The current study was designed to develop a better understanding of the nature of the relationships between mental health burden, drug use, and unprotected sexual behavior within a sample of emerging adult gay and bisexual men, ages 18–19 (N = 598) and to test a theory of syndemics using structural equation modeling. Participants were actively recruited from community-based settings and the Internet for participation in a seven-wave cohort study. Data for participant characteristics and mental health were collected via computer-assisted survey, while drug use and unprotected sex behaviors for the month prior to assessment were collected via a calendar-based technique. Using the baseline data, we developed and tested structural equation models for mental health burden, drug use, and unprotected sex and also tested a second-order model for a single syndemic. First-order measurement models for each of the three epidemics were successfully identified using observed data. Tests of a second-order model seeking to explain the three epidemics as a single syndemic fit poorly. However, a second-order construct comprised of mental health burden and drug use fit the data well and was highly associated with the first-order construct of unprotected sex. The findings advance a theory of syndemics and suggest that in order to be maximally effective both HIV prevention and HIV care must be delivered holistically such that sexual risk behaviors are addressed in relation to, and in sync with, the drug use and mental health of the individual.

The antiretroviral drug combination emtricitabine and tenofovir disoproxil fumerate (TDF/FTC) taken as preexposure prophylaxis (PrEP) is effective in preventing HIV infection, yet it also requires adherence and potentially decreases condom use. This study sought to examine these issues among a key population at risk for HIV, substance-using men who have sex with men (MSM). We conducted semi-structured interviews with an ethnically diverse sample of 30 young (aged 20–35) MSM prescribed PrEP within a large integrated healthcare system in San Francisco, who had reported recent drug use or hazardous drinking and one or more missed doses of PrEP. We explored participants’ risk perception and sexual risk behavior, drug and alcohol use, and PrEP adherence in the context of substance use. Interviews were transcribed and coded using a directed content analysis approach to identify key categories and commonalities, and differences across participants. Salient sub-categories included positive psychological effects of being on PrEP (e.g., decreased anxiety, feelings of empowerment), social effects (e.g., reduced HIV stigma), and reduction in overall perceptions of HIV risk. While overall reported use of condoms went down and many reported a brief period of increased condomless sex following PrEP initiation, others continued condom use with most of their sexual partners. Contextual factors influencing their decision to engage in condomless sex included how well they knew the partner and whether the partner was on PrEP or HIV antiretroviral treatment. Factors associated with poor adherence included disruptions in daily routine and use of alcohol and methamphetamine. PrEP-prescribing clinicians should support their patients in making informed decisions about condom use and identifying strategies to maximize adherence in the context of substance use.

Black and Hispanic/Latinx transgender women in the United States (U.S.) are disproportionately affected by HIV. Preexposure prophylaxis (PrEP) reduces risk of HIV infection but PrEP uptake remains low among Black and Hispanic/Latinx transgender women. Between July 2018 and August 2019, we conducted individual interviews with 30 Black and Hispanic/ Latinx transgender women who were prescribed PrEP through a PrEP demonstration project and 10 healthcare providers who provide PrEP services to transgender women in Los Angeles and San Diego, California. The interviews assessed general attitudes, experiences, and beliefs about PrEP as well as individual-, interpersonal-, community-, and structural-level barriers to PrEP uptake and adherence. PrEP adherence was assessed by collecting quantitative intracellular tenofovir-diphosphate (TFV-DP) levels in retrospect on batched, banked dried blood spot (DBS) samples. We utilized qualitative content analysis to identify themes from the interviews. Findings indicated the presence of individual-level barriers including cost concerns, mental health issues, substance use, and concerns about PrEP side effects including hormone interaction. Interpersonal-level barriers included the influence of intimate/romantic partners and the impact of patient-provider communication. Communitylevel barriers consisted of experiencing stigma and negative community opinions about PrEP use as well as having negative experiences in healthcare settings. Structural-level barriers included unreliable transportation, employment, and housing insecurity. Interventions aiming to increase PrEP uptake and adherence among Black and Hispanic/Latinx transgender women in the U.S. should employ a multilevel approach to addressing the needs of transgender women, especially the structural barriers that have greatly limited the use of PrEP.