Lack of a Clinically Meaningful Drug Interaction Between the HIV-1 Antiretroviral Agents Islatravir, Dolutegravir, and Tenofovir Disoproxil Fumarate.

ABSTRACT

Islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, is in clinical development for the treatment and prevention of HIV-1 infection. Because islatravir may be coadministered with other antiretroviral agents, assessment of potential drug-drug interactions are warranted. This phase 1, open-label, fixed-sequence, 2-period trial in adults without HIV (N = 12) assessed the safety and pharmacokinetic interactions of islatravir administered with dolutegravir and tenofovir disoproxil fumarate (TDF). In period 1, participants received a single oral dose of islatravir (20 mg). In period 2, participants received oral doses of dolutegravir (50 mg) and TDF (300 mg) once daily on days 1 through 11, with a single oral dose of islatravir (20 mg) coadministered on day 8. There were no clinically significant changes in islatravir, dolutegravir, or TDF pharmacokinetics following coadministration. Islatravir was generally well tolerated when administered alone or in combination with dolutegravir and TDF. Coadministration of islatravir, dolutegravir, and TDF is supported, with no clinically meaningful effect on pharmacokinetics, safety, or tolerability in participants without HIV.