A Study of Islatravir (ISL) and Ulonivirine (ULO) Once Weekly (QW) in Virologically Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) (MK-8591B-060)

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

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 ISL+ULO, taken once a week, works compared to an existing treatment called BIC/FTC/TAF, which is taken every day. Investigators will check how many people still have a high level of the virus in their blood after 24 weeks. The investigators also want to understand if the new treatment, MK-8591B, is safe and how well people can handle it.

Study Overview

• Status: Active, not recruiting
• Conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection
• Intervention / Treatment: Drug: ISL; Drug: ULO; Drug: BIC/FTC/TAF

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Momentum Clinical Research - Darlinghurst ( Site 4260)
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincent's Hospital ( Site 4263)
  • Queensland
    • Fortitude Valley, Queensland, Australia, 4006
      • Momentum Clinical Research Fortitude Valley ( Site 4261)
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital ( Site 4264)
    • Prahran, Victoria, Australia, 3181
      • Prahran Market Clinic ( Site 4262)
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce Medical School Foundation Inc./CAIMED Center ( Site 4301)
  • San Juan, Puerto Rico, 00909
    • HOPE Clinical Research ( Site 4303)
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico ( Site 4300)
• Switzerland
  • Canton Ticino
    • Lugano, Canton Ticino, Switzerland, 6900
      • Ospedale Regionale di Lugano, Sede Civico-Servizio Malattie Infettive ( Site 4405)
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4031
      • University Hospital Basel-Infectiology ( Site 4402)
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3010
      • Inselspital Bern-Inselspital Infektiologie ( Site 4403)
  • Canton of Geneva
    • Geneva, Canton of Geneva, Switzerland, 1205
      • Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 4404)
• United States
  • California
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital and Trauma Center ( Site 4107)
    • West Hollywood, California, United States, 90046
      • Mills Clinical Research ( Site 4109)
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Medical Center ( Site 4106)
  • Florida
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center ( Site 4103)
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute ( Site 4111)
  • Georgia
    • Savannah, Georgia, United States, 31401
      • Chatham County Health Department - Chatham CARE Center ( Site 4116)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • KC CARE Health Center ( Site 4101)
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Regional Center for Infectious Diseases ( Site 4115)
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research ( Site 4100)
    • Dallas, Texas, United States, 75208
      • Prism Health North Texas, Oak Cliff Health Center ( Site 4114)
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research ( Site 4112)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion:

The main inclusion criteria include but are not limited to the following:

- Has been receiving Bictegravir/Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF) therapy with documented viral suppression [Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL] for ≥6 months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen.

Exclusion:

The main exclusion criteria include but are not limited to the following:

• 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) coinfection.
• Has hepatitis B virus (HBV) coinfection.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ISL + ULO in Group 1; 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.	Drug: ISL; ISL 1mg oral capsule will be administered as 2mg orally (each capsule 1mg) as part of ISL and ULO combination to group 1 participants for 96 weeks and for group 2 participants in part 2 of the study from 49 to 96 weeks.; Other Names: MK-8591; Islatravir; Drug: ULO; ULO 100mg oral tablet will be administered as 200mg (2 tablets) orally as part of ISL and ULO combination to group 1 participants for 96 weeks and for group 2 participants in part 2 of the study from 49 to 96 weeks.; Other Names: MK-8507; Ulonivirine.
Active Comparator: BIC/FTC/TAF in Group 2; In part 1 of the study, participants will receive BIC 50mg/FTC 200mg/TAF 25mg orally once daily (QD) for 48 weeks.	Drug: BIC/FTC/TAF; BIC 50mg oral tablet/FTC 200mg oral tablet/TAF 25 mg oral tablet administered orally to group 2 participants for 48 weeks in part 1 of the study.; Other Names: BIKTARVY®
Experimental: ISL + ULO in Group 2; 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.	Drug: ISL; ISL 1mg oral capsule will be administered as 2mg orally (each capsule 1mg) as part of ISL and ULO combination to group 1 participants for 96 weeks and for group 2 participants in part 2 of the study from 49 to 96 weeks.; Other Names: MK-8591; Islatravir; Drug: ULO; ULO 100mg oral tablet will be administered as 200mg (2 tablets) orally as part of ISL and ULO combination to group 1 participants for 96 weeks and for group 2 participants in part 2 of the study from 49 to 96 weeks.; Other Names: MK-8507; Ulonivirine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA ≥50 copies/mL at Week 24	Plasma HIV-1 ribonucleic acid (RNA) quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay. Percentage of participants with HIV-1 RNA ≥50 copies/mL will be reported at week 24.	Week 24
Percentage of Participants who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience an AE will be reported.	Up to ~ 96 weeks
Percentage of Participants Discontinuing Study Treatment due to AEs	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinue study treatment due to an AE will be reported.	Up to ~ 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA ≥50 copies/mL at Week 48	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay. Percentage of participants with HIV-1 RNA ≥50 copies/mL will be reported at week 48.	Week 48
Percentage of Participants With HIV-1 RNA <50 copies/mL at Week 24	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA <50 copies/mL will be reported at week 24.	Week 24
Percentage of Participants With HIV-1 RNA <50 copies/mL at Week 48	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA <50 copies/mL will be reported at week 48.	Week 48
Percentage of Participants With HIV-1 RNA <200 copies/mL at Week 24	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA <200 copies/mL will be reported at week 24.	Week 24
Percentage of Participants With HIV-1 RNA <200 copies/mL at Week 48	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA <200 copies/mL will be reported at week 48.	Week 48
Percentage of Participants With HIV-1 RNA ≥50 copies/mL at Week 96	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA ≥50 copies/mL will be reported at week 96.	Week 96
Percentage of Participants With HIV-1 RNA <50 copies/mL at Week 96	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA <50 copies/mL will be reported at week 96.	Week 96
Percentage of Participants With HIV-1 RNA <200 copies/mL at Week 96	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA <200 copies/mL will be reported at week 96.	Week 96
Mean Change From Baseline in CD4+ T-cell Count at Week 24	The mean change from baseline in CD4+ T-cell count will be calculated at each applicable time point at which CD4+ T-cell count is collected with primary interest at 24 weeks. Blood samples are taken for this purpose. Baseline measurements are defined as the Day 1 value for each participant.	Week 24
Mean Change From Baseline in CD4+ T-cell Count at Week 48	The mean change from baseline in CD4+ T-cell count will be calculated at each applicable time point at which CD4+ T-cell count is collected with primary interest at 48 weeks. Blood samples are taken for this purpose. Baseline measurements are defined as the Day 1 value for each participant.	Week 48
Mean Change From Baseline in CD4+ T-cell Count at Week 96	The mean change from baseline in CD4+ T-cell count will be calculated at each applicable time point at which CD4+ T-cell count is collected with primary interest at 96 weeks. Blood samples are taken for this purpose. Baseline measurements are defined as the Day 1 value for each participant.	Week 96
Percentage of Participants With Development of Viral Drug Resistance to any Component of Study Intervention at Week 24	Antiviral drug resistance is the reduced susceptibility of the virus to the study intervention. Participants with HIV-1 RNA ≥400 copies/mL will be included in the resistance analyses. Participants who have test results showing signs of viral resistance will also be included for analysis, irrespective of the viral load. Percentage of participants in each treatment group who have evidence of resistance-associated substitutions will be analyzed at week 24.	Week 24
Percentage of Participants With Development of Viral Drug Resistance to any Component of Study Intervention at Week 48	Antiviral drug resistance is the reduced susceptibility of the virus to the study intervention. Participants with HIV-1 RNA ≥400 copies/mL will be included in the resistance analyses. Participants who have test results showing signs of viral resistance will also be included for analysis, irrespective of the viral load. Percentage of participants in each treatment group who have evidence of resistance-associated substitutions will be analyzed at week 48.	Week 48
Percentage of Participants With Development of Viral Drug Resistance to any Component of Study Intervention at Week 96	Antiviral drug resistance is the reduced susceptibility of the virus to the study intervention. Participants with HIV-1 RNA ≥400 copies/mL will be included in the resistance analyses. Participants who have test results showing signs of viral resistance will also be included for analysis, irrespective of the viral load. Percentage of participants in each treatment group who have evidence of resistance-associated substitutions will be analyzed at week 96.	Week 96

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2025
• Primary Completion (Estimated): August 10, 2027
• Study Completion (Estimated): September 30, 2031

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: March 17, 2025
• First Posted (Actual): March 24, 2025

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: HIV-1
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Infections; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-Retroviral Agents; bictegravir, emtricitabine, tenofovir alafenamide, drug combination; islatravir; ulonivirine
• Other Study ID Numbers: 8591B-060; MK-8591B-060 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No