Background: MK-8591 is the first nucleoside reverse transcriptase translocation inhibitor (NRTTI) in development for treatment of HIV-1 infection. Doravirine (DOR) is a recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We present efficacy and safety data for MK-8591 with DOR through 48 weeks.
Methods: Phase 2B, randomized, double-blind, comparator-controlled, dose-ranging trial to evaluate efficacy and safety of MK-8591 with DOR. For the first 24 weeks, equal proportions of participants received one of three doses of MK-8591 (0.25 mg, 0.75 mg, or 2.25 mg) plus DOR (100 mg) and 3TC (300 mg) or DOR/3TC/TDF once daily with placebo. After 24 weeks of treatment, participants taking MK-8591 who achieved HIV-1 RNA< 50 copies/mL switched to a two-drug regimen of MK-8591 and DOR. Efficacy endpoints included the overall proportion of participants at week 48 with HIV-1 RNA< 50 copies/mL using the FDA snapshot approach. Protocol-defined virologic failure (PDVF) was defined as rebound with confirmed HIV-1 RNA≥50 copies/mL after suppression or non-response with confirmed HIV-1 RNA≥50 copies/mL by week 48. Safety was assessed by adverse event (AE) reporting.
Results: 121 participants received drug and were included in analyses (mean age 31 yr, 92.6% male, 76.0% white, 22% HIV-1 RNA>100,000 copies/ml). At week 48, 89.7% (26/29), 90.0% (27/30), 77.4% (24/31), of participants achieved HIV-1 RNA< 50 copies/mL in the 0.25mg, 0.75mg, 2.25mg dose of MK-8591 respectively, compared to 83.9% (26/31) with DOR/3TC/TDF. The mean change in CD4+ T-cell count from baseline to week 48 was similar for all groups. The proportion of participants on the 2-drug regimen for 24 weeks with HIV-1 RNA< 50 copies/mL was similar across doses (88.9%-90.0%). Six participants by week 48 met the definition of PDVF, 5/90 (5.6%) in the MK-8591 groups (4 rebound, 1 non-response) and 1/31(3.2%) in the DOR/3TC/TDF group (rebound); none had HIV-1 RNA>200 copies/mL or documented resistance to study drugs. No serious drug-related AEs were reported by MK-8591 participants. A higher rate of drug-related AEs was reported for DOR/3TC/TDF (19.4%) participants compared with any of the doses of MK-8591 (combined 7.8%).
Conclusions: Similar proportion of participants achieved and maintained viral suppression at week 48 across all treatment groups. MK-8591+DOR was well tolerated regardless of dose.