key: cord-0998607-jbnuhwh5
authors: Lee, Elizabeth H.; Ganesan, Kavitha; Khamadi, Samoel A.; Meribe, Stanley C.; Njeru, Dorothy; Adamu, Yakubu; Magala, Fred; Crowell, Trevor A.; Akom, Eniko; Agaba, Patricia; Desai, Priyanka; Hamm, Tiffany; Teyhen, Deydre; Ake, Julie A.; Polyak, Christina S.; Shaffer, Douglas; Sawe, Fredrick; Hickey, Patrick W.
title: Attaining 95-95-95 through Implementation Science: 15 Years of Insights and Best Practices from the Walter Reed Army Institute of Research’s Implementation of the U.S. President’s Emergency Plan for AIDS Relief
date: 2020-11-09
journal: Am J Trop Med Hyg
DOI: 10.4269/ajtmh.20-0541
sha: 1dcd625ae1fbf33fe5b5a9d229b938a664d8a455
doc_id: 998607
cord_uid: jbnuhwh5

The Walter Reed Army Institute of Research (WRAIR) supports more than 350,000 people on lifesaving HIV treatment in Kenya, Nigeria, Tanzania, and Uganda through funding from the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). Here, we review and synthesize the range of impacts WRAIR’s implementation science portfolio has had on PEPFAR service delivery for military and civilian populations since 2003. We also explore how investments in implementation science create institutional synergies within the U.S. Department of Defense, contributing to broad global health engagements and improving health outcomes for populations served. Finally, we discuss WRAIR’s contributions to PEPFAR priorities through use of data to drive and improve programming in real time in the era of HIV epidemic control and public health messaging that includes prevention, the 95-95-95 goals, and comorbidities.

Since HIV/AIDS was first recognized, more than 75 million people have been infected, and 32 million have died worldwide. 1 The Joint UN Programme on HIV/AIDS (UNAIDS) estimates that the number of people living with HIV (PLHIV) has increased from 7.9 million in 1990 to 37.9 million in 2018. Concurrently, annual new infections have declined from a peak of 2.9 million in the late 1990s to 1.7 million in 2018, and HIV-associated deaths have declined over 55% from a peak of 1.7 million in 2003-2004. 2 As the United States' largest foreign aid program, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) uses a whole-of-government approach and has become a model for foreign aid programs through focus on person-centered health impact, fiscal efficiency, and accountability. 3 Since 2003, PEPFAR's leadership in the global HIV response has transformed the previously unchecked pandemic so that control is now in sight. Countries are achieving or nearing the UNAIDS "90-90-90 by 2020" goals: 90% of PLHIV will know their status, 90% of those who know their status will be on treatment, and 90% of those on treatment will be virally suppressed. 4 These achievements necessitated an unprecedented implementation science program to improve scale, pace, and efficiency to achieve even more ambitious goals of 95-95-95 by 2030. 5 Recognizing the threat posed to civilian and military populations, the U.S. Department of Defense (DOD) established the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research (WRAIR) in 1986. 6 Pioneering WRAIR scientists launched a force-wide HIV screening program and developed countermeasures to protect military and civilian populations through education, antiretroviral therapy (ART), and vaccine development. The Walter Reed Army Institute of Research also established an international network of community-based research sites (Supplemental Table 1 ), leading to notable successes such as the RV144 "Thai Trial" that established proof of concept for vaccine efficacy and set the stage for ongoing trials of next-generation candidate vaccines. 7, 8 Since 2004, the WRAIR has implemented PEP-FAR programs among military and civilian communities in Nigeria, Kenya, Tanzania, and Uganda ( Figure 1 ).

In contrast to its partner organization, the DOD HIV/AIDS Prevention Program (DHAPP), which is focused specifically on working with foreign military partners, WRAIR's PEPFAR program is unique in that its scope of work explicitly includes both military and civilian partner institutions and populations. The DOD Global Health Engagement model emphasizes partner military health and readiness, engagement of partner militaries in research and public health activities, and community engagement. 9 Walter Reed Army Institute of Research's PEPFAR programs advance the PEPFAR goal of epidemic control while adhering to the ethical mandates of equipoise and engagement of multiple stakeholders in clinical research related to its mission of developing vaccines and other countermeasures to HIV. The Department of Defense HIV/AIDS Prevention Program implementation science efforts have centered on seroprevalence and behavioral epidemiology risk surveys and prevention interventions specific to military service members and their families. Although DHAPP-led programs are outside the scope of this article, WRAIR PEPFAR programming benefits from these learning models, and uses implementation science that is responsive to the needs of the diverse population of people and communities served. Although WRAIR's PEPFAR portfolio is more narrowly focused from a country count perspective than that of the DHAPP, WRAIR programs work on a large scale with high-burden communities, including key and priority populations, using relevant programmatic and implementation science strategies. These continuously evolving programs address the HIV security challenge by improving biopreparedness in alignment with the 2019 United States' Global Health Security Strategy. 10 The Walter Reed Army Institute of Research implements research and evaluation efforts at its PEPFAR program sites according to the three components of PEPFAR's implementation science framework: monitoring and evaluation, operations research, and impact evaluation, to ensure evidence-informed decision-making for program impact and resource allocation. 11 Implementation science is the study of methods to improve the uptake, implementation, and translation of research findings into routine practices to accelerate progress. 11 Over the past 15 years, the WRAIR has leveraged its research mission and capabilities to implement an implementation science portfolio to improve HIV service delivery for PEPFAR-supported programs. At this important milestone, we review impacts of this portfolio on HIV programs, policy, and science.

We reviewed the WRAIR PEPFAR research portfolio from 2003 to 2019, inclusive of PEPFAR-funded studies and externally funded studies that leverage WRAIR's PEPFAR program sites. We reviewed protocols and publications, and solicited additional information from collaborators and study investigators (Supplemental Tables 2 and 3) .

Over the past 15 years, the WRAIR has undertaken 25 PEPFAR-funded implementation science studies, in addition to multiple externally funded studies leveraging PEPFAR sites (Table 1) . Of these, 12 have completed clinical data collection, whereas the remainder are in development or ongoing. Walter Reed Army Institute of Research's implementation science studies have been designed in response to PEPFAR technical priorities in the areas of HIV prevention (n = 10); first 95 (n = 17), second 95 (n = 15), third 95 (n = 12); and comorbidities (n = 11), with most cross-cutting (n = 19). Using this framing, we synthesize studies of chief importance ( Table 2) . As most people served by WRAIR's PEPFAR program sites are civilians with no military affiliation, its implementation science research reflects broadly applicable PEPFAR priorities and clinical care.

Prevention. Walter Reed Army Institute of Research's prevention studies address PEPFAR's focus on key prevention activities for populations at high risk for HIV acquisition: preexposure prophylaxis (PrEP), voluntary male medical circumcision, empowerment of adolescent girls and young women, and prevention of mother-to-child transmission (PMTCT) of HIV infection. For example, in Uganda, WRAIR and Makerere University Walter Reed Project (MUWRP) routinely work together to improve implementation of prevention services for priority populations through translation of research findings to programmatic improvements. This partnership assessed acceptability, uptake, and adherence to PrEP, as well as retention in care, among adolescent girls and young women who sell sex, a major behavioral driver of incident HIV infection (RV476). 12, 13 Challenges with stigma and gender-based violence due to misunderstanding of PrEP as ART because of similar packaging were noted and addressed through counseling and referral. Poor PrEP adherence through comparison of serum tenofovir levels to pill counts has also informed counseling during PrEP services (unpublished data). Through the determined, resilient, empowered, AIDS-free, mentored, and safe program, WRAIR and MUWRP have linked these girls to a core packet of interventions 

Objective: To evaluate the impact of the current WHO "Test and Start" strategy on the TB care cascade in PEPFAR supported TB-HIV programs. Key findings: TB preventive therapy initiation increased during the "surge" and plateaued during "sustained" phases.

Because of an isoniazid stock-out, a "dip phase" was recorded. There was overall initiation rate of 79%.

(continued) to achieve a substantial reduction in new infections among adolescent girls and young women. The evidence from RV476 has been disseminated to key in-country stakeholders and communicated across various international platforms (Supplemental Table 3 ) to refine PrEP implementation guidelines and further inform PrEP delivery strategies in this key population.

In partnership with the WRAIR, in 2009, MUWRP also instituted the first facility-based voluntary medical male circumcision program in Uganda, followed up by the introduction of a rural community-based mobile clinic in 2011. In collaboration with Boston University, a micro-costing study estimated the cost of improving access to male circumcision in the mobile clinic setting compared with health facilities (RV346). The study found that the mobile clinic program improved access for remote, high-risk, relatively poor populations at a cost of $27-$38 per circumcision through reductions in out of pocket expenditures for travel and lost time at work. 14 Over time, WRAIR's programming in East Africa has led to high uptake of male circumcision in civilian and military programs, which creates a useful backdrop for future studies to occur, potentially reducing incident infections. Walter Reed Army Institute of Research's counterpart DHAPP has also worked extensively with military populations on voluntary medical male circumcision programming and implementation science from the earliest days of this intervention. 15 Walter Reed Army Institute of Research's PEPFAR programs implement PMTCT interventions alongside studies of 

Objective: To evaluate the impact of provision of comprehensive and integrated prevention, treatment, and care at a community-based clinic operated by an organization experienced in providing HIV prevention, care, and support services to key populations. Key findings: Multiple analyses complete or in progress.

Although there was high acceptance of HIV testing and low loss to follow-up among individuals who were already on ART or engaged in treatment as prevention (TasP), a higher than expected proportion did not engage in TasP, suggesting the need for customized treatment preparation and an increase in enabling environments to support HIV treatment access with this key population. 57 

Open-label, randomized intervention

Objective: To determine the effectiveness of the SLATE algorithm in increasing ART initiation, compared with standard care, in nonpregnant adults. Key findings: In South Africa, the SLATE algorithm increased the uptake of ART within 28 days by 10% and showed a numerical increase (6%) in retention at 8 months. In Kenya, the algorithm increased the uptake of ART within 28 days by 6% but found no difference in retention at 8 months. Eightmonth retention was poor in both arms and both countries. These results suggest that a simple structured algorithm for same-day treatment initiation procedures is feasible and can increase and accelerate ART uptake but that early retention on treatment remains problematic. 22 

Title: Impact Evaluation of PEPFAR-funded PMTCT Activities on Infant Mortality in Kenya

Pooled crosssectional

Objective: To evaluate the impact of PEPFAR funding on key PMTCT related health outcomes, including infant mortality, in Kenya and to assess the degree to which the relationship between PEPFAR funding and key PMTCT-related health outcomes is mediated by process indicators collected as part of the routine monitoring and evaluation of PEPFARfunded PMTCT programs. Key findings: Evidence from publicly available data suggests that PEPFAR's PMTCT funding was associated with a reduction in infant mortality and an increase in HIV testing during ANC in Kenya. The full outcome of funding may not be realized until several years after allocation. strategies to identify women living with HIV, and protect uninfected mothers and improve delivery of care. 16 In collaboration with Harvard University, WRAIR and its Kericho site in Kenya helped estimate that 273,924 infant deaths were averted in Kenya between 2004 and 2014 through PEPFAR PMTCT funding, or that a $0.33 increase in per capita PEPFAR PMTCT funding was associated with a 14-16% reduction in infant mortality (RV516). 17 In partnership with Boston University, the WRAIR explored the impact of adding mentor mothers versus standard care alone on maternal and infant outcomes (RV465), and demonstrated that maternal and child health clinics offered a lower cost alternative for initiating pregnant women on ART (RV342). 18 20 The Walter Reed Army Institute of Research routinely evaluates program testing performance across testing modalities at facilities and in communities disaggregated by age-group, gender, and key populations, with special emphasis on adolescents, young adults, and adult men.

HIV surveillance studies help to identify and close the remaining gaps to reach the first 95 in specific populations. In 2015, the WRAIR collaborated with the Kenya Defense Forces to conduct a prevalence assessment of HIV, tuberculosis (TB), and malaria among the Kenyan military population (RV292). This study helped the WRAIR and the Kenyan military to focus testing initiatives on highest risk populations within the forces. Furthermore, findings informed testing modality prioritization and planning for force healthcare needs and contributed to improved case finding in men and the services generally. In Uganda, the WRAIR conducted an integrated behavioral and biological survey, finding a high prevalence of HIV, hepatitis B, and seropositivity for syphilis in remote fishing communities on Koome and Buvuma islands, while linking newly identified participants to treatment (RV432) (unpublished data).

Recently, many countries have undertaken surveillance activities to estimate HIV prevalence, assess progress toward 95-95-95, and inform resource allocation for targeted case finding. 21 Surveillance systems incorporating rapid tests for 

Monitoring and evaluation X X X --8 RV415

Monitoring and evaluation X X X X X 9

RV433

Monitoring and evaluation X X

Monitoring and evaluation --

Monitoring and evaluation -X X -X 23 RV559

Monitoring and evaluation --

Monitoring and evaluation X X X X X Select WRAIR Implementation Science Studies with outside funding that leverage PEPFAR sites 26

RV368 * Exemplary ACTG trials with major findings/publications. recent infection within the past year are supported by the WRAIR and other PEPFAR implementing agencies in Kenya, Nigeria, Tanzania, and Uganda. Data from these studies will inform the incorporation of recency testing into national surveillance activities for early detection of transmitting networks, such as during outbreak investigations. Each of these examples of WRAIR's contribution to surveillance provides critical information for targeting programmatic response in the highest risk populations. The second 95: treatment. Through multiple studies, WRAIR has addressed improvements in care for the second 95, which aims for PLHIV to initiate and adhere to lifelong, uninterrupted ART. In collaboration with Boston University, WRAIR-supported PEPFAR sites in Kericho, Kenya, evaluated an algorithm to determine eligibility for same-day initiation of ART, with an overall goal of reducing patient attrition at point of care (RV494). 22 The trial found persistent barriers to early or same-day ART initiation based on clinical practice, 23 highlighting the need for improved guidance and training for clinical providers. The site also collaborated with the NIH, finding that for PLHIV with severe immunosuppression who initiate ART, baseline low body mass index (BMI) and hemoglobin with high C-reactive protein and D-dimer may be clinically useful predictors of immune reconstitution inflammatory syndrome and death (RV246). 24 One of the largest and longest running protocols under WRAIR's PEPFAR research portfolio with second 95 impacts is The African Cohort Study (AFRICOS). The African Cohort Study examines the drivers of quality HIV clinical care across WRAIR programs in four countries, fosters international and domestic partnerships, enables ongoing evaluation of PEP-FAR performance, and elucidates ART as a chronic care model within resource-constrained settings (RV329). Consistent with changing guidelines for ART initiation, the study has documented a decreased interval between HIV diagnosis and ART initiation from a median of 22 months before 2006 to just 0.5 months after 2016. 25 As millions of PLHIV transition to dolutegravir-based ART, AFRICOS is poised to track healthrelated outcomes including development of comorbid conditions, adverse effects, and drug resistance. In response to growing concern about HIV prevention and treatment in young age-groups, the study has recently been expanded to include participants aged 15-17 years, to inform programs and policies for this critical age-group with historically poor HIVrelated outcomes.

The African Cohort Study has also leveraged data to describe gender-based differences in HIV care and treatment to bridge critical gender-specific gaps. Despite experiencing more social barriers to care, women are diagnosed and engaged in care earlier in their disease process compared with men, partly because of availability of joint women-centric services at HIV clinical facilities such as prenatal and reproductive health services (unpublished). Differentiated models of care delivery are needed to improve engagement of men and optimize support to already-engaged women. In addition, data from AFRICOS have shown that advanced HIV disease at enrollment, defined as CD4 < 200 cells/mm 3 , was more common among participants who were in Tanzania, male, aged > 29 years, highly educated, and with higher WHO clinical stage. Factors associated with a lower risk of advanced disease were > 1 year since HIV diagnosis and being on ART for at least 6 months (unpublished). These results have informed targeting of individual factors in WRAIR-supported PEPFAR programs to address advanced disease when refining care and treatment strategies, especially in the era of test and treat.

The third 95: viral suppression. Attaining viral suppression requires a combination of the right drug regimen, medication adherence, and viral load monitoring, and WRAIR has been at the forefront of this work. In 2010, WRAIR undertook the Clinic-based ART Diagnostic Evaluation randomized, controlled trial in Kenya that demonstrated the feasibility, superiority, and cost-effectiveness of routine viral load versus standard of care monitoring in adults initiating ART at that time in rural, district-level HIV clinics (RV257). 26 The clinic-based ART Diagnostic Evaluation reflected WRAIR's forward posture on optimal patient monitoring, and findings supported global policy updates made shortly thereafter for routine viral load monitoring. 27 The Clinic-based ART Diagnostic Evaluation demonstrated that rigorous trials could be conducted in a routine clinical setting, paving the way for future, generalizable research including the AFRICOS.

Walter Reed Army Institute of Research has also evaluated early signs of population-level drug resistance and assessed viral load and drug resistance patterns in children and adults (Table 1 ). In 2016, WRAIR undertook a retrospective evaluation of early warning indicators of drug resistance in the Southern Highlands of Tanzania (RV433), which improved the capacity of healthcare providers to conduct surveillance for drug resistance and informed the 2019 National Report for Monitoring Development of HIV Drug Resistance. 28 More recently, AFRICOS found both pretreatment and acquired resistance across the four countries of enrollment, the latter suggesting that strategies emphasizing adherence counseling while delaying ART switch may need modification. 29 In collaboration with the Uniformed Services University of the Health Sciences, viral load and drug resistance data from children aged 1-19 years in Tanzania (RV517) and Kenya (RV518) are being used to inform real-time treatment decisions for regimen optimization. Forthcoming results will inform funding and policy decisions.

African Cohort Study findings support a growing body of literature that suggests the accepted viral suppression threshold may need to shift from 1,000 to a more stringent < 200 copies per milliliter (c/mL). African Cohort Study participants with persistent low-level viremia (200-999 c/mL) were more likely to exhibit subsequent virologic failure than those < 200 c/mL. 30 These findings helped inform downward revision of Tanzanian and Kenyan national viral load threshold definitions of undetectable viral load to < 50 c/mL and < 400 c/mL, respectively. 31, 32 The Nigeria program is using this information to enroll clients with persistent, low-level viremia into enhanced adherence counseling with repeat viral load testing to achieve suppression < 200 c/mL. In the era of Undetectable = Untransmittable, viral load threshold policy refinements have the potential to prevent significant transmission of the virus.

Comorbidities. President's Emergency Plan for AIDS Relief strategies for implementing a multipronged approach to HIV epidemic control include prevention and clinical services for HIV-related comorbidities such as TB, sexually transmitted infections, and mental health disorders. In response, WRAIR has incorporated each of these comorbidities into implementation science efforts. For example, the program in Kericho, Kenya, supported the first regional hospital to integrate TB and HIV care in a single clinic in 2005. 33 In addition, WRAIR has conducted several evaluations of TB and TB preventive therapy in Nigeria, which have been critical in direction setting for the Nigerian Ministry of Defence program (RV528 and RV557) and nationally (RV555). Preliminary data have led to expanded GeneXpert laboratory services (Sunnyvale, CA) and collaborations, improved sample referral and operations, and increased uptake of TB preventive therapy among PLHIV in Nigeria.

The African Cohort Study characterizes how HIV comorbidities such as malignancy, cardiovascular events, malnutrition, anemia, and cognitive decline impact clinical outcomes and help define the healthcare needs of an aging African HIV population. Cervical cancer accounts for 25% of female cancers in Africa, with an incidence of 31 per 100,000 women. 34, 35 African Cohort Study data on cervical cancer screening help set PEPFAR program targets and will further elucidate the interplay between HIV, the immune system, and human papillomavirus-induced carcinogenesis. 36 African Cohort Study findings suggest that PLHIV on ART had an increased risk of noncommunicable diseases compared with those not on ART. 37 In addition, AFRICOS is being used to monitor the transition to dolutegravir as firstline treatment, providing real-time data to inform program improvement. Preliminary data show that participants prescribed tenofovir/lamivudine/dolutegravir (TLD) developed a higher BMI than those on other ART regimens (unpublished). Participants who were ART naive had a 55% lower rate of developing high BMI than those on non-TLD ART, and hyperglycemia incidence was increased with exposure to any ART, particularly TLD (unpublished). These findings have policy implications for rollout of dolutegravir, as metabolic adverse event profiles differ between regimens. Comprehensive care will need to address noncommunicable diseases in PLHIV as they survive to older ages. 37 The cohort has also identified mental health as a driver of HIV outcomes, for example, describing depression as a predictor of HIV viral load. 38 Leveraging PEPFAR sites for impact. Walter Reed Army Institute of Research leverages knowledge and skills in PEP-FAR program management, research, and implementation science for translation of research into impact. Walter Reed Army Institute of Research's PEPFAR research portfolio incorporates institutional partnerships and synergies that maximize return on investments. Collaborations with other U.S. government agencies and academic partners such as Boston University, Harvard University, and University of Maryland have leveraged WRAIR's PEPFAR sites and external funding to conduct implementation science work to answer key service delivery questions.

The TRUST study, supported by DOD and NIH funding, used respondent-driven sampling to enroll highly marginalized men who have sex with men and transgender women at PEPFAR sites into HIV programs at community centers in Nigeria (RV368). The study identified an exceptional burden of HIV in Nigerian men who have sex with men, with HIV prevalence more than 50% and incidence more than 15 cases per 100 person-years. 39, 40 The study also identified a substantial need for diagnosis and management of other sexually transmitted infections, and new prevention interventions. [40] [41] [42] [43] [44] [45] [46] [47] Study findings have subsequently been incorporated directly into prevention and clinical service approaches at the community centers.

In Kericho, Kenya, a WRAIR-and PEPFAR-supported clinical care center is co-located with an AIDS Clinical Trials Group clinical research site. Two major publications in The New England Journal of Medicine using data from this site resulted in global policy changes, including shifting standard of care for starting ART while on TB treatment from 6 months to 2 weeks of TB therapy in patients with CD4 < 50 cells/mm 3 (RV249). 48 The site also contributed to the groundbreaking Brief Rifapentine-Isoniazid Evaluation for TB Prevention/ A5279 trial that established the efficacy of a 1-month rifapentine/isoniazid regimen for the prevention of active TB and provided data to guide future TB/HIV program activities (RV367). 49 In 2006, the site collaborated with the NIH in the OCTANE/A5208 study (RV186). This study demonstrated ritonavir-boosted lopinavir plus tenofovir-emtricitabine was superior to nevirapine plus tenofovir-emtricitabine for initial ART in women with prior use of single-dose nevirapine, and that clinical trial adult female participants could successfully be transitioned to local, routine care. 50, 51 The site has further collaborated with the NIH to conduct studies in infants, children, adolescents, and pregnant women to improve HIV treatment and prevention including HIV remission. By implementing collaborations with access to diverse funding streams, WRAIR has created additional opportunities to build upon a strong foundation to translate research into public health impact.

Biopreparedness. President's Emergency Plan for AIDS Relief investments in Africa have helped build a strong foundation for biopreparedness and health security through systems that strengthen local capacity and emphasize effective, efficient, and sustainable health care. 52 These long-term public health and health system strengthening tools have been applied to emerging infectious disease threats, including the 2014 Ebola outbreaks in Nigeria and Uganda and the current COVID-19 pandemic. 53 Walter Reed Army Institute of Research is strongly positioned to rapidly respond to such outbreaks through clinical research and implementation science, in addition to ongoing diagnostic and vaccine development lines of effort. Research skills developed in the conduct of trials and observational studies lay the foundation for public health and countermeasure development across sub-Saharan Africa.

Data for public health impact. Walter Reed Army Institute of Research's program evaluations integrate core performance data streams continuously analyzed across all PEP-FAR programs, with operational and research data collected at the service delivery level to identify program strengths and gaps. For example, Nigerian program direction has been informed by improvements in adolescent viral suppression observed at Nigerian military sites after implementation of a strategy originally piloted in Kenya (RV543). Program evaluations improve staff capacity to critically assess program outputs against the 95-95-95 targets and implement evidenceinformed strategies in response to real-time programming needs. Similarly, AFRICOS data are leveraged to assess PEPFAR priorities, providing real-time feedback to inform program improvement. This includes current priorities such as monitoring the transition to dolutegravir as first-line treatment, the transition to multi-month ART dispensing, viral load suppression and HIV drug resistance, and HIV comorbidities and advanced disease. As PEPFAR countries approach epidemic control, finding cases and maintaining clients on care long-term require increasingly granular data and rapid analysis. Chronic care models will become increasingly important in the care and treatment setting, as will data on HIV coinfections and comorbidities. Longitudinal studies embedded in PEPFAR program sites, such as AFRICOS, present a unique opportunity to characterize these conditions among adolescent and adult populations.

Walter Reed Army Institute of Research's diverse implementation science portfolio has had a significant impact on HIV prevention, 95-95-95, and comorbidity-focused programs, and has informed policies for care delivery across PEPFAR priority areas. Impacts include improved PrEP delivery and PMTCT strategies; results return, linkage, and clinical management; expansion of viral load testing, especially in key and priority populations; and medication adherence through viral load monitoring. In addition, the portfolio addresses the complete spectrum of long-term HIV health, including comorbidities as the population ages.

Nested within the WRAIR enterprise, investments in implementation science provide direct benefit to PEPFAR service delivery for military and civilian populations while creating institutional synergies that contribute broadly to the DOD's global health-oriented research mission. Grounding service delivery in implementation science enables WRAIR to leverage capabilities and partnerships, and enhance quality and sustainability, while securing the PEPFAR priorities of accelerating access to HIV treatment, focusing prevention for maximum effect, and increasing the impact and costeffectiveness of every dollar invested. Over time, WRAIR's PEPFAR program has shortened data collection to inform real-time application of findings to help control the epidemic.

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Acknowledgments: We wish to acknowledge the important contributions of the WRAIR U.S. Medical Research Directorate-Africa, its country directors' oversight of PEPFAR programs, implementation science, and clinical research in Kenya, Nigeria, Tanzania, and Uganda, and the support staff for program and clinical research sites who have made this work possible. 

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