The safety and efficacy of maintenance with doravirine/lamivudine/tenofovir through 192 weeks in adults with HIV-1: results from the DRIVE-AHEAD clinical trial
BACKGROUND: DRIVE-AHEAD is a phase 3 trial with a completed double-blind phase comparing doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) to efavirenz/emtricitabine/TDF (EFV/FTC/TDF) and an ongoing open-label extension. At 48 and 96 weeks, once-daily DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF, superior CNS safety, and a favorable lipid profile. Here we present efficacy and safety results through Week 192 (W192).
METHODS: Participants who completed the 96-week double-blind phase and met inclusion criteria were eligible to receive open-label DOR/TDF/3TC in a 96-week extension. Efficacy and safety were assessed in 2 groups: participants initially randomized to DOR/3TC/TDF and maintained on DOR/3TC/TDF (N=291) and those who switched from EFV/FTC/TDF to DOR/3TC/TDF (N=269).
RESULTS: HIV-1 RNA <50 copies/mL was maintained through W192 in 84.9% of participants who continued DOR/3TC/TDF and 80.3% of those who switched to DOR/3TC/TDF. Protocol-defined virologic failure occurred in 2.4% and 4.8%, respectively, and the development of genotypic resistance was low in both groups (table). Discontinuation due to adverse events was also low (table). Neuropsychiatric adverse event rates during the extension (6.2% and 9.3%, respectively) were substantially lower than during the base study (DOR/3TC/TDF group 26.4%; EFV/FTC/TDF group 58.5%). Fasting LDL-cholesterol, non-HDL-cholesterol, and triglycerides showed minimal change in participants maintained on DOR/3TC/TDF and were reduced in those who switched to DOR/3TC/TDF (table). Participants maintained on DOR/3TC/TDF had minimal weight gain after W96 (median 0.5 kg) and a small increase overall (median 2.0 kg; Day 1 through W192); participants who switched to DOR/3TC/TDF had a small increase after W96 (median 2.0 kg), similar to median weight gain in the base study (DOR/3TC/TDF 1.2 kg; EFV/FTC/TDF 1.0 kg).
CONCLUSIONS: Among participants who continued DOR/3TC/TDF in the open-label extension, high efficacy and favorable safety were maintained for an additional 96 weeks. In participants who switched from EFV/FTC/TDF, DOR/3TC/TDF maintained virologic suppression and demonstrated favorable safety for 96 weeks.
C. Orkin * (1), J.-M. Molina (2), K. Supparatpinyo (3), S. Kumar (4), H. Wan (4), V. Teal (4), E. Asante-Appiah (4), P. Sklar (4), H. Teppler (4), R. Lahoulou (5)
(1) Queen Mary University of London, London, United Kingdom, (2) Saint-Louis Hospital and University of Paris, Paris, France, (3) Chiang Mai University, Chiang Mai, Thailand, (4) Merck & Co., Inc., Kenilworth, United States, (5) MSD France, Puteaux, France