Background: 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). The 48-week results of the phase 3, DRIVE-FORWARD trial showed that DOR was noninferior to DRV+r in treatment-naïve adults, with a superior lipid profile for fasting LDL-C and non-HDL-C. Herein we present the 96-week data.
Methods: HIV-1 infected, treatment-naïve adults were randomized to DOR (100 mg/d) or DRV+r (800/100 mg/d) with investigator-selected nucleoside reverse transcriptase inhibitors (NRTI): tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). Resistance-associated mutations to NNRTIs or NRTIs was an exclusion factor. Study was double-blinded until week 96. Participants were stratified by baseline HIV-1 RNA (≤ or >100,000 copies/mL) and background NRTI therapy. The proportion of participants achieving HIV-1 RNA < 50 copies/mL (FDA Snapshot Approach), adverse events (AEs), and fasting serum lipids effects at week 96 were assessed.
Results: Of 769 participants randomized, 766 (383 in each group) received study drug and were included in the analyses (mean age 35.2 years, 84% male, 73% white, 87% on TDF/FTC). At 96 weeks, DOR demonstrated higher efficacy versus DRV+r: 73.1% and 66.0% in the DOR and DRV+r groups, respectively, achieved HIV-1 RNA < 50 copies/mL; treatment difference 7.1% (95% CI: 0.5, 13.7), and responses were similar regardless of baseline characteristics (Table). Treatment-emergent resistance to any study drug occurred in 0.5% and 0.1% of DOR and DRV+r groups, respectively. AE rates (overall, serious, drug related, and leading to treatment discontinuation) were similar across groups. The most common AEs (>5%, week 0-96) were diarrhea (DOR 17.0%, DRV+r 23.8%), nausea (11.7%, 13.6%), headache (14.9%, 12.0%), and upper respiratory tract infection (13.3%, 7.8%). Pronounced differences between treatment arms in mean changes from baseline in LDL-C (DOR -0.44 mg/dL, DRV+r +14.0 mg/dL) and non-HDL-C (-0.48 mg/dL, +17.7 mg/dL) were seen in favor of DOR.
Conclusions: Through 96 weeks of therapy, DOR demonstrated greater antiviral activity versus DRV+r, was well tolerated, and exhibited a more favorable lipid profile in treatment-naïve adults with HIV-1 infection. DOR in combination with NRTIs provides an attractive alternative for the treatment of HIV-1 in treatment-naïve adults.