Get the content you want anytime you want.

Dual Therapy MK-8591 Plus Doravirine Efficacious in Treatment-Naive PLWH

A new class of treatments known as nucleoside transcriptase translocation inhibitors (NRTTIs) is showing promise in helping treatment-naïve people living with HIV (PLWH) achieve viral suppression.

At the recent 10th IAS Conference on HIV Science (IAS 2019) in Mexico, investigators presented 48-week efficacy and safety data from a study evaluating MK-8591, the first drug in this new class, in combination with doravirine (DOR), a recently approved non-nucleoside reverse transcriptase inhibitor.

For the first 24 weeks, participants in the phase 2b, randomized, double-blind, comparator-controlled, dose-ranging trial received 1 of 3 doses of MK-8591 (0.25 mg, 0.75 mg, or 2.25 mg) plus DOR (100 mg) and lamivudine (3TC [300 mg]) or DOR/3TC/tenofovir disoproxil fumarate (TDF) once daily with placebo. 

Participants taking MK-8591 who achieved HIV-1 RNA< 50 copies/mL were switched to a 2-drug regimen of MK-8591 and DOR after 24 weeks, with the primary efficacy end point comprising the overall proportion of participants at week 48 with HIV-1 RNA< 50 copies/mL using the US Food and Drug Administration snapshot approach.

Investigators defined virologic failure 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.

A total of 121 participants (mean age 31 years, 92.6% male, 76.0% white, 22% HIV-1 RNA>100,000 copies/ml) were included in the study. The percentage of participants who achieved HIV-1 RNA< 50 copies/mL in the 0.25mg, 0.75mg, 2.25mg MK-8591 dose groups was 89.7% (26/29), 90.0% (27/30), and 77.4% (24/31), respectively, at week 48. A total of 83.9% (26/31) of participants achieved it with DOR/3TC/TDF.

By week 48, 6 participants met the definition of protocol-defined virologic failure—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.

From baseline through week 48, the mean change in CD4+ T-cell count was similar for all groups, and 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%).

Drug-related adverse events (AEs) were reported by 19.4% of DOR/3TC/TDF participants compared with 7.8% of MK-8591 participants (in any dose group), although none of the MK-8591 AEs were considered serious.

“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,” investigators concluded.

The study, “MK-8591 at doses of 0.25 to 2.25 mg QD, in combination with doravirine establishes and maintains viral suppression through 48 weeks in treatment-naïve adults with HIV-1 infection,” was presented Wednesday, July 24 2019, at IAS 2019 in Mexico City, Mexico.
To stay informed on the latest in infectious disease news and developments, please sign up for our weekly newsletter.