Pipeline Research

This study will evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of islatravir (MK-8591) in combination with doravirine (DOR) and lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human immunodeficiency virus type 1 (HIV-1) infection.

Given intracellular pharmacology differences, these preclinical models may be a conservative estimate of EFdA’s intracellular pharmacokinetics and efficacy in humans.

Research scientists are working together to see if a combination of medications – lenacapavir and islatravir – can improve HIV management. Both of these medications have a big advantage over current antiretroviral therapy (ART): they can be taken once a week, rather than daily.

A phase 1 clinical trial was conducted to evaluate the DDI (drug-drug interactions) of islatravir and the combination of oral contraceptive levonorgestrel (LNG)/ethinyl estradiol (EE). The results of this trial support the use of LNG/EE contraceptives in combination with islatravir without dose adjustment.

Investigational new drug applications were halted for the oral and implant formulations of islatravir, a nucleoside reverse transcriptase translocation inhibitor, for pre-exposure prophylaxis (PrEP); the injectable formulation of islatravir for treatment and prophylaxis; and the oral doravirine/islatravir (DOR/ISL) once-daily treatment, the company announced this week.

The health regulator’s move is based on observations of a drop in T-cell counts in some participants receiving the drug in clinical studies, the company said. T-cells are a critical component of the immune system that help the body fight infections.

U.S. Food and Drug Administration (FDA) has placed clinical holds on the investigational new drug applications (INDs) for the oral and implant formulations of islatravir (MK-8591) for HIV-1 pre-exposure prophylaxis (PrEP); the injectable formulation of islatravir for HIV-1 treatment and prophylaxis; and the oral doravirine/islatravir (DOR/ISL) HIV-1 once-daily treatment.

News of trouble at Merck emerged last month when the company paused development of an asset, MK-8507, that was central to its plans to create an oral, once-weekly treatment for HIV patients. The action followed the discovery of falls in total lymphocyte and CD4+ T-cell counts in patients who took MK-8507 in combination with backbone

This temporary pause has been implemented out of an abundance of caution, to allow the companies to consider potential protocol adjustments to the trial in light of Merck’s announcement on November 18 regarding the decision to stop dosing in the Phase 2 IMAGINE-DR clinical trial (MK-8591-013) evaluating the once-weekly combination of MK-8507 and islatravir.

Data from a randomized phase I trial in adults without HIV-1 published in Nature Medicine suggest that subdermal implant of islatravir, a nucleoside reverse transcriptase translocation inhibitor, is a promising pre-exposure prophylaxis (PrEP) option for HIV-1.