Integrase inhibitor-based antiretroviral therapy drives gut microbiota remodeling and immune recovery in HIV infection.

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.