Altered Lipid and Neurotransmitter Metabolism as Potential Mechanisms of Weight Gain in Women With HIV Initiating INSTIs in a Pilot Study.

OBJECTIVE

This pilot study used metabolomics to provide insights into metabolic alterations of integrase strand transfer inhibitor (INSTI)-associated weight gain among women with HIV.

METHODS

The study included 33 virally suppressed women with HIV who switched to or added an INSTI. Plasma samples collected 6-12 months pre- (visit 1) and 1-6 months post-INSTI add/switch (visit 2) were analyzed with liquid chromatography-mass spectrometry-based high-resolution metabolomics. The baseline plasma metabolome and changes in metabolomic signatures (from visit 1 to visit 2) were compared in women who experienced ≥5% weight gain (n = 18) over 1-2 years vs those who maintained/lost body weight (n = 15).

RESULTS

Median age was 53 (Q1 47, Q3 55) years, 94% were Black, and baseline body mass index was 34.2 (Q1 30.6, Q3 38.5) kg/m 2 . The median weight change was +9.20 kg (Q1-Q3 6.77-15.13 kg) and -0.68 kg (Q1-Q3 -5.14 to 0.00 kg) for the weight gain vs maintained/lost weight groups, respectively. A total of 820 metabolites spanning 9 enriched metabolic pathways, including amino acid (eg, tryptophan) and micronutrient pathways (eg, vitamin E) differed between weight groups before INSTI use ( P < 0.05). A total of 1147 metabolites spanning 10 enriched pathways, particularly lipid pathways, exhibited a significant group x time interaction effect ( P < 0.05), with an overall pattern of decreased free fatty acids over time among women who gained weight.

CONCLUSIONS

Several metabolic pathways at baseline and within 6 months were associated with weight gain in women initiating INSTIs. Acute changes in lipid metabolism after INSTI initiation provide potential insights into the pathophysiology of weight gain in this population.