A 48-week, Randomized Controlled Trial of Doravirine for Individuals with HIV and Obesity on Integrase Inhibitors and Tenofovir Alafenamide: The Do IT Study (ACTG A5391).
Academic Article
Overview
abstract
BACKGROUND: Integrase inhibitors (INSTI) and tenofovir alafenamide (TAF) have been associated with greater weight gain compared to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and tenofovir disoproxil fumarate (TDF), but the effects of an antiretroviral regimen switch on weight are unclear. METHODS: This 48-week, 3 parallel group, open-label, multicenter, randomized controlled trial (NCT04636437) in people with HIV and obesity on an INSTI (bictegravir, dolutegravir, or raltegravir) with TAF/emtricitabine (FTC) assessed whether switching to the NNRTI doravirine (DOR) with TAF/FTC or TDF/FTC results in weight loss or stabilization. Treatment effects were estimated using linear regression adjusted for sex, race, and entry weight. RESULTS: Of 147 participants randomized, 145 initiated their assigned treatment. At entry, median age was 49 years; BMI was 34.9 kg/m2, and time on INSTI+TAF/FTC was 3.4 years; 49% were female and 53% Black. After 48 weeks, estimated mean change in weight was -0.47% (95% confidence interval [CI]: -2.09,1.14) for the DOR+TAF/FTC arm, -2.73% (-4.22, -1.23) for DOR+TDF/FTC, and -1.84% (-3.37, -0.30) for INSTI+TAF/FTC. Estimated mean difference in weight change at 48 weeks for DOR vs. INSTI (both with TAF/FTC) was 1.36 percentage points (97.5% CI: -1.20,3.92), and -0.89 percentage points (-3.34,1.57) for DOR+TDF/FTC vs. INSTI+TAF/FTC. There was no evidence of variation by sex or race, nor of treatment differences for changes in fasting lipids, insulin resistance, fat mass, or bone mineral density. CONCLUSIONS: In people with HIV and obesity, switching from an INSTI+TAF/FTC regimen to DOR/FTC with either TAF or TDF did not produce clinically meaningful differences in weight change or metabolic health after 48 weeks.
