Specific Effects of Integrase Inhibitors on Gut Microbiota in Men Who Have Sex with Men with and without HIV

BackgroundHIV infection and antiretroviral therapy (ART) influence gut microbiota, affecting inflammation, immune function, and systemic health. However, isolating the effects of integrase strand transfer inhibitor (INSTI)-based ART on gut microbiota is complicated by confounding factors, including HIV status, immunosuppression, and sexual behavior. MethodsThis study examined three cohorts of men who have sex with men (MSM): 1) HIV-negative individuals using post-exposure prophylaxis (PEP) (n=22), 2) PWH with <350 CD4 cells/L before and after ART (n=21 and n=13, respectively), 3) PWH on long-term INSTI-based ART with >500 CD4 cells/L (n=17). Fecal microbiota was analyzed through 16S rRNA sequencing, with functional profiling using PICRUSt2. To compare differences in bacterial abundance and functions, we used ANCOM-BC2. ResultsPWH showed significantly lower alpha diversity than HIV-negative participants, especially those with marked immunosuppression. Short-term ART in PEP users showed no significant impact microbiota, while beta diversity clustered by HIV status rather than ART exposure. Pro-inflammatory taxa, such as Prevotellaceae, were enriched in PWH, reflecting interactions between HIV and MSM status. Functional profiling indicated elevated genes linked to antibiotic resistance, metabolism, and stress in PWH. While INSTI-based ART caused minor functional changes, it increased beneficial genera like Barnesiella. ConclusionsWhile HIV significantly disrupts gut microbiota, INSTI-based ART preserves microbial diversity and community structure. Complementary microbiota-targeted interventions could enhance health outcomes for PWH.