Background: MK-8591 is a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) in development for the treatment and prevention of HIV-1 infection. Doravirine (DOR) is a recently approved, non-nucleoside reverse transcriptase inhibitor (NNRTI). We present the tolerability, safety, and efficacy data for MK-8591 in combination with DOR and lamivudine (3TC) through 24 weeks, for treatment of HIV-1 infection.
Methods: Phase 2B, randomized, double-blind, active comparator-controlled, dose-ranging trial designed to evaluate safety, tolerability and efficacy of MK-8591 given in combination with DOR and 3TC. Eligible participants were HIV-1 infected treatment-naïve adults with pre-treatment HIV-1 RNA ≥1,000 copies/mL and CD4+ T-cell count >200 cells/mm3. Participants were randomized (1:1:1:1) to one of four once-daily treatments groups, receiving one of three doses for MK-8591 (0.25, 0.75, or 2.25mg) plus DOR (100mg) with 3TC (300mg) added for at least the first 24 weeks, or DOR/3TC/TDF, with appropriate placebo. Safety was assessed by adverse event (AE) reporting. Efficacy endpoint of interest at week 24 was HIV-1 RNA < 50 copies/mL. At week 24, participants taking MK-8591 with HIV-1 RNA < 50 copies/mL could switch to a two-drug regimen of MK-8591 and DOR.
Results: 121 participants received drug and were included in analyses (mean age 31yr, 92.6% male, 76.0% white, 22% HIV-1 RNA >100.000 copies/mL) with 29, 30, 31, and 31 participants in the 0.25mg, 0.75mg, 2.25mg dose of MK-8591, or DOR/3TC/TDF groups respectively. There were no deaths, serious drug-related AEs or discontinuations due to AEs in any treatment group. Lower rates of drug-related non-serious AEs were reported for MK-8591 groups [0.0% (0/29), 6.7% (2/30) and 6.5% (2/31) for 0.25mg, 0.75mg and 2.25mg dose respectively] compared with DOR/3TC/TDF (19.4%, 6/31). At week 24, 89.7% (26/29), 100% (30/30), 87.1% (27/31), of participants achieved HIV-1 RNA < 50 copies/mL in the 0.25mg, 0.75mg, 2.25mg dose of MK-8591 respectively, compared to 87.1% (27/31) who received DOR/3TC/TDF. No virologic failure was observed by week 24. Efficacy was consistent regardless of baseline HIV-1 RNA level.
Conclusions: MK-8591 was well tolerated regardless of dose. Similar proportion of participants achieved HIV-1 RNA< 50 copies/ml at week 24 in all treatment groups.