Increased weight has been observed among treatment-naïve-and-experienced people living with HIV initiating bictegravir (BIC) and dolutegravir (DTG). Here, we report changes in weight and body mass index (BMI) following switch to a BIC versus DTG-based regimen (DBR) through 144 weeks. This observational study collected demographics, clinical characteristics, weight, and BMI from virologically suppressed adults switched to BIC/emtricitabine/tenofovir alafenamide (TAF), emtricitabine/TAF plus DTG, DTG/abacavir/lamivudine, DTG/rilpivirine (RPV), and DTG/lamivudine 2 years prior to switch through 144 weeks post-switch. Linear spline models were fit to estimate and compare the trajectories of weight and BMI changes observed pre-and-post-switch. Adjusted piecewise linear mixed-effects models were fit to examine factors associated with weight and BMI change pre-and-post-switch. At week 144, switching to BIC/emtricitabine/TAF versus a DBR were both associated with lower annualized weight gain post-switch (-0.88 kg/year vs -0.39 kg/year respectively, P = .15). DTG plus emtricitabine/TAF switches had the highest annualized weight gain (0.68 kg/year, 95% confidence interval: -0.32, 1.65) whereas, DTG/RPV switches had the lowest annualized weight gain (-2.22 kg/year, 95% confidence interval: -3.69, -0.62) post-switch. DTG/RPV and BIC/emtricitabine/TAF switches were the only groups with significantly lower annualized weight gain post-switch at week 144. Baseline BMI <
18.5 kg/m2 was associated with the highest annualized weight gain post-switch, whereas switching from protease inhibitors and self-report of dieting were associated with the lowest annualized weight gain post-switch. At week 144, switching to a BIC versus DBR were both associated with lower annualized weight gain post-switch among a large and diverse cohort of treatment-experienced people living with HIV.