In 2018, black men who have sex with men (black MSM) accounted for the largest proportion of new HIV diagnosis (38%) relative to Hispanic (30%) or white (25%) MSM in the United States.1 Tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide combined with emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) is efficacious in preventing acquisition of HIV among at-risk MSM and transgender women.2–4 The efficacy of PrEP depends on maintaining protective levels of adherence.5,6 Substance use, particularly stimulant and alcohol use, is common among some MSM,7–10 and is associated with HIV sexual transmission behaviors10,11 and HIV acquisition.12 Therefore, MSM who use substances could benefit from PrEP, but decreased adherence presents a concern.13–15 Moreover, the relationship between substance use and PrEP adherence remains unclear.
In the iPrEx open-label extension study, participants who used stimulants had a 5-fold greater odds of suboptimal PrEP adherence compared to nonusers, but no association with binge drinking was found.16 In other studies, stimulant and alcohol use decreased PrEP adherence.17,18 Some studies have not found significant differences in PrEP adherence among MSM who use alcohol and marijuana.9,15,19,20 At week 4 of a recent longitudinal study of MSM, participants who used stimulants and who reported condomless anal intercourse (CAI) with multiple partners had significantly decreased PrEP adherence, but over the 48-week follow-up period, PrEP adherence increased.8
Thus, the relationship between substance use and PrEP adherence seems complex, and consideration of both the substance used (eg, alcohol vs. stimulants) and the context of use (eg, before/during CAI) is warranted. Although substance use, particularly stimulant use, before/during sex has been shown to confer an increased risk of HIV acquisition,21 to date, this has not been fully examined regarding PrEP adherence.8,15–20 In addition, most studies have not specifically assessed PrEP adherence among Black MSM, although they have significantly lower adherence to PrEP than their white counterparts.15,22,23 Therefore, the objective of this analysis was to determine whether substance use behaviors, including substance use before/during CAI are associated with PrEP initiation and biologically confirmed PrEP adherence among a multicity sample of black MSM in the United States.
Data for this analysis come from the HPTN 073 study. Detailed description of study procedures for HPTN 073 is published elsewhere.20,24 Briefly, HPTN 073 enrolled 226 HIV-negative black MSM between August 2013 and September 2014 in 3 US cities: Los Angeles, California; Washington DC; and Chapel Hill, North Carolina. Eligibility criteria included: 18+ years of age, African American/black (men who were African, Afro-Caribbean, Afro-Latino, or other also eligible), assigned male sex at birth, HIV-negative, and self-report of at least one of the following: CAI with a male partner, anal intercourse with more than 3 male partners, exchanging any anal sex with a male partner for money, gifts, shelter, or drugs, anal sex with a male partner while using drugs or alcohol or being diagnosed with a sexually transmitted infection, and having a male sex partner in the past 6 months. After the baseline visit, study visits occurred at weeks 4, 8, and 13 and quarterly thereafter for up to 52 weeks. Institutional review boards at the respective study sites approved the study.
Outcomes: PrEP Initiation and Adherence
Participants were offered and could initiate PrEP at any time during the study from enrollment to 48 weeks. We defined PrEP initiation as the self-reported date the participant took the first dose.
Adherence was determined by pharmacological testing of 2 types of participant specimens: plasma and peripheral blood mononuclear cells (PBMCs). The levels of tenofovir (TFV) and FTC in plasma and FTC triphosphate and TFV diphosphate in lysed PBMCs were assessed at week 26 and week 52 (midpoint and end of the study, respectively).2 PrEP adherence was defined as those who met the 90% sensitivity threshold for ≥4 doses of FTC/tenofovir disoproxil fumarate per week—consistent with protective levels in the iPrEx study6—from any of the 2 samples types (plasma and PBMC) related to measurements of ≥4.2 ng/mL for TFV and ≥4.6 ng/mL for FTC in plasma and 9.9 fmol/106 for TFV diphosphate and 0.4 fmol/106 for FTC triphosphate in PBMCs.25
Substance Use Behaviors
At baseline and each follow-up study visit, participants self-reported their frequency of alcohol, marijuana, inhaled nitrates (poppers), cocaine (crack and powder), and methamphetamine use in the past 3 months. In addition, for each substance used, participants self-reported whether use occurred within 2 hours before/during CAI. Because of small counts in some frequency categories, we operationalized each substance use in 2 ways: any substance use and substance use before/during CAI (yes/no).
Participants completed questions asking about study site, age, and educational attainment. Incarceration was defined as having ever spent ≥1 night in a jail, detention facility, or prison. Depression symptoms was measured using the brief version of the Center for Epidemiologic Depression scale, with a cutoff score of 10 or more was used to categorize participants as having significant levels of depressive symptoms.26Relationship items included currently in a relationship with a primary/main male partner. Sexual behavior variable included CAI with a HIV-positive/unknown casual male partner in the past 3 months. Baseline sexually transmitted infection diagnosis was defined as any diagnosis of syphilis, Chlamydia trachomatis, and Neisseria gonorrheae at the enrollment visit.
We computed frequencies and percentages to describe the sociodemographic and substance use behaviors of the overall sample, stratified by PrEP initiation. The primary independent variables were any substance use and use of these substances before/during CAI. The dependent variables were PrEP initiation and adherence. Baseline substance use behaviors were used to evaluate associations with PrEP initiation by week 26 (for those who had initiated PrEP) using logistic regression models. We used substance use behaviors at weeks 26 and 52 to evaluate associations with PrEP adherence at the same visits, using logistic regression models. These models were performed using generalized estimating equations,27 across 323 person-visits and specifying a compound symmetry correlation structure. Missing data ranged from 7% (for marijuana and stimulant use before/during CAI variables) to 8% (for alcohol and popper use before/during CAI variables). We used listwise deletion to handle missing data. We conducted all analyses with SAS version 9.4 (SAS Institute, Inc., Cary, NC).
The sample included 226 black MSM, the majority of whom were 25 years of age or older (60%), 25% had a high school diploma or less, 48% reported less than $20,000 in annual income, and nearly a third (31%) reported a history of incarceration (Table 1).
Substance Use Behaviors and PrEP Initiation
Sixty-eight percent of the total sample (n = 153) initiated PrEP at the enrollment visit, with an additional 25 (11%) initiating at a later visit.20 In adjusted models, there was no statistically significant difference in PrEP initiation between participants self-reporting any substance use, including substance use before/during CAI compared to nonuse (Table 2).
Substance Use Behaviors and PrEP Adherence
Of the 178 participants who initiated PrEP, a blood sample for measurement of PrEP adherence was not available for 16 participants at week 26 and 17 participants at week 52, resulting in 323 visits with measured PrEP adherence available for analysis. Overall, of the men who initiated PrEP, 35% (64 of 178) and 36% (54 of 178) had levels consistent with protective levels at week 26 and at week 52, respectively. Furthermore, 25% (n = 44) had levels consistent with protective levels at both study visits. In adjusted models, we found no statistically significant difference in PrEP adherence self-reported marijuana, popper, alcohol, and stimulant use compared to nonuse. Similarly, there was no statistically significant difference in PrEP adherence in self-reported marijuana, popper, and alcohol use before/during CAI compared to nonuse (Table 2). However, participants who self-reported stimulant use before/during CAI compared to those who did not demonstrated a statistically significant lower odds of PrEP adherence (adjusted odds ratio = 0.21, 95% confidence interval = 0.07 to 0.62; P = <0.01; Table 2). This finding was consistent when data were analyzed separately by visit (data included in Supplemental Material, Supplemental Digital Content, https://links.lww.com/QAI/B484). We then performed additional analysis to understand correlates of stimulant use before/during CAI. Among all factors that we assessed, only a history of incarceration was significantly and positively associated with stimulant use before/during CAI (odds ratio = 19.0, 95% confidence interval: 4.7 to 83.0; P = <0.001).
In this analysis of black MSM across 3 US cities in a PrEP demonstration project, most substance use behaviors were not significantly associated with decreased odds of initiation of PrEP or protective levels of PrEP adherence. However, we found that stimulant use before/during CAI was associated with decreased adherence to PrEP.
Our finding that black MSM who engaged in stimulant use before/during CAI had decreased adherence to PrEP is novel. Our finding contrasts with that from O'Halloran et al28 (2019), who did not find a statistically significant association between chemsex and self-reported PrEP adherence. Their study finding is different from ours because it was conducted among predominantly white MSM in England, PrEP adherence was self-reported, and their definition of chemsex included use of crystal meth, gamma-hydroxybutyric acid/GHB, or mephedrone use immediately before, or during sex. Our finding suggests that black MSM who engage in stimulant use before/during CAI may comprise a unique group that could benefit from tailored prevention support regarding PrEP adherence. In post hoc analysis, only previous incarceration history emerged as a significant predictor of stimulant use before/during CAI. This finding is particularly relevant for black MSM, who have disproportionately higher rates of incarceration than their white counterparts.29,30 An incarceration history can disrupt an individual's social and sexual network,31 and exacerbate access to social determinants of health (eg, employment and housing) linked to HIV risk behaviors32,33 and reduced medication adherence.34 Because this finding was observed from post hoc analysis, caution is needed in its interpretation, but certainly, additional investigations to understand the unique characteristics of black MSM who engage in stimulant use before/during CAI is warranted. Alternatively, the relationship between black MSM who use stimulants before/during CAI and lower PrEP adherence may be mediated by severity of stimulant use35 and PrEP-related stigma (ie, rejection based on perception that PrEP use is suggestive of promiscuity or that they were HIV-positive),36–39 which also warrants further investigation.
Findings showing that general substance use did not decrease PrEP adherence are consistent with findings from prior studies.5,15,22,40,41 In addition, the current analysis further expands the literature by showing that alcohol, marijuana, and popper use before/during CAI did not decrease PrEP adherence. These findings underscore that Black MSM who use these substances and who are candidates for PrEP can achieve protective levels of PrEP adherence.
Our analysis had some limitations. The sample was relatively small, especially for conducting separate analysis for some substance use type (ie, crack/cocaine and methamphetamine). Relatedly, the multivariable models were adjusted for a limited set of covariates. We used PrEP adherence data from only 2 time-points. The sexual and substance use behavior data were collected through self-report. We did not assess frequency or route of use (eg, injection vs. oral) of substances used. Generalizability of our findings to the broader community of black MSM in the United States is limited because our sample was recruited from just 3 cities in the United States.
Among black MSM in this study, alcohol, marijuana, and popper use did not decrease initiation of or adherence to PrEP. Thus, black MSM who use these substances, and are candidates for PrEP, can attain protective levels of PrEP adherence, which should increase physician willingness to prescribe PrEP to this group. However, black MSM self-reporting stimulant use before/during CAI had decreased PrEP adherence. Preliminary findings suggest that indicators of structural determinants of health, such as incarceration history, were associated with using stimulant use before/during CAI and present a barrier to attaining the goal of ending HIV in the United States. The findings also suggest that enhanced behavioral health and social services to support MSM who use stimulants before/during CAI are warranted to ensure that they will optimally benefit from PrEP.
The authors thank the study team and participants at the following research sites: University of North Carolina at Chapel Hill (UNC) (CTU: AI069423‐08/CTSA: 1UL1TR001111); George Washington University, Milken Institute School of Public Health (5UM1AI069053); and University of California Los Angeles (UCLA). The authors also acknowledge support from the HPTN Leadership and Operations Center (LOC), FHI 360; HPTN Laboratory Center Quality Assurance, Johns Hopkins University; HPTN Laboratory Center Pharmacology, Johns Hopkins University; HPTN Statistical and Data Management Center, Statistical Center for HIV/AIDS Research and Prevention (SCHARP); and Division of AIDS (DAIDS) at the US National Institutes of Health (NIH); Gilead Sciences, Inc.: Staci Bush, Lindsey Smith, James Rooney, Brenda Ng. Other HPTN 073 Contributors include: Black Gay Research Group, HPTN Black Caucus, and District of Columbia Center for AIDS Research, an NIH-funded program (AI117970).
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