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Integrase inhibitor use associated with weight gain in women and incident diabetes mellitus.

Abstract

For this retrospective cohort study, we obtained clinical warehouse data for HIV+ patients between fiscal years 2007-17. We compared patients initiated on an InSTI to those started on an alternate regimen. Our primary outcome was percentage weight change from baseline at 24-months post-initiation using linear mixed effects model fit by restricted maximum likelihood (REML). Our secondary outcome was incident T2DM as defined by new prescription for antihyperglycemic medication within 18 months after ART start. Diabetes-free survival was estimated using Kaplan-Meier method, log-rank test, and Cox proportional-hazards model.

InSTIs were significantly associated with weight gain among females. We also observed an increased risk of incident DM amongst both sexes, however, unrelated to weight changes. Further prospective studies will be necessary to confirm this finding and investigate its mechanism.

The cohort included 1235 individuals initiating ART, 136 (11.0%) with an InSTI. InSTI use in women was significantly associated with greater weight gain compared to non-InSTIs (11.0%, 95% CI 5.22-16.8% p < 0.01) after adjusting for potential confounding variables. InSTI use was associated with more incident T2DM diagnoses compared to non-InSTI regimens (unadjusted hazard ratio = 3.27, p = 0.01) though incident T2DM was not associated with weight gain.

Excessive weight gain associated with integrase strand transfer inhibitor (InSTI) antiretrovirals is an emerging issue, however, the metabolic consequences of this effect have not been established. Our objective was to evaluate for InSTI-emergent weight gain and potential associated type 2 diabetes mellitus (T2DM) amongst a diverse HIV patient cohort.

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