Real-World Assessment of Weight Change in People with HIV-1 After Initiating Integrase Strand Transfer Inhibitors or Protease Inhibitors

**Background:** Studies have shown an increase in weight among people living with human immunodeficiency virus (PLWH) who have also initiated integrase strand transfer inhibitors (INSTI). However, limited data are available regarding comparison of these changes with other antiretroviral regimens. **Objective:** To assess differences in weight gain after initiating INSTI- versus protease inhibitor (PI)-based regimens among treatment-naive PLWH overall, and among a subpopulation of females only. **Methods:** This retrospective, observational cohort study included data from the Optum® deidentified Electronic Health Record (EHR) database. Adult PLWH who initiated INSTI- or PI-based regimens between March 1, 2016 and June 30, 2018 (index date was the first INSTI or PI prescription in this period) with ≥12-month baseline and follow-up periods, ≥1 weight measure during each period, and no prior antiretroviral use were included. The last weight measure between 12 months pre- and 30 days post-index was defined as baseline weight; the last measure between the months 4 and 12 of follow-up was defined as post-weight. Weight change was reported as absolute change and proportion of patients with increased weight. Cohorts were balanced using propensity score (PS) matching. Multivariable models were used to compare outcomes of interest. **Results:** After matching, 1588 patients were included (794 per cohort). At baseline, 46% were <50 years old, 26% were females, 12% had Type II diabetes and 30% had hypertension (mean baseline weight: INSTI: 83 kg (183 lb), PI: 82 kg (181 lb); P = 0.3). The mean time to follow-up weight measure was 9.3 months; INSTI initiators had a 1.3 kg (2.9 lb) greater mean weight gain (95% CI: 0.5–2.0), and a higher proportion with ≥5% weight gain (30.7% vs 26.1%; [OR=1.3, 95% CI: 1.0–1.6]) than PI initiators. Differences in weight gain between regimens were larger among females; female INSTI initiators had a 2.5 kg (5.3 lb) greater mean weight gain (95% CI: 0.7–4.2) and a higher proportion with ≥5% weight gain (37.5% vs 26.4%; OR=1.7; 95% CI [1.1–2.6]) than PI initiators. **Conclusion:** In a real-world setting, compared to PI-based regimens, INSTI-based regimens are associated with greater weight gain for treatment-naive PLWH. This study may inform HIV treatment choice for health care providers.