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)

Background: Integrase inhibitors (INSTI) and tenofovir alafenamide (TAF) have been associated with greater weight gain compared to nonnucleoside 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 the 147 participants randomized, 145 initiated their assigned treatment. At entry, median age was 49 years; body mass index was 34.9 kg/m², and time on INSTI + TAF/FTC was 3.4 years; 49% were female and 53% Black. After 48 weeks, the estimated mean change in weight was −0.47% (95% 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. The estimated mean difference in weight change at 48 weeks for DOR versus 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 versus 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.