Neuroinflammatory and Syndemic Pathways in HIV Prep Adherence: A Systematic Review

Abstract

Background: Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV, yet adherence remains suboptimal. Alcohol misuse, post-traumatic stress disorder (PTSD), and gastrointestinal (GI) dysbiosis have been proposed as overlapping barriers. This systematic review aimed to evaluate how these factors independently and interactively affect PrEP adherence among HIV-negative populations in the United States.
Methodology: A systematic search was conducted in PubMed, PsycINFO, Scopus, and Web of Science for studies published between 2016 and March 2025 on PrEP adherence, alcohol use, PTSD, and the gut microbiome. Eligible studies included peer-reviewed human research in English that examined PrEP adherence in relation to at least one of these factors, while non-human and non-US studies were excluded. Two reviewers independently screened and extracted data, with disagreements resolved by consensus. Data were analyzed descriptively in R version 4.3.1, and findings were synthesized narratively due to heterogeneity across studies.
Results: Fifteen studies met the inclusion criteria. Hazardous alcohol use was associated with a 55–60% increase in GI complaints, and adherence rates reduced to 54–60%, versus >80% in non-drinkers. PTSD prevalence among PrEP users ranged from 28–43%, with severity 40–50% higher among alcohol users; trauma-related avoidance and cognitive impairment were key drivers of missed doses. Microbiome analyses suggested reduced Lactobacillus/Bifidobacterium and elevated Enterobacteriaceae were associated with reported intolerance and discontinuation. Structural inequities, stigma, and racial disparities further compounded nonadherence, particularly among Black and Latinx MSM.
Conclusions: Alcohol misuse, PTSD, and GI dysbiosis appear to interact as a syndemic that may undermine PrEP adherence. Addressing these barriers requires integrated, trauma-informed, and microbiome-sensitive interventions to improve HIV prevention outcomes.