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Once-weekly islatravir plus ulonivirine for people with untreated HIV-1

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

Phase2; Phase3 Interventional Merck Sharp & Dohme LLC · NCT07266831

This trial tests whether a once-weekly oral combination of islatravir and ulonivirine can control HIV-1 in people who have never taken antiretroviral therapy.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment570 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Locations53 sites (Los Angeles, California and 52 other locations)
Trial IDNCT07266831 on ClinicalTrials.gov

What this trial studies

This phase 2/3 study enrolls ART‑naïve adults with HIV-1 and compares a once-weekly oral regimen of islatravir plus ulonivirine to a standard once-daily antiretroviral regimen (bictegravir/emtricitabine/tenofovir alafenamide). Participants are randomized and receive matching placebos as needed to maintain blinding. Primary goals include measuring viral suppression rates and characterizing safety and tolerability over time. The trial excludes people with HIV-2, active hepatitis B or C, recent malignancy, or AIDS-defining opportunistic infections.

Who should consider this trial

Good fit: Ideal candidates are adults with HIV-1 who are antiretroviral‑naïve with plasma HIV-1 RNA ≥500 copies/mL (and for phase 2 a CD4+ count ≥200 cells/mm3) and who do not have active hepatitis B/C or AIDS‑defining infections.

Not a fit: People with HIV-2, active hepatitis B or C, recent malignancy, AIDS-defining opportunistic infections, prior ART exposure, or very low CD4 counts are unlikely to benefit from or be eligible for this trial.

Why it matters

Potential benefit: If successful, the regimen could offer effective viral control with once-weekly dosing, which may improve convenience and adherence compared with daily therapy.

How similar studies have performed: Prior studies of islatravir and of long-acting antiretroviral approaches have shown strong antiviral activity, though long-acting combinations remain relatively new and the overall safety and durability profile continues to be defined.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Phase 2: Is human immunodeficiency virus type 1 (HIV-1) positive with Plasma HIV-1 ribonucleic acid (RNA) ≥500 and ≤100,000 copies/mL.
* Phase 3: Is HIV-1 positive with Plasma HIV-1 RNA ≥500 copies/mL.
* Phase 2: Has cluster of differentiation 4-positive (CD4+) T-cell count ≥200 cells/mm\^3.
* Is naïve to antiretroviral therapy (ART), defined as having received no prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection.

Exclusion Criteria:

* Has human immunodeficiency virus type 2 (HIV-2) infection.
* Has a diagnosis of an active acquired immune deficiency syndrome (AIDS)-defining opportunistic infection.
* Has active hepatitis C virus (HCV) or active hepatitis B virus (HBV) infection.
* Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or in situ anal cancer, or cutaneous Kaposi's sarcoma.
* Has prior exposure to islatravir (ISL) or ulonivirine (ULO) for any duration any time prior to Day 1.

Where this trial is running

Los Angeles, California and 52 other locations

+3 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Human Immunodeficiency Virus Type 1 Infection
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.