(160) Safety and Pharmacokinetics of Mk-8527 Oral Once-Monthly: A Phase 2 Study in Adults at Low Risk of HIV-1 Exposure

Abstract Introduction Long-acting options for HIV-1 pre-exposure prophylaxis (PrEP) are needed. MK-8527 is a novel, oral, nucleoside reverse transcriptase translocation inhibitor (NRTTI) with pharmacokinetic properties supporting once monthly (QM) dosing. Objective We studied the safety and pharmacokinetics of MK-8527 oral QM in adults at low risk of HIV-1 exposure. Methods In this double-blind, multicenter study (NCT06045507), adults 18–65 years of age were randomized 2:2:2:1 to receive MK-8527 (3, 6, or 12 mg) or placebo QM for 6 months. Adverse events and laboratory tests were monitored through 8 weeks after the last dose. MK-8527 in plasma was measured for all participants. MK-8527-triphosphate (TP), the active form, in peripheral blood mononuclear cells (PBMCs) was measured in a subset of participants. Pharmacokinetic exposures for MK-8527 and MK-8527-TP were based on non-compartmental analysis of the sparse data collected in the study. Results 350 participants were enrolled (58.3% female; median age 28 years; 51.4% White, 41.4% Black/African American, 2.3% Asian) and received at least one dose of study intervention; 328 (93.7%) received all six doses. The incidence of adverse events was similar for MK-8527 and placebo (Table 1). No clinically. Conclusions MK-8527 was well tolerated with a similar safety profile to placebo in adults at low risk of HIV-1 exposure. The pharmacokinetics of MK-8527 and MK-8527-TP support the continued development of MK-8527 oral QM for PrEP. Disclosure Yes, this is sponsored by industry/sponsor: Merck & Co., Inc. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Merck & Co., Inc.