A Multilevel Perspective on PrEP Adherence in HIV Prevention: An Integrative Review Guided by the Socioecological Model

Pre-exposure prophylaxis (PrEP) remains one of the most effective strategies for preventing HIV infection, yet its success depends on sustained adherence. Evidence increasingly shows that adherence lapses are not purely behavioral but stem from interacting biological, psychological, and social factors. This review aimed to synthesize existing evidence on how hazardous alcohol use, post-traumatic stress disorder (PTSD), and gut microbiome dysbiosis interact as syndemic determinants of PrEP adherence, using the Socioecological Model (SEM) to interpret multilevel influences.An integrative review was conducted following Whittemore and Knafl’s (2005) five-stage framework—problem identification, literature search, data evaluation, data analysis, and presentation. Systematic searches were performed in PubMed, PsycINFO, Scopus, and Web of Science for studies published between 2016 and March 2025. Inclusion criteria covered peer-reviewed, English-language human studies linking PrEP adherence with alcohol use, PTSD, or microbiome disruption. Two reviewers independently screened, extracted, and appraised data for methodological rigor and conceptual relevance. Findings were integrated thematically and interpreted across SEM levels.Fifteen studies met inclusion criteria. Hazardous drinking (55–70%) and PTSD (28–43%) were independently associated with reduced adherence, with combined exposure decreasing adherence from >80% to approximately 54–60%. Odds ratios for nonadherence ranged 1.8–3.2. Microbiome dysbiosis, particularly reduced Lactobacillus and elevated inflammatory markers, was linked to gastrointestinal intolerance and discontinuation. Six recurring themes reflected syndemic reinforcement across biological, psychological, and structural domains.Adherence to PrEP is shaped by interconnected mechanisms rather than isolated behaviors. Future longitudinal and mixed-methods studies should evaluate trauma-informed, microbiome-supportive, and nurse-led interventions, grounded in the Socioecological Model, to achieve sustainable and equitable HIV prevention.