Differential effects of switching to integrase strand transfer inhibitors on the gut microbiota and markers of HIV disease progression.

Abstract

Background: Unwanted weight gain is often reported in people living with HIV (PWH) who start on or switch to integrase strand transfer inhibitors (INSTI). Mechanisms are incompletely understood. An unintended off-target of INSTI might be the gut microbiota.

Methods: We explored the fecal microbiota of treated aviremic PWH (n = 70) who switched from efavirenz (EFV)- to a bictegravir (BIC)-based regimen. 16S rRNA sequencing, and enzyme-linked immunosorbent assays were used to characterize the fecal microbiota and quantify markers of HIV disease progression. A cohort of high-risk HIV-negative individuals (n = 18) was included to address differential effects of antiretroviral therapy (ART) on the fecal microbiota.

Results: This real-life cohort was predominantly male (n = 63) and mostly men who have sex with men (n = 40). All PWH were on the same antiretroviral regimen for at least 1 year; the mean time on ART was 10.83 ± 5.530 years and all had undetectable plasma viral loads (< 40 HIV-1 RNA copies/mL). PWH gained a median weight of 3.375 kg and the mean percent weight change relative to baseline was 4.32%. Seven (10%) PWH gained significant weight (> 10% relative to baseline). Switching to a BIC-based regimen had contrasting effects. PWH on BIC/FTC/TAF showed decreased microbial translocation (soluble CD14, sCD14), decreased enterocyte damage (intestinal fatty-acid binding protein, I-FABP), and increased alpha diversity (richness and shannon); all indicative of a better restoration of the gut mucosa and microbiota. Conversely, increases in sCD163, monocyte chemoattractant protein 1 (MCP-1) and decreases in adiponectin, markers linked to cardiovascular disease, insulin resistance and adiposity, were unfavorable.

Conclusion: Our data suggest that INSTI have a less detrimental effect on the gut microbiota compared to EFV-based regimen. The link between weight gain on INSTI and the gut microbiota was not readily apparent.