Efficacy, Safety, and Tolerability of Switching From Bictegravir/Emtricitabine/Tenofovir Alafenamide to Dolutegravir/Lamivudine Among Adults With Virologically Suppressed HIV: The DYAD Study

Abstract

Background In TANGO and SALSA, switching to dolutegravir/lamivudine (DTG/3TC) was noninferior compared to continuing baseline regimen in treatment-experienced adults, however few switched from bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF). Here, we present efficacy and safety of switching to DTG/3TC compared with continuing B/F/TAF in virologically suppressed adults. Methods DYAD is an open-label clinical trial that randomized adults with HIV-1 RNA<50 copies/mL and no prior virologic failure (2:1) to switch to once-daily fixed-dose DTG/3TC or remain on B/F/TAF. Primary endpoint is the proportion with HIV-1 RNA≥50 c/mL at Week (W) 48 (FDA snapshot algorithm, ITT-E population, 6% noninferiority margin). Results Overall, 222 adults (16% women; 51% aged ≥50 years; 28% Black) were randomized. At W48, 6 (4%) on DTG/3TC and 5 (7%) on B/F/TAF had HIV-1 RNA≥50 c/mL (treatment difference -2.8%, 95% confidence interval [-11.4%, 3.1%]) meeting noninferiority criteria. Through W48, 18 participants (12 on DTG/3TC, 6 on B/F/TAF) met confirmed virologic withdrawal (CVW) criteria, and 2/18 had resistance. One B/F/TAF CVW developed M184M/I and G140G/S at W12, and one DTG/3TC CVW had M184V at W12. One non-CVW DTG/3TC participant developed M184V and K65R at W12. Drug-related adverse events (AEs) and withdrawals due to AEs occurred in 31 (21%) and 6 (4%) participants with DTG/3TC and 2 (3%) and 0 participants with B/F/TAF, respectively. Conclusions Switching to DTG/3TC was noninferior to continuing B/F/TAF among virologically suppressed adults at W48. Drug-related AEs-and-withdrawals were higher in the DTG/3TC arm which is likely consistent with the open-label nature of this switch study.