Effects of Early Antiretroviral Therapy on the Composition and Diversity of the Fecal Microbiome of SIV-infected Rhesus Macaques ().

HIV-infected people develop reproducible disruptions in their gastrointestinal microbiota. Despite the suppression of HIV viremia via long-term antiretroviral therapy (ART), alterations still occur in gut microbial diversity and the commensal microbiota. Mounting evidence suggests these microbial changes lead to the development of gut dysbiosis-persistent inflammation that damages the gut mucosa-and correlate with various immune defects. In this study, we examined how early ART intervention influences microbial diversity in SIV-infected rhesus macaques. Using 16S rRNA sequencing, we defined the fecal microbiome in macaques given daily ART beginning on either 3 or 7 d after SIV infection (dpi) and characterized changes in composition, α diversity, and β diversity from before infection through 112 dpi. The dominant phyla in the fecal samples before infection were , , , and . After SIV infection and ART, the relative abundance of and did not change significantly. Significant reductions in α diversity occurred across time when ART was initiated at 3 dpi but not at 7 dpi. Principal coordinate analysis of samples revealed a divergence in β diversity in both treatment groups after SIV infection, with significant differences depending on the timing of ART administration. These results indicate that although administration of ART at 3 or 7 dpi did not substantially alter fecal microbial composition, the timing of early ART measurably altered phylogenetic diversity.