Efficacy and safety of doravirine/islatravir in heavily treatment-experienced participants living with HIV-1 from a randomized trial

Objective: This study evaluated the efficacy (Day 8) and safety (Week 49) of doravirine/islatravir (DOR/ISL 100 mg/0.75 mg) plus baseline antiretroviral therapy (ART) and optimized background therapy (OBT) in heavily treatment-experienced (HTE) adults living with detectable HIV-1 RNA. Design and methods: HTE adults with confirmed plasma viral load >500 copies/mL receiving a stable ART regimen for ≥3 months were randomly assigned 1:2:1:1 to receive once-daily ISL alone, DOR alone, DOR/ISL, or matching placebo for 7 days; at Day 8, baseline ART was optimized and all participants received DOR/ISL and OBT through Week 49. The primary efficacy endpoint was percentage of participants receiving DOR/ISL achieving ≥0.5 log 10 decline in viral load from baseline (Day 1) to Day 8. Secondary efficacy endpoints included HIV-1 RNA levels and CD4+ T-cell counts through Week 49. Results: Thirty-five of the planned 100 participants were enrolled; most were White (57.1%) and male (77.1%) with median age of 50 years. From Day 1 to 8, a ≥1.0 log 10 decrease in HIV-1 RNA was achieved in 85.7% of the DOR/ISL group compared with 0% of the placebo group. At Week 49, HIV-1 RNA <50 copies/mL was achieved in 22 participants (71.0%) and the mean increase in CD4+ T-cell count was 87 cells/mm 3 . Adverse events were reported in 29 participants (82.9%) through Week 49; 9 (25.7%) were considered related to DOR/ISL. Conclusions: DOR/ISL plus OBT improved HIV-1 suppression in HTE adults living with HIV-1 and was generally well tolerated. ClinicalTrials.gov: NCT04233216