Objective: Evaluate the impact of initiating integrase strand transfer inhibitor (INSTI)- vs non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based regimens on weight and glycemia among people with HIV (PWH) and type 2 diabetes. Design: Cohort Study Methods: From multi-site HIV cohorts in the U.S. and Canada (2007–2022), we identified PWH with diabetes who newly initiated INSTI-, NNRTI-, or PI-based therapy. We used inverse probability of treatment–weighted (IPTW) generalized linear models to compare changes in weight and hemoglobin A1c (HbA1c) at approximately twelve months after ART initiation. We assessed time to ≥5% weight gain and to glucose-lowering therapy augmentation or HbA1c increase ≥0.5 percentage points with IPTW Cox regression. Results: Among 1,279 PWH with diabetes, 548 initiated an INSTI-based regimen, 511 an NNRTI-based regimen, and 220 a PI-based regimen. Compared with NNRTI users, INSTI users had greater adjusted mean weight gain (2.1 kg; 95% CI, 1.1–3.1) while the difference in HbA1c change was modest (0.2%; 95% CI, 0.0–0.5); both changes were similar between INSTI and PI users. INSTI users had higher risk of ≥5% weight gain (adjusted hazard ratio aHR, 1.35; 95% CI, 1.15–1.59) and glucose-lowering therapy augmentation or HbA1c increase ≥0.5% (aHR, 1.19; 95% CI, 1.02–1.41) compared with NNRTI users although similar risk vs PI users. Conclusions: Among PWH with diabetes, initiating INSTIs conferred modestly greater weight gain and worse glycemic outcomes vs NNRTIs, but outcomes comparable to PIs, which is recognized for adverse metabolic effects. These findings inform the metabolic implications of INSTIs and support clinical monitoring after ART initiation.
Hwang et al. (Tue,) studied this question.