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 see whether switching to a once-weekly regimen of islatravir and ulonivirine is safe and can maintain control of viral load levels in adults with viral suppression on bictegravir/emtricitabine/tenofovir alafenamide (brand name: Biktarvy).⁵
Selected Study Results: The MK-8591-013 study was stopped early because of decreases in lymphocyte and CD4 counts seen across islatravir trials. Available results were presented at the International AIDS Society Conference on HIV Science (IAS 2025) and showed that islatravir plus ulonivirine worked to maintain viral suppression in participants through Week 24. The side effect profile of islatravir plus ulonivirine was similar to that of Biktarvy. Decreases in lymphocyte and CD4 counts were seen in all islatravir plus ulonivirine study arms. Long-term follow-up showed that the declines in lymphocyte and CD4 counts were generally reversible after participants stopped 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 see whether switching to once-weekly islatravir and ulonivirine is safe and can maintain control of viral load levels in adults with viral suppression on Biktarvy.⁷
Selected Study Results: Results were presented at the International AIDS Conference (AIDS 2026) and showed that once-weekly islatravir plus ulonivirine maintained viral suppression in participants through Week 24 and had similar efficacy to Biktarvy. No safety concerns were seen with islatravir plus ulonivirine, and the side effect profile of islatravir plus ulonivirine was comparable to Biktarvy.⁸

Study Names: MK-8591B-062; NCT07266831

Phase: 2/3
Status: This study is currently recruiting participants.
Locations: Multiple countries, including United States
Purpose: The purpose of the Phase 2 portion of this study is to evaluate once-weekly islatravir plus ulonivirine in adults who have never received HIV medicines before. Researchers will see 1) if islatravir plus ulonivirine is safe compared to Biktarvy and 2) if islatravir plus ulonivirine works as well as Biktarvy in controlling viral load levels.

The purpose of the Phase 3 portion of this study is to evaluate a once-weekly islatravir/ulonivirine fixed-dose combination tablet in adults who have never received HIV medicines before. Researchers will see 1) if the islatravir/ulonivirine fixed-dose combination tablet is safe compared to Biktarvy and 2) if the islatravir/ulonivirine fixed-dose combination tablet works as well as Biktarvy in controlling viral load levels.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. Some of these studies are described below.

• MK-8507-001 and MK-8507-002 were Phase 1 studies that looked at how the body handles ulonivirine and whether ulonivirine is safe and tolerable in adults without HIV. Researchers 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 was a Phase 1 trial that looked at the safety of once-weekly doses of ulonivirine in adults without HIV. This study has been completed, and results are available from IAS 2025.⁹
• MK-8507-003 (NCT02174159) was a Phase 1 study that evaluated how the body handles ulonivirine and whether ulonivirine is safe and tolerable in adults with HIV who have never received HIV medicines before. Researchers also looked at how well a single dose of ulonivirine monotherapy works to control viral load levels. This study has been completed, and results are available from the International Congress on Drug Therapy in HIV Infection (HIV Glasgow 2020) and the J Acquir Immune Defic Syndr (2021).¹⁰

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. The following side effects were observed in some of the studies of ulonivirine listed above.

IMAGINE-DR (MK-8591-013; NCT04564547)

In this Phase 2b study, treatment with islatravir plus ulonivirine was stopped early because of decreases in lymphocyte and CD4 counts seen across all islatravir clinical trials, including this trial. Available results showed that the side effect profile of islatravir plus ulonivirine was similar to that of Biktarvy. Three participants stopped taking 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 the decreases in lymphocyte and CD4 counts were generally reversible after participants stopped taking islatravir and ulonivirine.^5,6

MK-8591B-060 (NCT06891066)

In this Phase 2b study, the side effect profile of islatravir plus ulonivirine was comparable to that of Biktarvy. Ten participants receiving islatravir plus ulonivirine had drug-related side effects, all of which were mild or moderate. The only islatravir plus ulonivirine drug-related side effect occurring in more than one participant was dizziness. There were no drug-related serious side effects associated with islatravir plus ulonivirine. One participant stopped taking islatravir plus ulonivirine because of a drug-related skin reaction of moderate severity. Treatment with islatravir plus ulonivirine had no notable effect on lymphocyte and CD4 counts.⁸

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 October 15, 2026
2. Merck Sharp & Dohme LLC. A Phase 2/3, randomized, active-controlled, open-label (Phase 2) and double-blind (Phase 3) study to evaluate the antiretroviral activity, safety, and tolerability of islatravir (ISL) and ulonivirine (ULO) once weekly compared with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once daily in treatment-naïve adult participants living with HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 1, 2025. NLM Identifier: NCT07266831. Accessed October 15, 2026
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 October 15, 2026
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 October 15, 2026
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 October 15, 2026
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 October 15, 2026
7. 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 October 15, 2026
8. Luetkemeyer AF, Bloch M, Scribner A, et al. Randomized, active-controlled, phase 2b study evaluating efficacy and safety of switch to islatravir (ISL) 2 mg with ulonivirine (ULO) 200 mg once weekly in virologically suppressed adults living with HIV-1. International AIDS Conference; July 26-31, 2026; Rio, Brazil. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2026. Accessed October 15, 2026
9. 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 October 15, 2026
10. 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 October 15, 2026