Drug Database: Ulonivirine

What is ulonivirine?What is ulonivirine?

What is ulonivirine?

Ulonivirine is an investigational drug that is being studied to treat HIV .²

Ulonivirine belongs to a group of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).³ NNRTIs attach to and 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.

Ulonivirine may be effective against certain HIV strains that are resistant to other HIV drugs.^3,4

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 ulonivirineSelect clinical trials of ulonivirine

Select clinical trials of ulonivirine

Study Names: IMAGINE-DR; MK-8591-013; NCT04564547

Phase: 2b
Status: This study has been completed.
Locations: United States, France, and Switzerland
Purpose: The purpose of this study was to evaluate a switch to a once-weekly regimen consisting of the investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) islatravir and ulonivirine in adults who had viral suppression on once daily bictegravir/emtricitabine/tenofovir alafenamide (brand name: Biktarvy).⁵ (NRTTIs are a new class of antiretroviral drugs currently under study for HIV treatment.)
Selected Study Results: The MK-8591-013 study was stopped early due to decreases in total lymphocyte and CD4 counts seen across islatravir trials. Available data was presented at IAS 2025 and showed that islatravir plus ulonivirine (given at three different dose levels) was effective in maintaining viral suppression through Week 24. The side effects of islatravir plus ulonivirine were similar to that of Biktarvy. Decreases in total lymphocyte and CD4 counts were seen in all islatravir plus ulonivirine study arms . Long-term follow-up showed that the declines in total lymphocyte and CD4 counts were generally reversible after participants had discontinued both study drugs.⁶

Study Names: MK-8591B-060; NCT06891066

Phase: 2b
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Australia, Puerto Rico, and Switzerland
Purpose: The purpose of this study is to evaluate the safety and efficacy of a switch to once-weekly islatravir and ulonivirine in adults with viral suppression on Biktarvy.²

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

Additional studies evaluating ulonivirine have been completed or are planned, including the following early-phase trials:

• MK-8507-001 and MK-8507-002: Two Phase 1 studies that evaluated the safety, tolerability , and pharmacokinetics of single and multiple doses of ulonivirine in adults without HIV. Investigators also looked at the potential for ulonivirine to interact with other drugs and whether ulonivirine needs to be taken with food. These studies have been completed, and results are available from Antimicrob Agents Chemother (2021).³
• MK-8507-015: A Phase 1 trial that evaluated the safety of multiple once-weekly doses of ulonivirine in adults without HIV. This study has been completed, and results are available from IAS 2025.⁷
• MK-8507-003 (NCT02174159): A Phase 1 study that assessed the safety, tolerability, pharmacokinetics, and antiviral activity of a single dose of ulonivirine monotherapy in treatment-naive adults with HIV. This study has been completed, and results are available from HIV Glasgow 2020 and the J Acquir Immune Defic Syndr (2021).⁸
• MK-8507-014 (NCT05093972): A Phase 1 study evaluating the safety and pharmacokinetics of a single dose of ulonivirine in adults without HIV with mild or moderate liver problems. See the ClinicalTrials.gov record for this study’s status.⁹

What side effects might ulonivirine cause?What side effects might ulonivirine cause?

What side effects might ulonivirine cause?

One goal of HIV research is to identify safe new drugs that have fewer side effects. In the IMAGINE-DR (MK-8591-013; NCT04564547) study discussed under the previous section, dosing of islatravir plus ulonivirine was stopped early due to declines in total lymphocyte and CD4 counts seen across all islatravir plus ulonivirine dose groups. Available safety data showed that islatravir plus ulonivirine had a comparable side effect profile to that of Biktarvy. Three participants discontinued islatravir plus ulonivirine because of drug-related side effects—diarrhea in one participant; abdominal pain, diarrhea, headache, nausea, oral herpes , and pain in another participant; and decreased appetite in a third participant. Long-term follow-up showed that total lymphocyte and CD4 counts trended back to baseline after participants discontinued islatravir and ulonivirine.^5,6

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

Where can I get more information about clinical trials studying ulonivirine?Where can I get more information about clinical trials studying ulonivirine?

Where can I get more information about clinical trials studying ulonivirine?

More information about ulonivirine-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 73505111, ulonivirine. Accessed November 24, 2025
2. Merck Sharp & Dohme LLC. A Phase 2b, randomized, active-controlled, open-label clinical study to evaluate a switch to islatravir (ISL) and ulonivirine (ULO) once weekly in adults with HIV-1 virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once daily. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 17, 2025. NLM Identifier: NCT06891066. Accessed November 24, 2025
3. Ankrom W, Jackson Rudd D, Schaeffer A, et al. Pharmacokinetic and safety profile of the novel HIV nonnucleoside reverse transcriptase inhibitor MK-8507 in adults without HIV. Antimicrob Agents Chemother. 65(12):e00935-21. doi:10.1128/AAC.00935-21. Accessed November 24, 2025
4. Diamond TL, Lai M-T, Feng M, et al. Resistance profile of MK-8507, a novel NNRTI suitable for weekly oral HIV treatment. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 6-11, 2021; Virtual. Accessed November 24, 2025
5. Merck Sharp & Dohme LLC. A Phase 2b, randomized, active-controlled, double-blind, dose-ranging clinical study to evaluate a switch to islatravir (ISL) and MK-8507 once-weekly in adults with HIV-1 virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once-daily. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 21, 2020. NLM Identifier: NCT04564547. Accessed November 24, 2025
6. Molina J-M, Ramgopal MN, Katlama C, et al. A double-blind, active-controlled, Phase 2b study to evaluate the efficacy and safety of ulonivirine in combination with islatravir in virologically suppressed adults living with HIV-1. International AIDS Society (IAS) Conference on HIV Science; July 13-17, 2025; Kigali, Rwanda. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2025. Accessed November 24, 2025
7. Nussbaum J, Liu Y, Pham M, et al. A double-blind, placebo-controlled, Phase 1 study to evaluate extended multiple dosing of ulonivirine (MK-8507) in adults without HIV. International AIDS Society (IAS) Conference on HIV Science; July 13-17, 2025; Kigali, Rwanda. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2025. Accessed November 24, 2025
8. Merck Sharp & Dohme LLC. A study to evaluate the safety, tolerability, pharmacokinetics and antiretroviral activity of MK-8507 in HIV-1 infected patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 24, 2014. NLM Identifier: NCT02174159. Accessed November 24, 2025
9. Merck Sharp & Dohme LLC. An open-label, single-dose clinical study to evaluate pharmacokinetics of MK-8507 in participants with mild or moderate hepatic impairment. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 18, 2021. NLM Identifier: NCT05093972. Accessed November 24, 2025