Generally rare but occasionally severe weight gain after switching to an integrase inhibitor in virally suppressed AGEhIV cohort participants

Recent studies have reported disproportionate weight gain associated with integrase strand transfer inhibitor (INSTI) initiation in antiretroviral therapy(ART)-naive people with HIV (PWH), particularly among black women. We investigated if HIV-positive AGEhIV participants with suppressed viremia switching to INSTI-containing ART experienced more weight gain compared to HIV-positive virally-suppressed non-switching and HIV-negative controls. In the AGEhIV cohort, standardized weight measurements were performed biennially. Participants switching to INSTI-containing ART were 1:2:2 propensity score-matched with controls by age, gender, ethnicity and body mass index. Mean weight changes and proportions experiencing >5% or >10% weight gain were compared between study-groups using linear mixed-effects models and logistic regression, respectively. 121 INSTI-switching participants and 242 participants from each of the control groups were selected. Across groups, median age was 53-55 years, 83-91% were male and 88-93% white. Mean weight change after switch among INSTI-switching participants was +0.14 kg/year (95%CI -0.25, +0.54) and similar among HIV-positive [+0.13 kg/year (95%CI +0.07, +0.33; P = .9)] and HIV-negative [+0.18 kg/year (95%CI 0.00, +0.37; P = .9)] controls. Weight gain >5% occurred in 28 (23.1%) INSTI-switching, 38 HIV-positive (15.7%, P = .085) and 32 HIV-negative controls (13.2%, P = .018). Weight gain >10% was rare. Switching to INSTI-containing ART in our cohort of predominantly white men on long-term ART was not associated with greater mean weight gain, but >5% weight gain was more common than in controls. These results suggest that not all, but only certain, PWH may be particularly prone to gain a clinically significant amount of weight as a result of switching to INSTI.