Background The gastrointestinal tract serves as a major viral reservoir in HIV infection, and persistent gut dysbiosis contributes to systemic inflammation and immune dysfunction despite effective antiretroviral therapy (ART). Integrase strand transfer inhibitor (INSTI)–based regimens are now preferred for their efficacy and tolerability; however, their impact on gut microbial restoration remains underexplored. Methods This study analyzed fecal microbiota composition in 30 HIV-positive adults—10 ART-naïve, 7 receiving INSTI-based ART for 2 years, and 13 receiving INSTI-based ART for 2–5 years. 16S rRNA gene sequencing of stool samples (V3–V4 regions) was performed to evaluate bacterial diversity and taxonomic shifts. Microbial composition was compared across groups and correlated with CD4 + T cell counts. Results Alpha diversity showed a non-significant yet progressive increase from ART-naïve to long-term INSTI-treated patients, suggesting partial restoration of microbial diversity. At the phylum level, Firmicutes increased and Bacteroidetes decreased in treated groups, indicating a shift toward eubiosis. Long-term INSTI therapy enriched beneficial taxa such as Faecalibacterium prausnitzii, Lactobacillus ruminis, Eubacterium biforme, and Bifidobacterium longum , while reducing pro-inflammatory Bacteroides fragilis and Haemophilus parainfluenzae . Moreover, higher CD4 + T cell counts showed a positive correlation with the abundance of short-chain fatty acid–producing bacteria and with an increased Firmicutes/Bacteroidetes ratio, indicating improved mucosal integrity and immune homeostasis. Conclusion Integrase inhibitor–based ART promotes partial normalization of gut microbiota composition in HIV-infected patients, enhancing beneficial taxa linked to immune recovery. These findings underscore the potential of microbiota-targeted adjunctive interventions—such as probiotics or dietary modulation—to support mucosal immunity and long-term health in people living with HIV.
Karaca et al. (2026) studied this question.