(P28-32-26) Serum Metabolomic Signatures of Regional Anthropometric Changes in Women With HIV after Switching to Integrase Strand Transfer Inhibitors

Objectives: Women with HIV (WWH) often gain body weight after initiating integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART); we previously showed this weight gain is associated with inflammatory polyunsaturated fatty acid (PUFA) and oxylipin pathways. Here, we examined associations between changes in regional anthropometric measures and the serum metabolome in WWH receiving INSTIs.

Methods: We conducted untargeted serum metabolomics using liquid chromatography–mass spectrometry in 38 aviremic (HIV RNA < 200 copies/mL) WWH from the MACS/WIHS Combined Cohort Study (MWCCS) receiving INSTIs. Samples were collected 6–12 months pre-, 1–6 months post-, and 1–2 years post-INSTI initiation. Waist, hip, and thigh circumferences were measured at each visit and waist-to-hip ratio (WHR) calculated. Linear mixed-effects models with random intercepts evaluated associations among metabolite features, anthropometric measures, time, and their interactions, adjusting for covariates. Pathway enrichment analysis via mummichog identified coordinated metabolic domains.

Results: Participants’ mean age was 46 years, mean BMI was 33 kg/m², and 74% identified as Black. Waist circumference change was associated with 30 enriched pathways, largely lipid related and including pro-inflammatory PUFA pathways such as arachidonic acid metabolism. WHR change was associated with 31 pathways, sharing lipid enrichment but demonstrating a distinct profile. Hip circumference change was associated with 19 pathways, including PUFA enrichment. In contrast, thigh circumference change was associated with 20 pathways, largely characterized by amino acid metabolism, including branched-chain amino acid, tryptophan, and tyrosine pathways.

Conclusions: Regional anthropometric changes during INSTI-based ART showed compartment-specific metabolic remodeling. Consistent with prior weight gain findings, PUFA and inflammatory lipid pathways were enriched with measures of central adiposity. In contrast, thigh circumference changes exhibited amino acid–dominant signatures, likely reflecting muscle metabolism. These findings support inflammatory lipid links to weight gain among INSTI users, alongside distinct peripheral metabolic adaptations.

Funding Sources: NIH (R01 DK125246, U54AG062334, U01 HL146241, U01 HL146193, R03 AG066559, K24 HL176324)