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

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

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).

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.

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.