Darunavir/cobicistat/emtricitabine/tenofovir alafenamide versus dolutegravir /abacavir/lamivudine in antiretroviral-naïve adults (SYMTRI): a multicenter randomized open-label study (PReEC/RIS-57)

Abstract

Abstract Background D/C/F/TAF is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naïve patients are lacking. Methods Adult (>18 y) HIV-infected antiretroviral-naïve patients (HLA B5701– and HBV-negative), with VL ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or DTG/3TC/ABC after stratifying by viral load and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the ITT-exposed population (FDA snapshot analysis, 10% non-inferiority margin). Results Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. 40% had a baseline VL >100,000 copies/mL, and 13% had <200 CD4 cells/μL. Median weight was 73 kg and median BMI 24 kg/m 2. At 48 weeks, 79% (D/C/F/TAF) vs 82% (DTG/3TC/ABC) had VL <50 c/mL (difference –2.4%, 95%CI –11.3 to 6.6). 8% vs 4% experienced virologic failure but no RAMs emerged. 4% vs 6% had drug discontinuation due to adverse events. In the per protocol analysis, 94% vs 96% patients had VL <50 c/mL (difference –2%, 95%CI –8.1 to 3.5). There were no differences in CD4 cell count or weight changes. Conclusions We could not demonstrate the non-inferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial ART, although both regimens were similarly well tolerated.