Alcohol Misuse, Gut Microbial Dysbiosis and PrEP Care Continuum: Application and Efficacy of SBIRT Intervention - 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.
