Merck Announces New Trial Results for Islatravir Plus Doravirine in Antiretroviral-Naïve Adults With HIV-1

July 9, 2020

Both trial sub-analyses will be presented at the virtual 23rd International AIDS Conference.

Merck announced new findings from its phase 2b clinical trial which assessed islatravir, its investigational oral nucleoside reverse transcriptase translocation inhibitor (NRTTI) in combination with doravirine (Pifeltro, Merck) in antiretroviral treatment-naïve adults with HIV-1 infection, as well as analyses from its phase 3 DRIVE-SHIFT trial.

The latest analyses of these 2 trials will be offered at 2 oral presentations taking place at the 23rd International AIDS Conference, which has been made virtual in response to the novel coronavirus disease 2019 (COVID-19) pandemic.

Phase 2b Sub-Analysis of Investigational 2-Drug Regimen of Islatravir Plus Doravine

The international, multicenter, randomized, phase 2b clinical trial evaluated patients with HIV-1 infection by assigning them to 1 once-daily oral treatment group: islatravir 0.25 mg, 0.75 mg, or 2.25 mg in combination with doravirine 100 mg and lamivudine (3TC) 300 mg compared with doravirine 100 mg/3TC 300 mg/tenofovir disoproxil fumarate 300 mg (TDF).

After a minimum of 24 weeks of treatment, participants receiving islatravir with HIV-1 RNA less than 50 copies/mL that had not met protocol defined virologic failure (PDVF) criteria altered treatment course to receive a 2-drug treatment, including the same dose of islatravir, as well as doravirine 100 mg without 3TC.

The 48-week treatment demonstrated decreased rates of drug-related adverse events (AEs) in participants in the islatravir groups (7.8%) compared with the doravirine/3TC/TDF group (19.4%). The study found that instances of AEs were more frequent in the first 24 weeks compared with the second half of the trial.

At week 48, PDVF rates were low; all participants who discontinued due to PDVF expressed levels of HIV-1 RNA below the clinically significant level of 200 copies/mL. Observed low-level viremia was similar to those reported in previous studies that included treatment-naïve patients. Investigators stressed the importance of continuing research in this area of HIV-1 infection treatment.

Phase 3 Sub-Analysis of DRIVE-SHIFT Trial

The latest findings from the phase 3 DRIVE-SHIFT trial, which assessed patients that had shifted treatment to doravirine/3TC/TDF, found that weight changes in patients reflected the average change reported in HIV-negative adults in the United States. Following the treatment change, patients in the Immediate Switch group gained 1.4 kg, whereas those in the 2-year Delayed Switch Group gained 1.2 kg.

“The initiation of some types of antiretroviral therapy in people living with HIV has been associated with weight gain,” said Princy Kumar, MD, chief, division of infectious diseases and tropical medicine at MedStar Georgetown University Hospital and professor of medicine and microbiology, Georgetown University School of Medicine, Washington, DC. “Our post-hoc analysis of weight changes from the Phase 3 DRIVE-SHIFT trial showed weight changes with Delstrigo comparable to the average annual weight gain observed in the general adult population.”

Prescribing information for doravirine can be found here, and prescribing information for doravirine/3TC/TDF is available here

Reference:

  1. Merck Announces New Analyses Showing Additional Safety and Efficacy Data for Investigational Islatravir in Combination with Doravirine in Adults with HIV-1 Infection. News Release. Merck; July 6, 2020. Accessed July 7, 2020. https://www.mrknewsroom.com/newsroom/news-releases/news-details/2020/Merck-Announces-New-Analyses-Showing-Additional-Safety-and-Efficacy-Data-for-Investigational-Islatravir-in-Combination-with-Doravirine-in-Adults-with-HIV-1-Infection/default.aspx.