Minimal Disruption of the Rectal Microbiome in Acute and Early Untreated HIV Infection

Background: Alterations in the gut microbiome have been linked to chronic HIV infection, yet less is known about microbiome dynamics during the earliest phases of HIV acquisition. It remains unclear whether microbial changes precede or follow HIV infection, and whether specific taxa could serve as early biomarkers or modulators of disease progression. Setting: The San Diego Primary Infection Resource Consortium (PIRC), a large HIV resource infrastructure program that enrolled predominantly men who have sex with men in Southern California, USA. Methods: We analyzed rectal swabs from 316 participants, 86 without HIV, 100 with acute (≤30 days post-infection) and 130 with early (31-180 days) untreated HIV infection. 16S rRNA sequencing was used to characterize bacterial communities. Alpha and beta diversity metrics, and taxon-level relative abundance were compared across groups using generalized linear models and MaAsLin3, adjusting for confounders and correcting for false discovery rate (FDR). Results: No significant differences in Shannon and Pielou index or beta diversity were observed by HIV status or stage. However, HIV infection was independently associated with a modest reduction in microbial richness (observed species; p=0.039). Enterocloster clostridioformis was significantly depleted among people with HIV (aβ -1.31, FDR p<0.001). Among participants with HIV, relative abundance of Akkermansia muciniphila was positively correlated with plasma HIV RNA levels (aβ 0.48, FDR p=0.016). Conclusion: The rectal bacteriome remains largely preserved during the first six months of untreated HIV infection. Subtle taxon-specific changes may reflect early viro-immunological perturbations but suggest limited diagnostic and prognostic utility of microbiome profiling.