Gut microbiota and weight gain in people with HIV on integrase inhibitors: a five-year longitudinal study.

Objectives: To evaluate the relationship between the gut microbiota composition and significant weight gain in virologically-suppressed people with HIV (PWH) on antiretroviral therapy.

Methods: This 5-year prospective longitudinal study included virologically-suppressed PWH receiving regimens based on the integrase strand transfer inhibitors (INSTIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs). Body weight was measured annually, with significant weight gain defined as a ≥10% increase between consecutive measurements or compared to baseline. Gut microbiota profiling was conducted using 16S rRNA sequencing (V3-V4 regions) via the Illumina MiSeq platform.

Results: 202 participants were recruited, with 169 completing the 240-week follow-up. Among these, 63 remained on INSTI-based, 79 on NNRTI-based and 27 on NNRTI + INSTI-based regimens. Median (interquartile range (IQR)) 5-year weight gain was 1.3 (-2.8 to 4.5) kg. Significant weight gain occurred in 70 (34.7%) participants, including 20 (9.9%) with ≥10% gain between consecutive measurements and 50 (24.8%) from baseline. No significant differences were observed in adjusted α- and β-diversity indices between groups defined by weight gain. Adjusted analysis of compositions of microbiomes with bias correction 2 model showed that weight gain was associated with the genera Dialister and Tyzzerella_4, whereas Phascolarctobacterium was enriched in those without significant weight gain. While overall weight gain did not differ between INSTI-based and NNRTI-based groups, participants on INSTIs-based regimens showed higher relative abundances of bacteria linked to weight gain, like Tyzzerella_4 (0.05% versus 0.02%, P = 0.017) and Lactobacillus (0.29% versus 0.22%, P = 0.009).

Conclusions: Significant weight gain in the PWH is associated with distinct gut microbiota profiles. The enrichment of weight gain-associated taxa, such as Tyzzerella_4 and Lactobacillus, in individuals on INSTI-based regimens suggests a potential microbiota-mediated mechanism modulating metabolic outcomes.