Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1 (ISLEND-2)

November 12, 2025 updated by: Gilead Sciences

A Phase 3, Randomized, Open-Label, Active-Controlled Study to Evaluate a Switch to an Oral Weekly Islatravir/Lenacapavir Regimen in People With HIV-1 Who Are Virologically Suppressed on Standard of Care

The goal of this clinical study is to learn more about the safety and efficacy of switching to a once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard of care treatment in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels < 50 copies/mL) on a stable standard of care regimen for ≥ 6 months prior to screening. The standard of care includes 2 or 3 medicines, antiretroviral agents (ARVs).

The primary objective of the study is to evaluate the efficacy of switching to oral weekly ISL/LEN tablet regimen versus continuing standard of care in virologically suppressed PWH at Week 48.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

600

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, 1202
        • Fundación Huésped
      • Buenos Aires, Argentina, 1072
        • Hospital General de Agudos Dr. J.M. Ramos Mejia
      • Buenos Aires, Argentina, 1425
        • Helios Salud S.A.
  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • St Vincent's Hospital
      • Darlinghurst, New South Wales, Australia, 2010
        • East Sydney Doctors
      • Surry Hills, New South Wales, Australia, 2010
        • Taylor Square Private Clinic
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Health
      • South Yarra, Victoria, Australia, 3141
        • Prahran Market Clinic
  • Germany
      • Cologne, Germany, 50674
        • Dr. Scholten & Schneeweiß GbR
      • Hanover, Germany, 30625
        • University Hospital Hannover, Department for Rheumatology and Immunology
      • Mannheim, Germany, 68167
        • Mannheimer Onkologie Praxis
      • München, Germany, 80337
        • MVZ München am Goetheplatz, MUC Research GmbH
  • Japan
      • Chiba, Japan
        • Chiba University Hospital
      • Nagoya, Japan, 460-0001
        • National Hospital Organization Nagoya Medical Center
      • Okinawa, Japan
        • University of the Ryukyus Hospital
      • Osaka, Japan, 534-0021
        • Osaka City General Hospital
      • Osaka Fu, Japan, 540-0006
        • National Hospital Organization Osaka National Hospital
      • Tokyo, Japan, 160-0023
        • Tokyo Medical University Hospital
      • Tokyo, Japan, 162-8655,
        • Japan Institute for Health Security National Center for Global Health and Medicine
  • Netherlands
      • Amsterdam, Netherlands, 1105 az
        • Amsterdam UMC, Iocation AMC
      • Leiden, Netherlands, 2333 ZA
        • Leiden University Medical Center (LUMC)
  • Poland
      • Szczecin, Poland, 71-455
        • Samodzielny Publiczny Wojewodzig Szpital Zespolony Poradnia Nabytych Niedoborow Immunologicznych
      • Wroclaw, Poland, 50-136
        • Wroclawskie Centrum Zorowia Samodzielny Publiczn Zaklad Opieki Zdrowotnej Sp Zoo Osrodek Profilaktyczno-Leczniczy Chorob Zakaznych I Terapi Uzaleznien
  • Puerto Rico
      • San Juan, Puerto Rico, 00936-5067
        • Maternal Infant Studies Center(CEMI)
    • PR
      • San Juan, PR, Puerto Rico, 00909
        • Hope Clinical Research
  • South Africa
      • Cape Town, South Africa, 7925
        • Desmond Tutu Health Foundation, Clinical Trials Unit
      • Soweto, South Africa, 2013
        • Perinatal HIV Research Unit
  • Spain
      • Barcelona, Spain, 08916
        • Hospital Germans Trias i Pujol
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio
  • Switzerland
      • Bern, Switzerland, 3010
        • Inselspital, Freiburgstrasse 20. Bern
      • Geneva, Switzerland, 1205
        • Hôpitaux Universitaires de Genève
      • Lausanne, Switzerland, 1011
        • Centre hospitalier universitaire vaudois
  • Taiwan
      • Kaohsiung City, Taiwan, 81362
        • Kaohsiung Veterans General Hospital
      • Kaohsiung City, Taiwan, 80756
        • Kaohsiung Medical University Hospital
      • New Taipei City, Taiwan, 22060
        • Far Eastern Memorial Hospital
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
      • Taoyuan, Taiwan, 33004
        • Taoyuan General Hospital
  • Thailand
      • Bangkok, Thailand, 10700
        • Siriraj Hospital
      • Bangkok, Thailand, 10330
        • The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research
      • Chiang Mai, Thailand, 50200
        • Chiang Mai University
      • Khon Kaen, Thailand, 40002
        • Khon Kaen University
      • Nonthaburi, Thailand, 11000
        • Bamrasnaradura Infectious Disease Institute
      • Pathumwan, Thailand, 10330
        • Institute of HIV Research and Innovation (IHRI)
  • United Kingdom
      • Brighton, United Kingdom, BN2 3EW
        • Clinical Research Facility -University Hospitals Sussex NHS Foundation Trust
      • Great Maze Pond, United Kingdom, SE1 3RR
        • Harrison Wing Research Unit, Southwark Wing, Guy's Hospital (Guy's & St. Thomas' NHS Foundation Trust)
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital (Royal Free London NHS Foundation Trust)
      • London, United Kingdom, E1 1BB.
        • Grahame Hayton Unit, Ambrose King Centre, Royal London Hospital (Barts Health NHS Trust)
      • London, United Kingdom, SE5 9RJ
        • Caldecot Centre, King's College Hospital (King's College Hospital NHS Foundation Trust)
      • London, United Kingdom, WC1E 6JB
        • Mortimer Market Centre (Central and North West London NHS Foundation Trust)
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham(UAB) 1917 Research Clinic
    • Arizona
      • Phoenix, Arizona, United States, 85015
        • Pueblo Family Physicians
    • California
      • Los Angeles, California, United States, 90036
        • Ruane Clinical Research Group
      • Los Angeles, California, United States, 90027
        • Vv-Tmf-5366229
      • Palm Springs, California, United States, 92262
        • BIOS Clinical Research
    • Colorado
      • Denver, Colorado, United States, 80246
        • Vivent Health
      • Denver, Colorado, United States, 80262
        • University of Colorado Clinical and Translational Research Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University; School of Medicine; AIDS Program
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown University Medical Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • AIDS Healthcare Foundation - Northpoint
      • Ft. Pierce, Florida, United States, 34982
        • Midway Immunology and Research Center
      • Miami Gardens, Florida, United States, 33055
        • CAN Community Health
      • Orlando, Florida, United States, 32803
        • Orlando Immunology Center
      • Pensacola, Florida, United States, 32503
        • AHF Pensacola
      • Sarasota, Florida, United States, 34237
        • CAN Community Health
      • Tampa, Florida, United States, 33607
        • BayCare Health System, Inc./St. Joseph's Hospital
      • West Palm Beach, Florida, United States, 33401
        • Triple O Research Institute, P.A.
    • Georgia
      • Decatur, Georgia, United States, 30033
        • Metro Infectious Disease Consultants, P.L.L.C.
      • Macon, Georgia, United States, 31201
        • Mercer University, Department of Internal Medicine
      • Savannah, Georgia, United States, 31401
        • Chatham County Health Department
    • Illinois
      • Chicago, Illinois, United States, 60613
        • Howard Brown Health Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana CTSI Clinical Research Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Boston, Massachusetts, United States, 02115
        • Brigham and Womens's Hospital
      • Boston, Massachusetts, United States, 02129
        • Community Research Initiative of New England d/b/a Community Resource Initiative (CRI)
    • Michigan
      • Berkley, Michigan, United States, 48072
        • Be Well Medical Center
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health
      • Grand Rapids, Michigan, United States, 49503
        • Trinity Health Michigan d/b/a Trinity Health Grand Rapids Hospital
    • New Jersey
      • Hillsborough, New Jersey, United States, 08844
        • ID CARE
      • Newark, New Jersey, United States, 07102
        • Saint Michael's Medical Center
    • New Mexico
      • Santa Fe, New Mexico, United States, 87505
        • AXCES Research Group, LLC
    • New York
      • Flushing, New York, United States, 11355
        • NewYork-Presbyterian Queens
      • Manhasset, New York, United States, 11030
        • Northwell Health/Division of Infectious Diseases
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • The Bronx, New York, United States, 10461
        • Jacobi Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Health System(DUHS)
      • Greenville, North Carolina, United States, 27834
        • ECU Health Leo Jenkins Cancer Building
      • Huntersville, North Carolina, United States, 28078
        • Rosedale Health and Wellness
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati College of Medicine
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Midlands - Clinical Research Unit
    • Texas
      • Austin, Texas, United States, 78705
        • Central Texas Clinical Research
      • Dallas, Texas, United States, 75246
        • North Texas Infectious Diseases Consultants, PA
      • El Paso, Texas, United States, 79902
        • AXCES Research Group, LLC
      • Fort Worth, Texas, United States, 76104
        • Texas Centers for Infectious Disease Associates
      • Houston, Texas, United States, 77098
        • The Crofoot Research Center, INC.
      • Longview, Texas, United States, 75605
        • Clinical Alliance for Research& Education - Infectious Diseases, LLC (CARE-ID)
    • Utah
      • Salt Lake City, Utah, United States, 84102
        • AXCES Research Group, LLC
    • Virginia
      • Annandale, Virginia, United States, 22003
        • Clinical Alliance for Research& Education - Infectious Diseases, LLC
    • Washington
      • Spokane, Washington, United States, 99202
        • MultiCare Rockwood Main Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • HIV-1 RNA < 50 copies/mL for ≥ 6 months before screening, as documented by:

    1. One HIV-1 RNA < 50 copies/mL immediately preceding the 24 weeks period prior to screening.
    2. Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be < 50 copies/mL.
    3. During the 6 to 12 months period prior to screening, transient detectable viremia ≥ 50 copies/mL is acceptable ("blip") as long as it is not confirmed on 2 consecutive visits.
  • Plasma HIV-1 RNA levels < 50 copies/mL at screening.
  • Are receiving guideline-recommended standard of care treatment such as International Antiviral Society (IAS), Department of Health and Human Services (DHHS), European AIDS Clinical Society (EACS) consisting of 2 or 3 ARVs for ≥ 6 months prior to screening and willing to continue until Day 1. Individuals in Treatment Group 2 must also be willing to continue their standard of care through at least Week 96.
  • Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception.

Key Exclusion Criteria:

  • Prior virologic failure.
  • Prior use of, or exposure to, ISL or LEN.
  • Active, serious infections requiring parenteral therapy within 30 days before randomization.
  • Active tuberculosis infection.
  • Acute hepatitis within 30 days before randomization.

  • Hepatitis B virus (HBV) infection, as determined below at the screening visit:

    1. positive HBV surface antigen OR
    2. positive HBV core antibody and negative HBV surface antibody. Note: individuals found to be susceptible to HBV infection (eg negative hepatitis B surface antibody at the screening visit, regardless of prior HBV vaccination history) should be recommended to receive HBV vaccination.
  • Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Note: individuals with prior/inactive HCV infection (defined as undetectable HCV RNA) may be enrolled.

  • Any of the following laboratory values at screening:

    1. Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
    2. Alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN)
    3. Direct bilirubin > 1.5 x ULN
    4. Platelets < 50,000/μL
    5. Hemoglobin < 8.0 g/dL

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ISL/LEN
Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96.
Drug: ISL/LEN
Tablet administered orally
Active Comparator: Standard of Care Treatment

Participants will continue standard of care treatment with 2-3 ARVs up to Week 96:

  • Integrase Strand Transfer Inhibitor (INSTI) class: INSTI combined with 1 or 2 nucleoside reverse transcriptase inhibitors (NRTIs; bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®), dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC), DTG+ TAF or TDF (TXF)/emtricitabine (FTC; Emtriva®), DTG/tenofovir disoproxil fumarate (TDF; Viread®)/3TC, DTG/3TC, raltegravir (RAL) + TXF/FTC, RAL+TDF/3TC, elvitegravir (EVG; Vitekta®)/cobicistat (c; Tybost®)/TXF/FTC), or
  • PI class: Boosted protease inhibitor (PI) combined with 2 NRTIs (darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF; coformulated), boosted darunavir (DRV)+TXF/FTC, boosted DRV+TDF/3TC), or
  • NNRTI class: Nonnucleoside reverse transcriptase inhibitor (NNRTI) combined with 2 NRTIs (doravirine (DOR)/TDF/3TC, DOR+TXF/FTC, DOR+TDF/3TC, rilpivirine (RPV)/TXF/FTC, RPV+TXF/FTC, RPV+TDF/3TC)
Drug: ISL/LEN
Tablet administered orally
Drug: Antiretroviral Combinations
2 or 3 antiretrovirals (ARVs) administered as defined by the investigator, according to the prescribing information.
Experimental: Extension Phase

At the end of randomized treatment visit, if safety and efficacy of ISL/LEN are demonstrated following review of randomized data, participants will be given the option to receive ISL/LEN tablets in an extension phase until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first.

Participants receiving ISL/LEN during the randomized phase will continue to take ISL/LEN weekly.

Participants receiving standard of care during the randomized phase will take an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards.
Drug: ISL/LEN
Tablet administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm
Time Frame: Week 48
Week 48

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
Time Frame: Week 48
Week 48
Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm
Time Frame: Week 96
Week 96
Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm
Time Frame: Week 96
Week 96
Change from Baseline in clusters of differentiation 4 (CD4) T-Cell Count at Week 48
Time Frame: Baseline, Week 48
Baseline, Week 48
Change from Baseline in CD4 T-Cell Count at Week 96
Time Frame: Baseline, Week 96
Baseline, Week 96
Proportion of Participants Discontinuing ISL/LEN due to Treatment-Emergent Adverse Events (TEAEs)
Time Frame: First dose date up to Week 96
First dose date up to Week 96

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2024

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

August 1, 2030

Study Registration Dates

First Submitted

October 4, 2024

First Submitted That Met QC Criteria

October 4, 2024

First Posted (Actual)

October 8, 2024

Study Record Updates

Last Update Posted (Estimated)

November 14, 2025

Last Update Submitted That Met QC Criteria

November 12, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-563-5926
  • 2024-514047-28 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV-1-Infection

Clinical Trials on ISL/LEN

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Netherlands

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe