Pre-exposure prophylaxis (PrEP), a medication regimen to reduce HIV transmission risk among HIV negative
individuals, has utility in helping to reach national HIV prevention goals. However, clinical side effects,
particularly those impacting gastrointestinal (GI) (nausea, vomiting, loss of appetite), hepatic and renal injury
outcomes may inhibit PrEP persistence. Importantly, alcohol use which is frequent in PrEP users may interact
with PrEP and exacerbate PrEP-associated adverse GI effects and consequently affect PrEP persistence.
Recent data implicates that these side effects are likely associated with changes in the gut microbiome
(dysbiosis). Despite the important ramifications that PrEP, alcohol, and their combined use may have on the
gut dysbiosis and subsequent PrEP continuance, there is little research to elucidate this interaction and few
attempts to address it. Moreover, there is little research exploring decision-making processes regarding alcohol
and PrEP utilization and adherence among PrEP users. To address these gaps in research, this study will
employ the following aims. Aim 1: Qualitatively explore mechanisms by which alcohol use impacts
movement through the PrEP continuum and understand how an early intervention and treatment
approach impacts alcohol use and PrEP adherence. Aim 2: Investigate the effectiveness of the SBIRT
intervention in preventing hazardous alcohol use and its impact on gut dysbiosis in PrEP users. Within
this longitudinal cohort study, we will identify alcohol impacted participants, with patterns of use
ranging from episodic to long-term (engaging in risky or hazardous use). Aim 3: To determine
alterations in the gut microbiome (dysbiosis), intestinal homeostasis, systemic inflammation, and
markers of liver disease associated with hazardous alcohol use among PrEP users. Recruiting from local
PrEP clinics, we will determine alterations in the gut microbiome, intestinal homeostasis, systemic inflammation
and markers of liver disease associated with alcohol and PrEP use. We will also execute a randomized control
trial among PrEP users demonstrating heightened alcohol use to test the effectiveness of the Screening, Brief
Intervention, & Referral to Treatment (SBIRT) intervention to reduce alcohol use and examine subsequent
impact on the gut microbiome compared to individuals receiving treatment as usual and PrEP users not
demonstrating elevated alcohol use. Finally, we will employ qualitative methods (in-depth interviews) and
analysis to understand decision-making factors influencing PrEP adherence and alcohol use over time. Priority
populations, including those engaging in alcohol use, need to increase engagement in the PrEP Care
Continuum to optimize HIV prevention. Clinical research has yet to focus on interactions between PrEP,
alcohol use and GI adverse events. This study may have important implications for mitigating a salient
challenge to PrEP adherence and persistence (side-effects) and elucidating, from clinical and public
health standpoints, factors promoting maintenance in the PrEP care continuum.
