Background:
Weight gain is often reported when virologically suppressed people living with HIV (PWHIV) switch to integrase inhibitors (INSTI). Reasons linking INSTI to weight gain are unclear and might be attributed to this HIV drug class, to coformulation with tenofovir alafenamide, and/or influenced by medications, lifestyle and environmental factors. One factor that could impact weight gain is the gut microbiota. Ample evidence exists on the reciprocal causal relationship between the gut microbiome and host metabolism. Here, we evaluated changes in the gut microbiota in aviremic PWHIV who switched from EFV/FTC/TDF to BIC/FTC/TAF.
Methods:
This is a prospective single-center cohort study. A total of 27 PWHIV, 14.8% females (n=4), median age of 42 (26-53) years, virologically-suppressed (mean of 8.51 ± 4.98 years), were included. Fecal samples were obtained pre and one-year (mean of 367.3 ± 10.52 days) postswitch, and subjected to 16S rRNA sequencing.
Results:
Alpha diversity (shannon) increased significantly postswitch (median 3.9 [3.5-4.1] compared to 2.8 [2.1-3.4] preswitch, p< 0.0001), this increase was observed for both sexes. Bacteroidota dominated, averaging 57.43% abundance preswitch, decreasing to 47.10% postswitch, with a concomitant increase in Firmicutes abundance (27.16% to 43.12%). The Firmicutes to Bacteroidota ratio, a putative marker of obesity and weight gain, increased postswitch (median 1.024 [0.50-1.739] versus 0.34 [0.146-1.023] preswitch, p=0.02). At genus level, Prevotella (males) and Bacteroides (females) dominated, Faecalibacterium (both sexes) and UCG_002 (males) increased while Fusobacterium (females) and Succinivibrio (both sexes) decreased postswitch. Principle-coordinate analysis revealed that microbial community clustering was mostly influenced by intra- and interpersonal variation (subjects) and sex, explaining 67.5% and 6.5% of the variance (PERMANOVA p=0.0001 and p= 0.002, respectively).
Conclusions:
The complex nature of weight gain associated with HIV drug classes remains to be elucidated, and might reflect contextual host-gut microbiota adaptations. The work presented here expands our understanding of weight gain associated with INSTI. Our findings suggest that switching to INSTI might modulate the gut microbiota, increasing its diversity and the abundance of Firmicutes in both sexes, favoring weight gain by affecting energy extraction. Long-term health implications and therapeutic avenues should be further investigated to prevent or manage weight gain on INSTI.