Alcohol-Induced Microbial Dysbiosis and Psychosocial Stressors Undermining PrEP Adherence: A Mixed Methods Analysis in HIV-Negative African American Adults

HIV remains a major public health challenge in the Southern United States, with African American communities facing elevated risk. This study investigates how hazardous alcohol use, psychological distress, and gut microbial dysbiosis affect PrEP adherence and evaluates a trauma-informed SBIRT intervention to improve outcomes. This 12-month convergent mixed-methods study was conducted through Kentucky State University with two collaborating clinics. Seventy-eight HIV-negative African American adults on PrEP were recruited via referrals and community outreach and randomized to SBIRT (n = 30), Treatment-as-Usual (n = 30), or a non-hazardous drinking reference group (n = 18). Quantitative data included surveys (AUDIT, PHQ-9, PCL-5), pharmacy refill logs, and stool-based 16S rRNA sequencing. The qualitative arm applied a phenomenological approach with 40 purposively selected participants completing semi-structured interviews at baseline, 3, 6, and 12 months. Interviews were thematically coded in Dedoose and integrated with quantitative analyses (chi-square, ANOVA, Pearson correlations, logistic regression) to examine clinical outcomes and lived experiences influencing PrEP adherence. Among 78 participants, multivariate logistic regression identified hazardous alcohol use (OR=2.9, p=0.008), PTSD (OR=3.6, p=0.003), depression (OR=2.7, p=0.029), and microbial dysbiosis (OR=3.3, p=0.006) as predictors of PrEP non-adherence (<85%). Compared with TAU, SBIRT participants showed higher adherence (80% vs. 53%, p=0.014), greater microbial diversity (Shannon Index 2.6 vs. 1.9, p=0.004), and lower inflammatory biomarkers (IL-6, TNF-α, both p<0.05). They also reported fewer depressive (PHQ-9: 7.8 vs. 11.5, p=0.004) and PTSD symptoms (PCL-5: 29.1 vs. 35.4, p=0.007), alongside safer sexual behaviors. Qualitative analysis confirmed that stigma, trauma, and gut discomfort disrupted adherence, while SBIRT counseling enhanced self-awareness, reduced emotional fatigue, and supported behavioral change. These findings highlight that PrEP adherence can be enhanced through trauma-informed, culturally grounded support in combination with long-acting formulations and probiotic strategies.