Drug Database: Alimatravir

Pharmacology

Pharmacology

Mechanism of Action

Nucleoside reverse transcriptase translocation inhibitor (NRTTI). Alimatravir, a deoxyadenosine analog, is a unique compound derived through structural modification of the benchmark NRTTI islatravir. In vitro, alimatravir has shown potent and specific activity against a diverse panel of HIV-1 subtypes and HIV-2.^5,6

Intracellularly, alimatravir is converted to its active triphosphate form (alimatravir-TP). As an NRTTI, alimatravir-TP inhibits HIV reverse transcriptase (RT) through multiple modes of action. Once incorporated into viral DNA, alimatravir-TP functions as an immediate chain terminator by blocking RT translocation. In instances where RT translocation does occur and an additional nucleotide is allowed to incorporate onto the viral DNA chain, alimatravir-TP acts as a delayed chain terminator by causing structural changes to the viral chain.^5,6

Alimatravir is currently in Phase 3 development as a once-monthly oral tablet for HIV pre-exposure prophylaxis (PrEP).^3,4

Half-life (T_½)

In a Phase 1 study (MK‐8527‐003) of multiple ascending weekly oral doses of alimatravir (5–40 mg) in healthy adult participants, the apparent terminal half-life of alimatravir and the active triphosphate (alimatravir-TP) was 24–81 hours and 216–291 hours, respectively.⁷

Select Clinical Trials

Select Clinical Trials

Study Identifiers: MK-8527-007; NCT06045507

Sponsor: Merck Sharp & Dohme LLC
Phase: 2a
Status: This study has been completed.
Study Purpose: The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of once-monthly oral alimatravir given at 3 different dose levels in participants at low risk for HIV.
Study Population:

• Participants were adults without HIV who had a low likelihood of acquiring HIV.
• Participants had no prior use of alimatravir or islatravir.⁸

Selected Study Results: Results presented at IAS 2025 demonstrated that alimatravir, at all doses studied, was generally well tolerated and had a safety profile comparable to placebo. The pharmacokinetics of alimatravir in plasma and alimatravir-TP in PBMCs were dose proportional.⁹

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

Sponsor: Merck Sharp & Dohme LLC
Phase: 3
Status: This study is currently recruiting participants.
Study Purpose: The purpose of this study is to evaluate the safety and efficacy of once-monthly oral alimatravir as HIV PrEP in sexually active women and adolescent girls in sub-Saharan Africa.
Study Population:

• Participants are sexually active women and adolescent girls (16 to 30 years of age) without HIV.
• Participants have never taken cabotegravir, lenacapavir, or any other long-acting HIV PrEP product in the past. ^4,10

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

Sponsor: Merck Sharp & Dohme LLC
Phase: 3
Status: This study is currently recruiting participants.
Study Purpose: The purpose of this study is to evaluate the safety and efficacy of once-monthly oral alimatravir as HIV PrEP in sexually active adults and adolescents who could benefit from PrEP.
Study Population:

• Participants are people without HIV who have a higher likelihood of HIV exposure.
• Participants have never taken cabotegravir, lenacapavir, or any other long-acting HIV PrEP product in the past.
• See the ClinicalTrials.gov record for additional information on eligibility criteria.^3,10

Multiple Phase 1 studies evaluating alimatravir have been completed or are ongoing or planned. Some of these studies are described below.

• MK-8527-009 (NCT06580587) was an open-label study that evaluated drug concentrations of alimatravir in breast milk following a single oral dose in healthy lactating female participants. This study has been completed.¹¹
• MK‐8527‐001 and MK‐8527‐003 (Eudra CT: 2016‐004647‐36 and 2018‐000846‐20) were trials evaluating the safety and pharmacokinetics of ascending single and multiple oral doses of alimatravir in adults without HIV. These studies have been completed, and results are available from Clin Transl Sci (2025).⁷

Adverse Events

Adverse Events

MK-8527-007 (NCT06045507)

In this Phase 2a study, adults without HIV received oral monthly doses of alimatravir (3 mg [n = 101], 6 mg [n = 101], or 12 mg [n = 99]) or placebo (n = 49) for up to 6 months. The safety profile of alimatravir at all doses studied was similar to that of placebo. The majority of drug-related adverse events (AEs) were Grade 1 or 2 and resolved during the study. One participant in the alimatravir 3-mg dose group experienced a drug-related serious adverse event (SAE) of spontaneous abortion. Two participants discontinued alimatravir because of a drug-related AE—Grade 1 decreases in CD4/lymphocyte counts in one participant and Grade 2 hypoesthesia in another participant.^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. Overall, the changes in CD4 and total lymphocyte counts seen with alimatravir were deemed clinically insignificant.⁹

Drug Interactions

Drug Interactions

In a Phase 1 study (NCT06893081) evaluating the effects of carbamazepine (a strong CYP3A4 inducer) on the pharmacokinetics (PK) of alimatravir in adults without HIV, the PK parameters of alimatravir when administered with or without carbamazepine were similar.¹²

A Phase 1 drug-drug interaction trial (NCT06783192) evaluated the effects of oral alimatravir on the PK of the oral hormonal contraceptive levonorgestrel (LNG)/ethinyl estradiol (EE) in adult (18 to 70 years of age) female participants without HIV. Results demonstrated that coadministration of alimatravir with LNG/EE had no significant effect on the PK of LNG or EE.^13,14

A Phase 1 study (NCT06816043) evaluated the effect of emtricitabine/tenofovir DF (FTC/TDF) on alimatravir-TP levels in adults without HIV. A single oral dose of alimatravir given 24 hours after multiple daily doses of FTC/TDF led to a minor (clinically insignificant) reduction in alimatravir-TP exposure in peripheral blood mononuclear cells (PBMCs) compared to alimatravir given alone. Alimatravir-TP trough concentrations in PBMCs were similar between alimatravir administered with FTC/TDF and alimatravir administered alone.¹⁵

References

References

1. National Center for Biotechnology Information. PubChem Compound Summary for CID 118389446. Accessed August 19, 2026
2. Merck website. Our pipeline at a glance. Accessed August 19, 2026
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 August 19, 2026
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 August 19, 2026
5. 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 August 19, 2026
6. 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 August 19, 2026
7. 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 August 19, 2026
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 August 19, 2026
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 August 19, 2026
10. Merck: Press release, dated July 14, 2025. Merck to initiate Phase 3 trials for investigational once-monthly HIV prevention pill. Accessed August 19, 2026
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 August 19, 2026
12. Carstens RP, Kapoor Y, Bhattacharyya A, et al. Open-label Phase 1 study to characterize the effects of a strong CYP3A4 inducer on the pharmacokinetics of MK-8527, a nucleoside reverse transcriptase translocation inhibitor, in adults without HIV. Abstract presented at: International AIDS Conference; July 26-31, 2026; Rio, Brazil. Abstract TUPEB125. Accessed August 19, 2026
13. Merck Sharp & Dohme LLC. A study to assess the effects of single oral doses of MK-8527 on the single-dose pharmacokinetics of an oral contraceptive (levonorgestrel and ethinyl estradiol) in healthy adult postmenopausal or oophorectomized female subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 14, 2025. NLM Identifier: NCT06783192. Accessed August 19, 2026
14. Carstens RP, Kapoor Y, Garrett GC, et al. Phase 1, open-label study to evaluate the drug interaction between MK-8527, an HIV-1 nucleoside reverse transcriptase translocation inhibitor, and the oral contraceptive levonorgestrel/ethinyl estradiol in healthy adult female participants. Poster presented at: International AIDS Conference; July 22-26, 2024; Munich, Germany. Poster WEPEB106. Accessed August 19, 2026
15. Carstens RP, Kapoor Y, Bhattacharyya A, et al. Open-label Phase 1 study of the effects of emtricitabine/tenofovir disoproxil fumarate on the pharmacokinetics of MK-8527, a nucleoside reverse transcriptase translocation inhibitor, in adults without HIV. Abstract presented at: International AIDS Conference; July 26-31, 2026; Rio, Brazil. Abstract WEPEC183. Accessed August 19, 2026

Last Reviewed: August 19, 2026