Background:
Multiple studies have reported higher weight gain among people with HIV (PWH) with integrase strand transfer inhibitors (INSTIs), most notably in ART-naïve PWH and among women and Blacks/African Americans. However, knowledge gaps remain regarding long-term patterns of weight gain beyond the first two years after starting INSTI-based regimens in ART-experienced PWH.
Methods:
An analysis of the effect of INSTIs on body mass index (BMI) was conducted in a large international cohort of PWH enrolled in REPRIEVE using mixed effect models with time-on-study as a continuous covariate. A stratified analysis was done evaluating 2-year change in BMI among participants on their entry ART regimen for 0-2 years, 2-5 years, and 5 or more years.
Results:
On average, BMI increased by +0.23 kg/m2 per year (95% CI: 0.19-0.28) with an INSTI and +0.17 kg/m2 per year with a non-INSTI regimen (95% CI: 0.13-0.21). For participants on their ART regimen for 2 years or less prior to study entry, INSTI use over the next 2 years in the trial was associated with greater increase in BMI per year compared to non-INSTI users: (0.29 (95% CI: 0.23-0.35) vs 0.17 (95% CI: 0.11-0.22)) [Figure 1], particularly among women (0.51 (95% CI: 0.33-0.69) vs men 0.23 (95% CI: 0.06-0.40)) and Blacks/African Americans (0.38 (95% CI: 0.27-0.49) vs non-Black 0.11 (95% CI: 0.001-0.21)). There were no significant differences in rate of BMI change between those on INSTIs and those not on INSTIs among participants on their entry regimen for more than 2 years: (0.14 (95% CI: 0.07-0.22) vs (0.14 (95% CI: 0.05-0.23) 2-5 years; 0.24 (95% CI: 0.11-0.38) vs 0.20 (95% CI: 0.12-0.28) > 5 years). Participants with lower BMI at entry gained more weight over time. Among INSTI users, the highest BMI increase was associated with elvitegravir, regardless of TDF or TAF use. In sensitivity analyses, results were generally similar after accounting for differences in TDF and TAF use between groups.
Conclusions:
Among a global cohort of PWH in REPRIEVE, the average rate of change in BMI associated with INSTI use was modest over 2 years of observation, but most significant among those on their entry ART 0-2 years prior to the observation period. Women and Black /African American participants were more likely to gain excess weight with INSTI use during this period. Lower BMI at study entry was predictive of higher weight gain on INSTIs. These data provide reassurance that long-term INSTI use may not be associated with substantial ongoing weight gain among PWH.
2-year change in BMI by INSTI use stratified by duration of entry regimen