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

Abstract

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 Bacteroidetes, Firmicutes, Spirochaetes, and Proteobacteria. After SIV infection and ART, the relative abundance of Firmicutes and Bacteroidetes 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.