Alimatravir Oral Once Monthly in Adults With Low Likelihood of HIV Exposure: A Randomized, Double-Blind,...

Long-acting oral options for human immunodeficiency virus-1 (HIV-1) pre-exposure prophylaxis are needed to address challenges with adherence to once-daily regimens. Alimatravir is an oral nucleoside reverse transcriptase translocation inhibitor with pharmacokinetic properties supporting once-monthly dosing.

In this double-blind, placebo-controlled study, adults aged 18-65 years with low likelihood of HIV-1 exposure were randomly assigned 2:2:2:1 to receive 6 oral doses of alimatravir (3, 6, or 12 mg) or placebo once every 4 weeks. The primary outcome was the proportion of participants with adverse events through 8 weeks after the last dose, assessed in participants who received at least one dose of study intervention. Additional outcomes were the pharmacokinetics of alimatravir in plasma (all participants) and alimatravir-triphosphate in peripheral blood mononuclear cells (∼ 20 participants from each alimatravir dose group).

Three hundred fifty participants were included in the analyses (median age 28 years; 58% female): 301 received alimatravir 3 mg (n = 101), 6 mg (n = 101), or 12 mg (n = 99) and 49 received placebo. Adverse event rates were comparable for alimatravir 3 mg (61.4% [62/101]), 6 mg (68.3% [69/101]), 12 mg (66.7% [66/99]), and placebo (63.3% [31/49]). Study intervention was discontinued because of an adverse event in 1.0% (3/301) of participants who received alimatravir and 4.1% (2/49) who received placebo. Pharmacokinetic parameters for alimatravir and alimatravir-triphosphate were dose-proportional and support a once-monthly dosing interval.

The favorable safety, tolerability, and pharmacokinetics of alimatravir and alimatravir-triphosphate support continued development of alimatravir as oral monthly pre-exposure prophylaxis.

ClinicalTrials.gov Identifier NCT06045507; https://www.clinicaltrials.gov/search.