Exploratory Substudy of a Phase 2 Trial to Evaluate the Pharmacokinetic Effect of Once-Monthly Islatravir on Long-Acting Reversible Contraceptives.

Abstract

Background: People living with, or at risk of acquiring, HIV-1 may use hormonal long-acting reversible contraceptives (LARCs). Islatravir is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV-1. We aimed to evaluate the effects of once-monthly oral islatravir on the pharmacokinetics of LARCs.

Setting: This was an exploratory substudy of a double-blind, randomized, placebo-controlled, Phase 2a trial of once-monthly oral islatravir in adults at low risk of HIV-1 infection (MK-8591-016; NCT04003103).

Methods: Participants were randomized 2:2:1 to receive 6 once-monthly doses of oral islatravir 60 mg, oral islatravir 120 mg, or placebo. At randomization, participants using an etonogestrel-releasing implant, injectable medroxyprogesterone acetate, or injectable norethindrone enanthate could enroll in the LARC substudy. LARC use was not a stratification factor. Plasma samples for hormone concentrations were collected at normally scheduled study visits and assayed using high-performance liquid chromatographic-tandem mass spectrometric methods.

Results: The analyses included 36 participants (etonogestrel, n = 8; medroxyprogesterone acetate, n = 20; norethindrone enanthate, n = 9; one participant was in 2 groups due to contraceptive change mid-study). No differences in hormone concentrations were observed between islatravir groups and placebo. Although sampling was insufficient to characterize full pharmacokinetics parameters, hormone concentrations were above the thresholds for contraceptive effectiveness for 94.4% (34/36) of participants.

Conclusion: Coadministration with once-monthly islatravir does not appear to affect exposure to LARCs in people at low risk of HIV-1 infection. Due to the exploratory nature of this substudy, prospective studies are needed to verify these findings.