VOGUE: Non-Inferior Efficacy of Dolutegravir/Lamivudine Versus Bictegravir/Emtricitabine/Tenofovir Alafenamide in Adults With HIV-1 Naive to Treatment

Background Antiretroviral therapy (ART) that achieves virologic suppression using fewer antiretroviral agents is an optimized approach to HIV treatment initiation. VOGUE is the first randomized, head-to-head study comparing the 2-drug regimen dolutegravir/lamivudine (DTG/3TC) with the 3-drug regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as initial ART, including among individuals with high viral loads (VLs) and/or low CD4+ cell counts. Methods This phase 3b, randomized (1:1), open-label, non-inferiority study compared DTG/3TC vs BIC/FTC/TAF as first-line ART in adults with HIV-1. Participants were enrolled without baseline VL or CD4+ cell count restrictions and initiated treatment before availability of resistance testing results. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL at Week 48 (Snapshot; -10% non-inferiority margin). Results Among 509 randomized participants (DTG/3TC, n=254; BIC/FTC/TAF, n=255), 47% had baseline VL ≥100,000 copies/mL and 16% had CD4+ cell count <200 cells/mm3. At Week 48, DTG/3TC demonstrated non-inferior efficacy to BIC/FTC/TAF, with HIV-1 RNA <50 copies/mL achieved in 89% and 92% of participants, respectively (adjusted difference, -3% [95% CI, -8%, 2%]). Median time to virologic suppression was rapid (4.1 weeks) in both groups. Confirmed virologic withdrawals were similar between groups (n=7 each), with no treatment-emergent resistance identified. Safety outcomes were comparable. Conclusions Dolutegravir/Lamivudine demonstrated non-inferior efficacy to BIC/FTC/TAF as initial ART, with no treatment-emergent resistance through Week 48. These findings establish DTG/3TC as an effective and simplified initial ART regimen across a broad clinical spectrum.