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Obesity Modifies the Relationship Between Raltegravir and Dolutegravir Hair Concentrations and Body Weight Gain in Women Living with HIV.
AIDS Research and Human Retroviruses 2023 May 5
Integrase strand-transfer inhibitors (INSTIs) are associated with weight gain in women living with HIV (WLH). Relationships between drug exposure, baseline obesity, and INSTI-associated weight gain remain unclear. Data from 2006-2016 were analyzed from virally-suppressed WLH enrolled in the Women's Interagency HIV Study who switched/added an INSTI to antiretroviral therapy: (raltegravir [RAL], dolutegravir [DTG], or elvitegravir [EVG]). Percent body weight change was calculated from weights obtained a median 6 months pre- and 14 months post-INSTI initiation. Hair concentrations were measured with validated LC-MS/MS assays. Baseline (pre-switch) weight status evaluated obese (body mass index, BMI, ≥30 kg/m2) vs non-obese (BMI<30 kg/m2). Mixed models examined the drug hair concentration*baseline obesity status interaction for each INSTI. There were 169 WLH included: 53(31%) switched to RAL, 72(43%) to DTG, and 44(26%) to EVG. Women were median age 47-52y, predominantly Non-Hispanic Black, median CD4 counts >500 cells/mm3, >75% with undetectable HIV-1 RNA. Over ~1y, women experienced median increases in body weight: 1.71% (-1.78, 5.00) with RAL; 2.40% (-2.82, 6.50) with EVG; 2.48% (-3.60, 7.88) with DTG. Baseline obesity status modified the relationship between hair concentrations and percent weight change for DTG and RAL (p's<0.05): higher DTG, yet lower RAL concentrations were associated with greater weight gain among non-obese women. Additional pharmacologic assessments are needed to understand the role of drug exposure in INSTI-associated weight gain.
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