Drug Database: MK-8527

What is MK-8527?What is MK-8527?

What is MK-8527?

MK-8527 is an investigational drug that is being studied to prevent HIV.^3,4

MK-8527 belongs to a group of HIV drugs called nucleoside reverse transcriptase translocation inhibitors (NRTTIs). NRTTIs use several different methods to block an HIV enzyme called reverse transcriptase. By blocking reverse transcriptase, NNRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.^6,7

MK-8527 had previously been studied for HIV treatment; however, current Phase 3 studies are focused on the development of MK-8527 as a once-monthly oral tablet for HIV pre-exposure prophylaxis (PrEP).^3–5

To learn about how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

Select clinical trials of MK-8527Select clinical trials of MK-8527

Select clinical trials of MK-8527

Study Names: MK-8527-007; NCT06045507

Phase: 2a
Status: This study has been completed.
Locations: United States, Israel, and South Africa
Purpose: The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of once-monthly oral MK-8527 given at 3 different dose levels in participants at low risk for HIV.⁸
Selected Study Results: Results presented at IAS 2025 demonstrated that MK-8527, at all doses studied, was generally well tolerated and had a safety profile comparable to placebo. The levels of MK-8527 in the body increased proportionally with increased dose.⁹

Study Names: EXPrESSIVE-10; MK-8527-010; NCT07071623

Phase: 3
Status: See the ClinicalTrials.gov record for this study’s status.
Locations: Kenya, South Africa, and Uganda
Purpose: The purpose of this study is to evaluate the safety and efficacy of once-monthly oral MK-8527 as HIV PrEP in sexually active women and adolescent girls in sub-Saharan Africa.^4,10

Study Names: EXPrESSIVE-11; MK-8527-011; NCT07044297

Phase: 3
Status: This study is currently recruiting participants.
Locations: United States and Dominican Republic
Purpose: The purpose of this study is to evaluate the safety and efficacy of once-monthly oral MK-8527 as HIV PrEP in sexually active adults and adolescents who could benefit from PrEP.^3,10

For more details on the studies listed above, see the Health Professional version of this drug summary.

Other studies of MK-8527 are ongoing or planned, including the following Phase 1 trials:

• MK-8527-009 (NCT06580587): A study evaluating drug concentrations of MK-8527 in breast milk following a single oral dose in healthy lactating female participants. This study is currently recruiting participants.¹¹
• MK-8527-014 (NCT07063238): A study evaluating the effect of a single oral higher-than-normal dose of MK-8527 on the heart rhythm in healthy adults. This study is currently recruiting participants.¹²
• MK-8527-015 (NCT07025551): A trial evaluating the pharmacokinetics of a single oral dose of MK-8527 in participants with mild or moderate liver impairment. This study is currently recruiting participants.¹³

Two additional Phase 1 trials (MK-8527-001 and MK-8527-003) evaluating the safety and pharmacokinetics of increasing single and multiple oral doses of MK-8527 in adults without HIV have been completed. Results are available from Clin Transl Sci (2025).¹⁴

What side effects might MK-8527 cause?What side effects might MK-8527 cause?

What side effects might MK-8527 cause?

One goal of HIV research is to identify safe new drugs that have fewer side effects. In the MK-8527-007 (NCT06045507) study discussed under the previous section, the safety profile of MK-8527 at all doses studied was similar to that of placebo. Most of the drug-related side effects that occurred were mild or moderate and went away during the study. One participant had a serious drug-related side effect of spontaneous abortion. Two participants discontinued MK-8527 because of a drug-related side effect—one participant due to mild decreases in CD4 and/or lymphocyte counts and another participant due to moderate numbness or loss of sensation.^8,9

Participants who met criteria for study drug discontinuation due to reductions in CD4 and/or lymphocyte counts, as specified by the study protocol, had their levels return to baseline within 11 weeks. Investigators determined that the changes in CD4 and total lymphocyte counts seen with MK-8527 were not clinically significant.⁹

Because MK-8527 is still being studied, information on possible side effects of the drug is not complete. As testing of MK-8527 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying MK-8527?Where can I get more information about clinical trials studying MK-8527?

Where can I get more information about clinical trials studying MK-8527?

More information about MK-8527-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests.)

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

ReferencesReferences

References

1. National Center for Biotechnology Information. PubChem Compound Summary for CID 118389446. Accessed September 19, 2025
2. Merck website. Our pipeline at a glance. Accessed September 19, 2025
3. Merck Sharp & Dohme LLC. A Phase 3, randomized, active-controlled, double-blind clinical study to evaluate the efficacy and safety of MK-8527 oral once-monthly as HIV-1 preexposure prophylaxis. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 26, 2025. NLM Identifier: NCT07044297. Accessed September 19, 2025
4. Merck Sharp & Dohme LLC. A Phase 3, randomized, active-controlled, double-blind clinical study to evaluate the efficacy and safety of MK-8527 oral once-monthly as HIV-1 preexposure prophylaxis in women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 8, 2025. NLM Identifier: NCT07071623. Accessed September 19, 2025
5. Carstens RP, Kapoor Y, Vargo R, et al. Single dose administration of MK-8527, a novel nRTTI, in adults with HIV-1. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO. Abstract 115. Accessed September 19, 2025
6. Raheem IT, Girijavallabhan V, Fillgrove KL, et al. MK-8527 is a novel inhibitor of HIV-1 reverse transcriptase translocation with potential for extended-duration dosing. PLOS Biol. 2025;23(8):e3003308. doi:10.1371/journal.pbio.3003308. Accessed September 19, 2025
7. Raheem I, Fillgrove K S, O’Donnell G, et al. Discovery of MK-8527: a long-acting HIV-1 nucleoside reverse transcriptase translocation inhibitor. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO. Poster 638. Accessed September 19, 2025
8. Merck Sharp & Dohme LLC. A Phase 2a, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of oral MK-8527 once monthly in participants at low-risk for HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 13, 2023. NLM Identifier: NCT06045507. Accessed September 19, 2025
9. Mayer K, Kotze P, Lombaard J, et al. Safety and pharmacokinetics of MK-8527 oral once-monthly: a Phase 2 study in adults at low risk of HIV-1 exposure. IAS Conference on HIV Science; July 13-17, 2025; Kigali, Rwanda. Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2025. Accessed September 19, 2025
10. Merck: Press release, dated July 14, 2025. Merck to initiate Phase 3 trials for investigational once-monthly HIV prevention pill. Accessed September 19, 2025
11. Merck Sharp & Dohme LLC. A clinical study to evaluate the breast milk, plasma and whole blood pharmacokinetics of MK-8527 in healthy lactating female participants. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 28, 2024. NLM Identifier: NCT06580587. Accessed September 19, 2025
12. Merck Sharp & Dohme LLC. A double-blind, placebo-controlled and active-controlled trial to evaluate the effect of a supratherapeutic dose of MK-8527 on the QTc interval in healthy adult participants. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 3, 2025. NLM Identifier: NCT07063238. Accessed September 19, 2025
13. Merck Sharp & Dohme LLC. An open-label, single-dose study to evaluate the pharmacokinetics of MK-8527 in participants with mild and moderate hepatic impairment. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 9, 2025. NLM Identifier: NCT07025551. Accessed September 19, 2025
14. Gillespie G, Carstens RP, Zang X, et al. Safety and pharmacokinetics of MK‐8527 in adults without HIV. Clin Transl Sci. 2025;18(9):e70331. doi:10.1111/cts.70331. Accessed September 19, 2025