Phase 3 Trials Begin for Once-Monthly Oral HIV Prevention Pill

Two global phase 3 clinical trials have been launched to evaluate the safety, efficacy, and tolerability of MK-8527, an investigational once-monthly oral nucleoside reverse transcriptase translocation inhibitor (NRTTI) for HIV pre-exposure prophylaxis (PrEP). The trials will compare MK-8527 to daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), the current standard of care, Merck announced in a press release.

The EXPrESSIVE-11 trial (NCT07044297) will enroll 4390 sexually active individuals at higher risk of HIV-1 infection in 16 countries, with enrollment beginning in August 2025. The EXPrESSIVE-10 trial will enroll 4580 adolescent girls and women aged 16 to 30 years in Kenya, South Africa, and Uganda and will begin enrolling in the coming months.

The phase 3 program is sponsored by Merck in collaboration with the Bill & Melinda Gates Foundation. The International Clinical Research Center (ICRC) at the University of Washington and the University of Alabama at Birmingham will lead the EXPrESSIVE-10 trial. The Gates Foundation is providing grant support for trial site operations, community engagement, and recruitment strategies.

Phase 2 results supporting advancement to phase 3 came from a double-blind, multicenter study (NCT06045507) of 350 adults with low risk of HIV-1 exposure. Participants received 3 mg, 6 mg, or 12 mg MK-8527 or placebo once monthly for 6 months. Adverse event rates were similar between treatment and placebo arms, and no clinically meaningful changes were observed in laboratory values, including CD4 T-cell counts. The pharmacokinetics of MK-8527 and its active metabolite MK-8527-TP support its further development.

Findings from the phase 2 trial were presented at the opening press conference of the 13th International AIDS Society (IAS) Conference on HIV Science.

MK-8527 works by inhibiting reverse transcriptase through multiple mechanisms, including inhibition of translocation and delayed chain termination.

“With only 18% of global PrEP need currently met, there is a clear and urgent need for options like MK-8527 that may offer the ability to prevent infection. These Phase 3 trials are a key step toward translating progress into longer-acting options that could help turn the tide on HIV," Trevor Mundel, president of global health at the Gates Foundation, said in a press release.

Source: Merck to initiate phase 3 trials for investigational once-monthly HIV prevention pill. News release. Merck. July 14, 2025. Accessed July 17, 2025. https://www.merck.com/news/merck-to-initiate-phase-3-trials-for-investigational-once-monthly-hiv-prevention-pill/