Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study

Abstract

Objective: To study gut microbiota before and 24 weeks after a single antiretroviral agent switch.Design: HIV-positive patients with efavirenz (EFV) or a protease inhibitor (PI)-based antiretroviral therapy (ART) were randomized to switch EFV or PI to raltegravir (RAL group, n ¼ 19) or to continue unchanged ART (EFV/PI group, n ¼ 22). Age and weightmatched HIV-negative participants (n ¼ 10) were included for comparison.Methods: Microbiota was analyzed using 16S rRNA sequencing. Serum intestinal fatty acid-binding protein (I-FABP) and serum lipopolysaccharide-binding protein (LBP) were measured as gut permeability markers. Three-day food diaries were collected.Results: At week 24, microbiota diversity (Chao1 index) was higher in RAL than the EFV/PI group (P ¼ 0.014), and RAL group did not differ from HIV-negative participants. In subgroup analysis switching from EFV (P ¼ 0.043), but not from a PI to RAL increased Chao1. At week 24, RAL and EFV/PI group differed in the relative abundance of Prevotella 9 (higher in RAL, P ¼ 0.01), Phascolarctobacterium and Bacteroides (lower in RAL, P ¼ 0.01 and P ¼ 0.03). Dietary intakes did not change during the study and do not explain microbiota differences. Also, I-FABP and LBP remained unchanged. Conclusion:Here we demonstrate that a single ART agent switch caused microbiota alterations, most importantly, an increase in diversity with EFV to RAL switch. Previously, we reported weight gain, yet reduced inflammation in this cohort. The observed microbiota differences between RAL and EFV/PI groups may be associated with reduced inflammation and/or increase in weight. Further studies are needed to evaluate inflammatory and metabolic capacity of microbiota with ART switches.

Untangling the role of the microbiome across the stages of HIV disease

“…As characterized by Pinto-Cardoso et al [33], a cross-sectional examination of the fecal microbiomes of ARV-treated patients reveals that although individuals on long-term ART collectively have distinct diversity measures as compared to uninfected individuals, there remain modest but appreciable variations in measures of the microbiome and translocation markers between patients on differing regimens. Too, Hanttu et al [34] reported increased alpha diversity in individuals switching from an efavirenz-to a protease inhibitor-based regimen. Some of the confounding effects of cocktail regimens can be resolved by testing the effects of ARVsindividually or in combinationon bacterial taxa in vitro.…”