Association between plasma concentrations of integrase strand transfer inhibitors and body weight gain in women with HIV

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BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are associated with body weight gain. We evaluated the association between plasma concentrations of dolutegravir (DTG), raltegravir (RAL), and elvitegravir (EVG) and body weight change in women with HIV (WWH). METHODS: We analyzed data from 2006 to 2017 among virologically suppressed (<200 copies/ml) WWH in the Women's Interagency HIV Study who switched or added either RAL, DTG, or EVG to their antiretroviral therapy (ART). Percent weight change was determined from weights collected 6-12 months before and after INSTI switch/add. Sparse plasma concentrations were measured 6-12 months after switch/add using LC/MS-MS assays. Area under the curve (AUC) was estimated from published models, refined using plasma concentrations. Linear models assessed the association between plasma concentration or AUC and weight change for each INSTI. RESULTS: 176 WWH contributed plasma concentrations with an average follow-up of 1.5 years; 24% were on RAL, 49% on DTG, and 27% on EVG. Mean age was 50 years, 63% Non-Hispanic Black, and average BMI was 31.1 kg/m 2 . Weight gain averaged +2.4% in those reporting RAL, +3.1% for DTG, and +4.0% EVG. RAL concentration was associated with weight gain ( P = 0.0291, FDR = 0.0582), but no AUC or other drug concentration associations were found. CONCLUSION: Higher RAL plasma concentrations were only modestly associated with percent body weight gain in WWH, unlike DTG or EVG. These findings do not suggest a consistent exposure-response relationship between INSTI concentrations and weight gain.

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