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DORAVIRINE IS NON-INFERIOR TO DARUNAVIR/R IN PHASE 3 TREATMENT-NAÏVE TRIAL AT WEEK 48
Jean-Michel Molina1, Kathleen Squires2, Paul E. Sax3, Pedro Cahn4, Johan Lombaard5, Edwin DeJesus6, Xia Xu7, Bach-Yen T. Nguyen7, George Hanna7, Carey Hwang7
1Hosp St Louis, Paris, France,2Thomas Jefferson University, Philadelphia, PA,3Brigham and Women's Hospital, Harvard Medical School, Boston, MA,4Fundación Huesped, Buenos Aires, Argentina,5Josha Research, Bloemfontein, South Africa,6Orlando Immunology Center, Orlando, FL,7Merck & Co., Inc., Kenilworth, NJ
Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with once-daily dosing and potent in vitro activity against the most common NNRTI resistant variants (K103N, Y181C, G190A). In a phase 2b study, DOR 100 mg once daily (QD) demonstrated similar efficacy to efavirenz, with favorable safety and tolerability through Week 48.
DRIVE-FORWARD is an ongoing, phase 3, multicenter, double-blind, non-inferiority trial in antiretroviral treatment-naïve adults with HIV-1 infection and pre-treatment HIV-1 RNA ≥1,000 c/mL. Participants were stratified by screening HIV-1 RNA (≤ or >100,000 c/mL) and investigator-selected NRTI backbone therapy (TDF/FTC or ABC/3TC) and randomized in a 1:1 ratio to receive DOR 100 mg QD or darunavir 800 mg with ritonavir 100 mg (DRV/r) QD, in combination with the selected NRTI, for up to 96 weeks. The primary endpoint was the proportion (%) of participants achieving HIV-1 RNA <50 c/mL at Week 48 (NC=F, FDA Snapshot approach) with predefined non-inferiority margin of 10%. A secondary objective was to evaluate the effects of DOR and DRV/r on fasting serum lipids.
Of 769 participants randomized, 766 (383 in each group) received study drug and were included in the efficacy and safety analyses (mean age 35.2 years, 84% male, 73% white, 87% on TDF/FTC). DOR was non-inferior to DRV/r on the primary endpoint, with 83.8% (321/383) and 79.9% (306/383), respectively, achieving HIV-1 RNA <50 c/mL at Week 48 (difference 3.9%, 95% CI [-1.6, 9.4]). In the subgroup with baseline HIV-1 RNA >100,000 c/mL, 81.0% (64/79) on DOR and 76.4% (55/72) on DRV/r achieved HIV-1 RNA <50 c/mL at Week 48 (OF approach). Adverse event rates (overall, serious, drug-related, and leading to treatment discontinuation) were similar across treatment groups (see table). The most common drug-related AEs (>5% in one or more treatment groups) were diarrhea (5.5%, 12.8%), nausea (6.5%, 7.6%), and headache (6.0%, 2.6%) for DOR and DRV/r, respectively. Fasting LDL-C and non-HDL-C were reduced by DOR and increased by DRV/r (see table) with statistically significant treatment differences (p<0.0001).
At Week 48, DOR demonstrated potent efficacy and was non-inferior to DRV/r on a background of 2 NRTIs in HIV-1 treatment-naïve adults. Efficacy was similar regardless of baseline HIV-1 RNA. DOR was generally safe and well-tolerated with a superior lipid profile for fasting LDL-C and non-HDL-C compared to DRV/r.