogenic bacteria disseminated throughout the body. adj., septic. seroconversion. The initial development of antibodies specific to a particular antigen; L.e., time of conversion from being seronegative to being seropositive. seroepidemiology. An epidemiological study conducted by testing serum samples, both fresh and stored, for a period of months to years. seronegative. No antibodies found in the serum. seropositive. Antibodies present in the serum. shooting gallery. A place where intravenous drug users gather to inject (shoot) drugs; Injection equipment is often rented or shared. single radial immunodiffusion. A method of quantifying immunoglobulins in agar plates. specificity. The ability of a test to determine true negatives, i.e., to give a negative result for persons who are in fact negative for the condition being tested. splenomegaly. Abnormal enlargement of the spleen. suppressor T cells. A class of lymphocytes with important regulatory and functional roles in the human immune system; they destroy cells infected with viruses or other microorganisms. syndrome. A pattern of symptoms or signs, appearing one by one or simultaneously, that together characterize a particular disease or disorder. synergism. Joint action in which the combined effect is greater than the sum of the individual parts. syphilis. A sexually transmitted disease caused by Treponema pallidum. G-10 T cells. A class of lymphocytes that mature in the thymus gland. Subsets of T cells have a variety of specialized functions within the immune system. See also B cells, helper T cells, suppressor T cells. thrush. Infection of the oral mucous membrane by Candida albicans. See also candidiasis. Toxoplasma gondii. A protozoan parasite that is one of the most common causes of inflammation of the brain in AIDS patients. See also toxoplasmosis. toxoplasmosis. Infection with Toxoplasma gondii. trauma. A wound or injury, especially damage produced by an external force. Treponema pallidum. The causative agent of syphilis. varicella-zoster virus. A type of herpesvirus, the cause of chicken pox and shingles. viremia. The presence of virus in circulating blood, which implies active viral replication. virion. A complete virus particle. Western blot. A test that identifies antibodies against specific proteins. Believed to be more specific than the ELISA in detecting antibodies to HIV in serum; it is also more difficult to perform and much more expensive. Used most often to confirm that samples testing positive by ELISA are in fact positive. Willebrand's disease. Hereditary deficiency of antihemophilic globulin with capillary defect, a form of hemophilia. works. Injection equipment for intravenous drug use. G-11 PHS AGENCY RESOURCE CONTACTS ON AIDS Office of the Assistant Secretary For Health Ms. Sandra Bart PHSAIDS Coordinators Office 200 Independence Avenue, NW Room 740, HHH Building Washington, DC 20212 Phone: (202) 472-4248 Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA) Dr. Frederick Goodwin Director of Intramural Research National Institute of Mental Health 9000 Rockville Pike Building 10, Room 4N224 Bethesda, MD 20892 Phone: (301) 496-3501 Centers for Disease Control Dr. Walter Dowdle Deputy Director (AIDS) 1600 Clifton Road, NE Building 1, Room 2122 Atlanta, GA 30333 Phone: (404) 329-1374 Food and Drug Administration Dr. Paul Parkman Acting Director Center for Drugs & Biologics Room 1534, Parklawn Building 5600 Fishers Lane Rockville, MD 20857 Phone: (301) 443-2894 Health Resources & Services Administration (HESA) Dr. Samuel Matheny Director, AIDS Services Program 5600 Fishers Lane Room 9-13 Rockville, MD 20857 National Institutes of Health (NIH) Ms. Wendy Liffers Deputy Assistant to Director, NIAID 9000 Rockville Pike Building 31, Rcom 7A04 Bethesda, MD 20892 Phone: (301) 496-9088 Health Care Financing Administration Dr. William Winkenwerder Special Assistant to the Administrator 200 Independence Avenue, SW Room 314G, HHH Building Washington, DC 20212 Phone: (202) 245-8502 ASTHO AIDS COMMITTEE Kristine Gebbie, R.N., Chair Department of Human Resources 825 State Office Building, Box 231 Portland, OR 97207 Lloyd F. Novick, M.D. New York State Health Department Governor Nelson Rockefeller Empire Corning Tower Building, Room 1492 Albany, NY 12237 Molly J. Coye, M.D., MPH Department of Health CN 350 Trenton, NJ 08625 Sister Mary Madonna Ashton Department of Health 717 Delaware Street, SE Minneapolis, MN 55440 Donald Lyman, M.D. Department of Health 714 P Street Sacramento, CA 95814 Robert Bernstein, M.D. Texas Department of Health 1100 West 49th Street Austin, TX 78756 Representative of Health Education Lynn Mulder Director of Health Promotion Florida Department of Health 1317 Winewood Boulevard Tallahassee, FL 32301 Representative of Laboratory William J. Hausler, Jr. University of Iowa Hospitals Oakdale Campus [owa City, [A 52242 Representative of Epidemiology Dale Morse, M.D. New York Department of Health Governor Nelson A. Rockefeller Empire Corning Tower Building Albany, NY 12237 AIDS STATE CONTACT LIST Alabama Wallace E. Birch, D.V.M. Department of Public Health State Office Building, Room 900 501 Dexter Avenue Montgomery, AL 36130-1701 (205) 261-5131 Alaska John Middaugh, M.D. Office of Epidemiology Frontier Building, 3601 C Street P.O. Box 6333, Suite 540 Anchorage, AK 99502-0333 (907) 561-4406 Arizona Lloyd F. Novick, M.D. Arizona Department of Health Services 1740 West Adams Phoenix, AZ 85007 (602) 255-1024 Arkansas Tom McChesney, D.V.M. Arkansas Department of Health 4815 West Markham Little Rock, AR 72205 (501) 661-2597 California Robert E. Anderson, M.D. California State Department of Health Services P.O. Box 160146 Sacramento, CA 90816-0146 (916) 445-0553 Colorado Nancy Spencer Colorado Department of Health 4210 East 11th Avenue Denver, CO 80220 (303) 331-8320 Connecticut Matthew Cartter, M.D. State of Connecticut Department of Health Services 150 Washington Street Hartford, CT 06106 (203) 566-5058 Delaware Paul Silverman, D.P.H. Division of Public Health Robbins Building 802 Silver Lake Plaza Dover, DE 19901 (302) 736-5617 District of Columbia Lankford Hicks Department of Human Services 1875 Connecticut Avenue, N.W. Room 825 Washington, DC 20009 (202) 673-3525 Florida Gary J. Clarke Health Program Office, Building 1 1317 Winewood Boulevard, Room 115 Tallahassee, FL 32301 (904) 487-2945 Georgia Margaret Draganac Georgia Department of Human Resources 878 Peachtree Street, NE Atlanta, GA 30309 (404) 894-6527 Hawaii Don Cowne Hawaii Department of Health 3627 Kilauea Avenue Honolulu, HI 96816 (808) 735-5303 AIDS STATE CONTACT LIST (continued) Idaho Charles Brokopp, M.D. Department of Health and Welfare Division of Health, State House Boise, ID 83720 (208) 334-4309 [Illinois Russell J. Martin, D.V.M. Illinois Department of Public Health 535 West Jefferson Street Springfield, IL 62761 (217) 782-2016 Indiana Deborah Taylor Indiana State Board of Health 1330 West Michigan Street Indianapolis, IN 46206 (317) 633-8406 [owa Don Ruberti Iowa Department of Health Lucas State Office Building Des Moines, IA 50319 (515) 281-4936 Kansas Robert French Kansas Department of Health and Environment Forbes Field Topeka, KN 66620 (913) 862-9360 Ext. 481 Kentucky Reginald Finger, M.D., MPH Department for Health Services 275 East Main Street Frankfort, KY 40621 (502) 564-4478 Louisiana Susan Hassig Department of Health & Human Services P.O. Box 60630 New Orleans, LA 60630 (504) 568-5013 Maine Dave Akers Maine Department of Health 157 Capitol Street, State House #11 Augusta, ME 04333 (202) 289-3591 Maryland Scott Stamford Department of Health & Mental Hygiene 201 West Preston Street, 5th Floor Baltimore, MD 21201 (301) 225-6707 Massachusetts George Grady, M.D. State Laboratory Institute 305 South Street Jamaica Plain, MA 02130 (617) 522-3700 Michigan William Hall, M.D. Michigan Department of Health P.O. Box 30035 Lansing, MI 48909 (517) 373-1396 Minnesota Dorothy Reier Minnesota State Health Department 717 S.E. Delaware Street Minneapolis, MN 55440 (612) 623-5414 AIDS STATE CONTACT LIST (continued) Mississippi Bruce T. Brackin, MPH Mississippi State Department of Health P.O. Box 1700 Jackson, MS 39215-1700 (601) 354-6660 or (601) 354-6650 Missouri Raymond L. Bly Missouri Department of Health 1730 East Elm Street Jefferson City, MO 65101 (314) 751-2335 Montana Judith Gedrose, R.N., M.N. Department of Health and Environmental Sciences Cogswell Building Helena, MO 59620 (406) 444-5580 Nebraska Paul A. Stoesz, M.D. Nebraska Department of Health 301 South Centennial Mall P.O. Box 95007 Lincoln, NE 68509-5007 (402) 471-2937 Nevada George E. Reynolds, M.D. Bureau of Regulatory Health Services 505 East King Street, Room 202 Carson City, NV 89710 (702) 885-4475 New Hampshire Joyce Cournoyer New Hampshire Division of Public Health Services Health & Human Services Building, Hazen Drive Concord, NH 03301 (603) 271-4477 New Jersey Kenneth Black New Jersey State Department of Health CN 360 Trenton, NJ 08625 (609) 588-3520 New Mexico Linda Stoffel Health & Environmental Department P.O. Box 968 Santa Fe, NM 87504-0968 (505) 827-2615 New York Dale L. Morse, M.D., M.S. New York State Department of Health 651 Tower Building Empire State Plaza Albany, NY 12237 (518) 474-2011 North Carolina Rebecca Meriwether, M.D. North Carolina Division of Health Services P.O. Box 2091 Raleigh, NC 27602 (919) 733-3419 North Dakota James Pearson, M.D. North Dakota State Department of Health Capitol Building Bismarck, ND 58505 (701) 224-2378 Ohio Thomas J. Halpin, M.D., MPH Ohio Department of Health 246 North High Street Columbus, OH 43215 (614) 466-4643 AIDS STATE CONTACT LIST (continued) Oklahoma Dr. Greg Istre Oklahoma State Department of Health 1000 NE Tenth Street Oklahoma City, OK 73152 (405) 271-4200 Oregon Laurence R. Foster, M.D. Office of Health Status Monitoring P.O. Box 231 Portland, OR 97207 (503) 229-5792 Pennsylvania Robert Gens, M.D. Pennsylvania Department of Health P.O. Box 90 Harrisburg, PA 17108 (717) 787-6923 Rhode Island Richard A. Keenlyside, M.D. Rhode [sland Department of Health 75 David Street Providence, RI 02908 (401) 277-2362 South Carolina Richard L. Parker, D.V.M., M.P.H. SC DHEC 2600 Bull Street Columbia, SC 29201 (803) 758-7970 South Dakota Ken Senger South Dakota Department of Health 523 East Capitol Pierce, SD 57501 (605) 773-3364 Tennessee Gary Swinger, D.V.M. Department of Health & Environment 344 Cordell Hull Building Nashville, TN 37219 (615) 741-7247 Texas Charles Alexander, M.D. Texas Department of Health 1100 West 49th Austin, TX 78756 (512) 458-7304 Utah Craig R. Nichols, M.P.A. Utah Department of Health P.O. Box 45500 Salt Lake City, UT 84145-0500 (801) 533-6191 Vermont Richard A. Vogt, M.D. Vermont Department of Health 60 Main Street, Box 70 Burlington, VT 05402 (802) 863-7240 Virginia A. Martin Cader, M.D. Virginia Department of Health 109 Governor Street Richmond, VA 23219 (804) 786-6261 Washington William Lafferty, M.D. Department of Social & Health Services State of Washington - Mailstop: B17-9 Seattle, WA (206) 361-2831 AIDS STATE CONTACT LIST (continued) West Virginia David K. Heydinger, M.D. West Virginia Department of Health 1800 Washington Street, East Charleston, WV 25305 (304) 348-2971 Wisconsin Jeffrey P. Davis, M.D. Wisconsin Division of Health P.O. Box 309 Madison, WI 53701-0309 (608) 267-9003 Wyoming Roger Burr Health & Medical Services Hathaway Building Cheyenne, WY 82002 (307) 777-7953 CONTACTS OUTSIDE THE UNITED STATES Guam Charles P. Crisostomo, M.P.H. Department of Public Health & Social Services P.O. Box 96910 Agana, Guam 96910 (671) 734-2946 or (671) 734-2897 Puerto Rico Rafael Rivera Castano, M.D., M.P.H. Latin American Center for Sexually Transmitted Diseases Call Box STD Caparra Heights, Puerto Rico 00922 (809) 754-8118 or (809) 754-8128 Virgin Islands [saac Osborne, M.D. St. Thomas Hospital P.O. Box 7309 St. Thomas, Virgin Islands 00801 LOCAL AIDS EDUCATION & SERVICE ORGANIZATIONS Paula Van Ness, Executive Director AIDS Project Los Angeles 3670 Wilshire Boulevard, Suite 300 Los Angeles, CA 90010 (213) 738-8200 James W. Dilley, M.D. Project Administrator AIDS Health Project P.O. Box 0884 San Francisco, CA 94143 (415) 626-6637 Tim Wolfred, Executive Director San Francisco AIDS Foundation 333 Valencia Street, 4th Floor San Francisco, CA 94103 (415) 864-4376 Ann E. McFarren, Executive Director AIDS Action Council 729 8th Street, SE, #300 Washington, DC 20003 (202) 547-3101 Paul Kawata National AIDS Network 1012 14th Street, Suite 601 Washington, DC 20005 (202) 547-3101 Monsignour Fred Tondalo AID Center One P.O. Box 8152 Fort Lauderdale, FL 33310 (305) 764-3123 1-800-325-5371 Ms. Sally Dodds, Executive Director Health Crisis Network P.O. Box 52-1546 Miami, FL 33152 (305) 326-8833 Ken South AID Atlanta 811 Cypress Street, NW Atlanta, GA 30308 (404) 872-0600 Maury Weil The Georgia AIDS Action Committee P.O. Box 7482 Atlanta, GA 30357 (404) 894-6356 Iccie Patrick Chicago AIDS Foundation 845 North Michigan, Suite 903E Chicago, IL 60611 (312) 988-9005 Larry Kessler AIDS Action Committee 661 Boylston Street, Suite 4 Boston, MA 02116 (617) 437-6200 Nina Firestone ASP/SEMGA 17520 Woodward Avenue Detroit, MI 48203 (313) 869-5105 Mr. Allen Krafitz NJ Lesbian & Gay AIDS Awareness 268 High Street Newark, NJ 10702 (201) 596-0767 Paul A. Moore, Deputy Director AIDS Institute New York State Department of Health Corning Tower, #1921 Albany, NY 12237 (518) 473-0641 Gail Barouh Long Island AIDS, Inc. P.O. Box 2859 Huntington Street Long Island, NY 11746 (516) 385-2451 Doug Doran AIDS Resource Center (ARC) P.O. Box 792, Chelsea Station New York, NY 10011 (212) 206-1414 Richard D Gay Men's 132 West 2 New York, (212) 807-6 Ron Vacho New York Office of 125 Worth New York, (212) 566-4 Anna Forbe Action AID 330 South 1 Philadelphi (215) 732-2 Ms. France PCHA - Ph P.O. Box 12 Walnut Stre Philadelphiz (215) 545-86 Mike Richart Dallas Gay P.O. Box 19 Dallas, TX LOCAL AIDS EDUCATION & SERVICE ORGANIZATIONS (continued) inne, Executive Director Health Crisis, Inc. 4th Street, Box 274 NY 10011 664 n, Director City Department of Health/ Gay & Lesbian Health Ctr. Street, Room 604 NY 10013 995 Ss S 3th Street a, PA 19107 155 5 Stoffer, Executive Director ladelphia AIDS Task Force 16 et 1, PA 19107 86 ds Alliance AIDS Resource Center 0712 75219 (214) 528-4233 Curtis Dixo AIDS Found P.O. Box 66 Houston, TX (713) 524-24 ation of Houston, Inc. 973, Suite L155 77006 27 #U,S, GOVERNMENT PRINTING OFF ICE:1987-056-195 U.C. BERKELEY LIBRARIES co0ou40L1lLe