Linking gut microbiome to HIV-1 reservoir size in people living with HIV

The gut microbiome is altered during HIV-1 infection and contributes to immune dysfunction and inflammation in people living with HIV (PLWH), these changes may persist despite effective antiretroviral therapy (ART). We explored the associations between the fecal gut microbiome and blood HIV-1 reservoir size in PLWH (n = 30) on long-term ART. The intact proviral DNA assay (IPDA) and shotgun metagenomic sequencing were performed to identify microbial species and metabolic pathways associated with the size of the HIV-1 reservoir. PLWH with a smaller intact reservoir exhibited lower evenness compared to individuals with a larger intact reservoir. We found that Phocaeicola plebeius and Lachnospira sp000437735 were significantly enriched in individuals with a smaller intact reservoir and lower intact-to-total proviral ratio, respectively. We observed a negative association between Faecalibacterium prausnitzii and a positive association of Prevotella copri, with the intact proviral reservoir size. Additionally, the metabolic pathways of glycolysis and branched-chain amino acid biosynthesis were enriched in individuals with larger reservoir. HIV reservoir size in blood is associated with gut microbiome evenness, specific metabolic pathways and microbial signatures, including Lachnospira, Prevotella, and Faecalibacterium. Our findings underscore the potential role of the gut microbiome in viral persistence, raising the possibility that modulating microbial composition could influence the HIV reservoir.