The scientific premise behind Project Adhere rests on a well-documented paradox. Oral PrEP, typically a combination of emtricitabine and tenofovir disoproxil fumarate, reduces the risk of HIV acquisition by more than 90 percent when taken as prescribed, a finding established in landmark trials such as iPrEx and PROUD. Yet the protective effect of the drug is exquisitely sensitive to adherence. Pharmacologic studies measuring intracellular tenofovir-diphosphate in dried blood spots have shown that protection drops steeply when fewer than four doses per week are taken. Black men who have sex with men, the very group facing the highest incidence of new infections, have repeatedly been shown in prior research to be less likely to initiate, adhere to, and persist on oral PrEP compared with their white counterparts.

To understand what drives this gap, the research team, led by Darren L. Whitfield of the University of Maryland School of Social Work together with colleagues at Emory University, New Mexico State University, and Vanderbilt University Medical Center, designed an observational study that tracked both behavior and psychology over time. Participants were recruited from Ending the HIV Epidemic jurisdictions, geographic areas selected by federal health agencies because they account for a majority of new HIV diagnoses in the United States. By concentrating on these hotspots, the investigators aimed to study adherence in the settings where improvements would have the greatest public health impact.

The methodological design of Project Adhere reflects a growing recognition that self-reported adherence is unreliable. Previous studies comparing self-report with pharmacologic measures have found that participants frequently overestimate the doses they take, a pattern documented among young men who have sex with men in both clinical trials and community settings. To counter this bias, Project Adhere monitored participants’ PrEP use objectively over the six-month follow-up period while simultaneously administering validated psychometric instruments. These included the Patient Health Questionnaire for depression, the Alcohol Use Disorders Identification Test for alcohol consumption, the Drug Abuse Screening Test for other substance use, and the Brief Resilience Scale for the capacity to recover from stress.

The headline finding of the study is that substance use was significantly associated with lower PrEP adherence. This result aligns with a systematic review published in AIDS and Behavior in 2023, which synthesized evidence from studies enrolling men who have sex with men and transgender women and found consistent links between substance use and diminished adherence to HIV pre-exposure prophylaxis. It also echoes earlier findings from the HPTN 073 trial, in which self-reported substance use behaviors among Black men who have sex with men were associated with both PrEP acceptance and adherence outcomes. The consistency of this association across independent cohorts strengthens the case that substance use is not a peripheral issue but a central mechanism undermining chemoprophylaxis in this population.

The mechanisms linking substance use to missed doses are plausibly multifactorial. Alcohol and drug use can disrupt daily routines that anchor medication-taking habits, impair memory and executive function during intoxication, and increase the perceived burden of a daily pill. Qualitative work with PrEP-prescribed gay and bisexual men has documented that participants themselves perceive alcohol consumption and substance use as direct obstacles to consistent adherence, sometimes describing complete lapses in their medication routines during periods of heavy use. There is also the phenomenon of interactive toxicity beliefs, the concern that combining PrEP with alcohol or drugs could harm the body, which prior research has linked to stigma, substance use, and reduced PrEP uptake.

What makes the Project Adhere findings notable is that substance use emerged as the significant correlate while other psychosocial factors did not reach statistical significance in this sample. Depression, anxiety, stigma, resilience, and self-efficacy have all been implicated in prior literature as barriers or facilitators of PrEP adherence. A syndemic perspective, which holds that clustered psychosocial epidemics such as depression, substance use, and violence exposure interact synergistically to elevate HIV risk, has been widely applied to young Black gay and bisexual men. The Project Adhere results do not invalidate this framework, but they do suggest that within a six-month observational window in this cohort, substance use was the factor with the clearest measurable signal, and that the effects of other psychosocial and structural variables require further study with larger samples.

The study’s limitations are important for calibrating interpretation. With 69 participants, the sample size constrains statistical power, meaning that modest but real associations between other psychosocial factors and adherence may have gone undetected. Observational designs cannot establish causation; it is possible that unmeasured confounders influence both substance use and adherence. Nevertheless, the authors argue that the findings point toward a practical intervention target. Screening for substance use in PrEP clinics serving Black men who have sex with men, and integrating substance use support into HIV prevention services, could address a modifiable behavior that directly compromises the pharmacologic protection the medication is meant to provide.

The structural context surrounding these individual-level findings cannot be ignored. Black men who have sex with men navigate layered stigma related to race, sexuality, and PrEP use itself, along with medical mistrust rooted in historical and contemporary discrimination. Studies in Jackson, Mississippi and Boston documented how stigma, mistrust, and perceived racism suppress PrEP awareness and uptake. Research in Harlem and Atlanta has shown high discontinuation rates even among those who initiate the regimen. Structural racism and racial trauma have been proposed as upstream determinants that shape both mental health burdens and engagement with prevention services. Within this landscape, a daily pill demands a stability of routine, trust, and access that structural inequities actively erode.

The federal Ending the HIV Epidemic initiative has set the goal of reducing new infections by at least 90 percent by 2030, and mathematical modeling suggests that PrEP could substantially reduce incidence among Black sexual minority men if coverage and adherence were equitable. Population-based analyses of the first decade of PrEP use in the United States, however, have documented persistent disparities in uptake by race and ethnicity, with Black men who have sex with men remaining underrepresented among PrEP users relative to their share of new infections. Project Adhere adds a granular, longitudinal, and methodologically careful data point to this national picture, indicating that closing the gap will require more than expanding prescriptions. It will require interventions that meet Black men where the evidence now points: at the intersection of substance use, daily routine, and the social conditions that shape both. The authors call for further research to determine the full impacts of psychosocial and structural factors on adherence and persistence, and for interventions designed to assess and assist Black men who use substances, so that the promise of PrEP can finally be delivered equitably to the communities that need it most.

Subject of Research: Psychosocial and structural factors influencing PrEP adherence among Black men who have sex with men

Article Title: Associations Between Psychosocial Factors and Pre-exposure Prophylaxis (PrEP) Adherence Among Black Men Who Have Sex with Men in Ending the HIV Epidemic Jurisdictions: Findings from Project Adhere

Article References: Whitfield, D. L., Caldwell, J., Edwards, O. W., Mammadli, T., Chandler, C. J., Sullivan, P., & Jones, J. (2026). Associations Between Psychosocial Factors and Pre-exposure Prophylaxis (PrEP) Adherence Among Black Men Who Have Sex with Men in Ending the HIV Epidemic Jurisdictions: Findings from Project Adhere. Archives of Sexual Behavior. https://doi.org/10.1007/s10508-026-03433-1

Image Credits: AI Generated

DOI: 10.1007/s10508-026-03433-1

Keywords: PrEP, HIV prevention, Black men who have sex with men, medication adherence, substance use, Ending the HIV Epidemic, psychosocial factors, health disparities, Archives of Sexual Behavior, Project Adhere, Associations, Between