ISL + ULO for HIV

Not currently recruiting at 24 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: BIC/FTC/TAF

Must not be taking: Islatravir, Ulonivirine

Disqualifiers: HIV-2, Active AIDS, HCV, HBV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find a better treatment for people with HIV-1 by testing a new medication, Islatravir (ISL) and Ulonivirine (ULO), taken once a week. Researchers seek to determine if this weekly treatment maintains low virus levels in the blood over 24 weeks as effectively as the current daily medication, BIC/FTC/TAF. The trial will also assess whether participants can tolerate the new treatment without major side effects. Individuals who have successfully managed their HIV-1 with daily BIC/FTC/TAF and have not experienced treatment failures may be suitable candidates for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you have been on the BIC/FTC/TAF treatment with controlled HIV-1 levels for at least 6 months before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of Islatravir (ISL) and Ulonivirine (ULO) is generally well-tolerated. In studies, most participants did not discontinue treatment due to side effects. Safety results over 144 weeks revealed that only a few individuals stopped because of side effects.

However, some side effects did occur. About 76.9% of those taking ISL and ULO reported side effects. These were not severe but were more common compared to the existing treatment, where 67.5% of participants experienced similar issues.

This combination remains under study, and while early data is promising, researchers continue to monitor its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for HIV?

Researchers are excited about Islatravir (ISL) and Ulonivirine (ULO) because these treatments could simplify HIV management. Unlike standard daily therapies like BIC/FTC/TAF, ISL and ULO offer a once-weekly oral regimen, which might improve adherence and quality of life for patients. Additionally, Islatravir uses a novel mechanism as a nucleoside reverse transcriptase translocation inhibitor, potentially providing better viral suppression. This innovative approach could offer a more convenient and effective option for people living with HIV.

What evidence suggests that this trial's treatments could be effective for HIV?

Research has shown that the combination of islatravir and ulonivirine, which participants in this trial may receive, holds promise for treating HIV-1. Studies have found that taking this combination once a week effectively controls the virus for many patients over 24 weeks. Specifically, all participants with available data maintained low levels of the virus in their blood, suggesting the treatment effectively keeps the virus under control. The once-a-week dosing also offers the added benefit of making it easier for people to adhere to their treatment plan. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with HIV-1 who have been successfully treated and virus-suppressed using BIC/FTC/TAF therapy for at least 6 months without any past treatment failures. Participants must have maintained a viral load under 50 copies/mL to qualify.

Inclusion Criteria

The main

I've been on BIC/FTC/TAF for HIV with successful control for over 6 months without past treatment failures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive either ISL + ULO once weekly or BIC/FTC/TAF once daily for 48 weeks

48 weeks

Treatment Part 2

Participants continue or switch to ISL + ULO once weekly for an additional 48 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Islatravir
• Ulonivirine

Trial Overview The study compares a new once-weekly HIV-1 treatment regimen (ISL+ULO) against the standard daily regimen (BIC/FTC/TAF). The goal is to see if ISL+ULO maintains virus suppression after 24 weeks and assess its safety and tolerability.

How Is the Trial Designed?

Group I: ISL + ULO in Group 2 Experimental Treatment 2 Interventions

In part 2 of the study, participants previously on BIC/FTC/TAF (for the 1st 48 weeks, or part 1) will switch to ISL + ULO, to week 96.

Group II: ISL + ULO in Group 1 Experimental Treatment 2 Interventions

In part 1 of the study, participants will receive ISL 2mg + ULO 200mg orally once a week (QW) for 48 weeks. In part 2 (2nd 48 weeks), participants will continue to receive ISL 2mg + ULO 200mg once a week till week 96.

Group III: BIC/FTC/TAF in Group 2 Active Control 1 Intervention

In part 1 of the study, participants will receive BIC 50mg/FTC 200mg/TAF 25mg orally once daily (QD) for 48 weeks.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Islatravir, a novel nucleoside analog for HIV treatment and prevention, demonstrated potent antiviral activity with a long intracellular half-life, achieving therapeutic concentrations in both plasma and tissue after daily administration for up to 6 weeks.

The study involving 36 adults showed that islatravir was generally well tolerated at doses up to 5 mg, with effective levels of its active form (ISL-TP) reached after just one dose, indicating its potential for effective HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Once-Daily Multiple-Dose Administration of Islatravir in Adults Without HIV. Matthews, RP., Jackson Rudd, D., Zhang, S., et al.[2023]

Islatravir, a new treatment for HIV-1, was found to be generally well tolerated in a phase 1b trial with 30 treatment-naive adults, showing that it can significantly reduce HIV-1 RNA levels by more than 1.0 log after just 7 days, even at low doses of 0.5 mg.

The study demonstrated that islatravir has a long intracellular half-life of 78.5-128.0 hours, which may contribute to its prolonged effects against the virus, and no serious adverse events or signs of viral resistance were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial. Schürmann, D., Rudd, DJ., Zhang, S., et al.[2020]

In a phase 2b trial involving 121 treatment-naive participants, islatravir combined with doravirine maintained HIV-1 RNA levels below 50 copies per milliliter in 81.1% of participants over 96 weeks, demonstrating its efficacy in viral suppression.

The safety profile of islatravir was favorable, with only 7.8% of participants experiencing drug-related adverse events, compared to 22.6% in the DOR/3TC/TDF group, indicating better tolerability for the islatravir regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Efficacy and Safety of Oral Islatravir Once Daily in Combination With Doravirine Through 96 Weeks for Treatment-Naive Adults With HIV-1 Infection Receiving Initial Treatment With Islatravir, Doravirine, and Lamivudine. Molina, JM., Yazdanpanah, Y., Afani Saud, A., et al.[2023]

Islatravir (ISL) is a novel long-acting reverse transcriptase translocation inhibitor that has shown strong antiviral activity in both daily and weekly dosing regimens for HIV-1 treatment, achieving high levels of virologic suppression in clinical trials.

In preclinical studies, ISL demonstrated effectiveness as a once-weekly pre-exposure prophylaxis (PrEP) against SHIV infection in rhesus macaques, and recent data suggest the potential for a once-yearly implantable formulation for HIV-1 prevention in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islatravir for the treatment and prevention of infection with the human immunodeficiency virus type 1. Markowitz, M., Grobler, JA.[2021]

Citations

1. merck.com merck.com/news/merck-to-present-new-data-highlighting-research-advancements-across-its-hiv-prevention-and-treatment-pipeline-at-ias-2025/

Merck to Present New Data Highlighting Research ... Merck will share new scientific findings from its HIV clinical development programs, including Phase 2 data on the safety and pharmacokinetics of MK-8527.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06891066

NCT06891066 | A Study of Islatravir (ISL) and Ulonivirine ... Investigators are trying to find better treatments for people with HIV-1. In this clinical study, investigators want to see how well a new treatment called ...

3. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/drugs/islatravir/patient

Islatravir Patient Drug Record | NIH Available data was presented at IAS 2025 and showed that islatravir plus ulonivirine (given at three different dose levels) was effective in maintaining viral ...

4. eatg.org eatg.org/hiv-news/once-weekly-oral-art-with-ulonivirine-plus-islatravir-24-week-phase-2-results/

Once-weekly oral ART with ulonivirine plus islatravir Once-weekly oral ART with ulonivirine plus islatravir: 24-week phase 2 results · IAS 2025 · Long-Acting Antiretrovirals.

5. medpagetoday.com medpagetoday.com/meetingcoverage/ias/116525

Investigational Once-Weekly ART Combo Maintained Viral ... Among participants with available data, all remained virologically suppressed with islatravir 20 mg and ulonivirine at dosages of 100 mg, 200 mg ...

6. humanforschung-schweiz.ch humanforschung-schweiz.ch/en/trial-search/study-detail/66790/translate/en/?cHash=ef9d58dd74bc4220b2ed33d476a0e540

Clinical Study of Islatravir (ISL) and Ulonivirine (ULO) in ... The main objective of this study is to investigate and evaluate the safety, tolerability, and efficacy of Islatravir (ISL) and Ulonivirine (ULO) ...