key: cord-324034-6cmztvyf
authors: Ashare, Rebecca L; Bernstein, Steven L; Schnoll, Robert; Gross, Robert; Catz, Sheryl L; Cioe, Patricia; Crothers, Kristina; Hitsman, Brian; Marhefka, Stephanie L; McClure, Jennifer B; Pacek, Lauren R; Vidrine, Damon J; Vilardaga, Roger; Kaufman, Annette; Edelman, E Jennifer
title: The United States National Cancer Institute’s Coordinated Research Effort on Tobacco Use as a Major Cause of Morbidity and Mortality among People with HIV
date: 2020-08-17
journal: Nicotine Tob Res
DOI: 10.1093/ntr/ntaa155
sha: 
doc_id: 324034
cord_uid: 6cmztvyf

The use of antiretroviral therapy (ART) for people with HIV (PWH) has improved life expectancy. However, PWH now lose more life-years to tobacco use than to HIV infection. Unfortunately, PWH smoke at higher rates and have more difficulty maintaining abstinence than the general population, compounding their risk for chronic disease. In this Commentary, we describe a United States National Cancer Institute (NCI)-led initiative to address the relative lack of research focused on developing, testing, and implementing smoking cessation interventions for PWH. This initiative supports seven clinical trials designed to systematically test and/or develop and test adaptations of evidence-based smoking cessation interventions for PWH (e.g., combination of behavioral and pharmacological). We summarize each project, including setting/recruitment sites, inclusion/exclusion criteria, interventions being tested, and outcomes. This initiative provides critical opportunities for collaboration and data harmonization across projects. The knowledge gained will inform strategies to assist PWH to promote and maintain abstinence, and ensure that these efforts are adaptable and scalable, thereby addressing one of the major threats to the health of PWH. Reducing smoking behavior may be particularly important during the COVID-19 pandemic given that smokers who become infected with SARS-CoV-2 may be at risk for more severe disease.

A c c e p t e d M a n u s c r i p t

improved life expectancy for PWH, with some showing a life expectancy similar to the general population. 1 This public health achievement has increased the need to address modifiable health risk behaviors, most notably tobacco use. PWH now lose more life-years to tobacco use than to HIV 1 and almost one-quarter of all deaths among PWH on ART is attributed to smoking. 2 Although evidence is still emerging, tobacco use may be predictive of COVID-19 disease progression, 3 making PWH who smoke particularly vulnerable to the current pandemic.

Unfortunately, the prevalence of tobacco use among PWH remains disproportionately higher than the general population. 4, 5 In 2014, the smoking rate among PWH in the United States was estimated to be 34% -two-times greater than the general population (17%). 6 Global prevalence is also high: 27 low-and middle-income countries surveyed in 2015 indicated approximately 24% of PWH smoke. 7 Moreover, smoking cessation rates among PWH are lowest among those with a higher prevalence of health disparities including women, non-Hispanic blacks, those with lower educational attainment, and those living below poverty levels. A c c e p t e d M a n u s c r i p t While most PWH are interested in stopping smoking, 4-6 particularly when cessation treatment is integrated with HIV care, 9 there has been a relative lack of research focused on developing and testing smoking cessation interventions specifically for PWH. 4 Reviews conclude that there are insufficient data to indicate that cessation interventions, which are efficacious in the general population, are similarly efficacious for PWH. 5, 10, 11 For example, while mobile behavioral treatments have demonstrated feasibility among PWH, abstinence rates for these interventions remained low at 3 months (10-12%). 12, 13 Pilot studies of behavioral interventions that incorporated motivational interviewing, contingency management, and strategies to address negative affect 10, 14 have shown promise for PWH, but fully powered trials are lacking.

Most studies that have examined the impact of tobacco treatment medications in PWH have utilized NRT, although a few examined varenicline. 10, 14 Recently, an algorithm-based approach for selecting smoking cessation medication demonstrated feasibility and reduced smoking behavior, but abstinence was not examined. 15 Two randomized placebo-controlled trials conducted among PWH found that varenicline significantly increased quit rates, compared with placebo. 16, 17 However, cessation rates among varenicline-treated participants (28-29%) 16, 17 were lower than the general population (44% 18 ).

The limited available research indicates that behavioral interventions and medications yield moderate effects on cessation, but abstinence rates among PWH are generally lower than in the general population. 5, 11 There is also a lack of robust literature regarding strategies for switching treatments when smokers are not responsive to the initial treatment.

Despite evidence that current treatments are better than no treatment, implementation of evidencebased treatments for smoking cessation among PWH remains low, and recommended treatments are inconsistently provided. 19 Recent data from the Veterans Aging Cohort Study found that PWH were less A c c e p t e d M a n u s c r i p t likely to receive NRT than veterans without HIV. 19 Moreover, less than 4% of PWH use varenicline, and only 20% of HIV clinicians recommend varenicline to their patients who smoke. 9 Digital interventions have taken on greater significance during the COVID-19 pandemic. However, a review of smoking cessation apps revealed that only two were developed for PWH. 20 Thus, there is an urgent need to identify novel and scalable strategies that meet the needs of the patients and setting (i.e., community, clinic), including the need to deliver treatments remotely when face-to-face interactions pose health risks, such as during the COVID-19 pandemic. There is also a need for simultaneous evaluation of the patient, clinician, and community/organizational level factors that may impact intervention delivery. Importantly, the studies will be conducted in diverse geographic locations and will recruit PWH through various sites (e.g., VA hospitals, community HIV clinics, academic medical centers, and social media).

These studies will accumulate a large, diverse population that is more representative of the population of PWH who smoke than any single study could have achieved. In addition to enhancing reach, this will enable consideration of health disparities by racial/ethnic groups, socioeconomic status, gender, and sexual orientation. The sum of knowledge obtained from cross-project measures will also facilitate evaluation of effective interventions (vs control) and critically, which aspects are most valuable (e.g., pharmacotherapy vs behavioral; in-person vs remote; clinical vs community vs remote samples). Lastly, another NCI-led FOA on Tobacco Use and HIV in Low-and Middle-Income Countries (https://grants.nih.gov/grants/guide/pa-files/par-18-023.html, https://grants.nih.gov/grants/guide/pafiles/PAR-18-022.html) will allow investigators to link parallel on-going and future research in geographic areas where HIV and tobacco use are major threats.

Because of the success of HIV treatment, we are faced with the need to address the major threat of tobacco dependence to the health of PWH. By supporting the rigorous evaluation of the adaptation and implementation of evidence-based treatments for PWH who smoke, this NCI-led initiative will provide critical knowledge about how to promote abstinence and ensure that these efforts are scalable. These NCI-supported studies will provide an opportunity to disseminate findings to key stakeholders to A c c e p t e d M a n u s c r i p t enhance reach and sustainability, thereby expanding the impact of the NIH's investment. Although additional research is needed, tobacco use likely exacerbates the effects of COVID-19 infection. 3 Physical distancing recommendations have made identifying creative strategies for delivering smoking cessation interventions without face-to-face interactions a priority. The current studies are well-positioned to provide critical information about the impact of COVID-19 on PWH who smoke. Stakeholders interested in tobacco cessation should be aware of this initiative and the rich evidence-base it will provide.

Smoking and life expectancy among HIV-infected individuals on antiretroviral therapy in Europe and North America

Smoking-related health risks among persons with HIV in the Strategies for Management of Antiretroviral Therapy clinical trial

Impact of smoking status on disease severity and mortality of hospitalized patients with COVID-19 infection: a systematic review and meta-analysis

A Review of the Literature Concerning HIV and Cigarette Smoking: Morbidity and Mortality, Associations with Individual-and Social-Level Characteristics, and Smoking Cessation Efforts

Tobacco Use, Use Disorders, and Smoking Cessation Interventions in Persons Living With HIV. Curr HIV/AIDS Rep

Trends in cigarette smoking among adults with HIV compared with the general adult population, United States -2009-2014

Tobacco use among people living with HIV: analysis of data from Demographic and Health Surveys from 28 low-income and middle-income countries. The Lancet Global health

The Impact of Cigarette Smoking on HIV/AIDS: Urgent Need for Research and Cessation Treatment

Positive smoking cessation-related interactions with HIV care providers increase the likelihood of interest in cessation among HIV-positive cigarette smokers. AIDS Care

Smoking Cessation for People Living With HIV/AIDS: A Literature Review and Synthesis

Behavioral Interventions for Tobacco Use in HIV-Infected Smokers: A Meta-Analysis

Long-term Outcomes of a Cell Phone-Delivered Intervention for Smokers Living With HIV/AIDS

A qualitative systematic review of cigarette smoking cessation interventions for persons living with HIV

Delivery and implementation of an algorithm for smoking cessation treatment for people living with HIV and AIDS. AIDS Care

Placebo-controlled randomized clinical trial testing the efficacy and safety of varenicline for smokers with HIV. Drug Alcohol Depend

Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial

Receipt and predictors of smoking cessation pharmacotherapy among veterans with and without HIV

Mobile Applications for the Treatment of Tobacco Use and Dependence

Harmonizing Cigar Survey Data Across Tobacco Centers of Regulatory Science, Center for Tobacco Products, and Population Assessment of Tobacco and Health Studies: The Cigar Collaborative Research Group

A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t