Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People With HIV-1 (ISLEND-1)

A Phase 3, Randomized, Double-blind, Active-controlled Study to Evaluate a Switch to an Oral Weekly Islatravir/Lenacapavir Regimen in People With HIV-1 Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF)

The goal of this clinical study is to learn about the safety and efficacy of switching to once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard treatment of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels < 50 copies/mL) on B/F/TAF for ≥ 6 months prior to screening.

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

Study Overview

• Status: Active, not recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: ISL/LEN; Drug: PTM B/F/TAF; Drug: B/F/TAF; Drug: PTM ISL/LEN

• Study Type: Interventional
• Enrollment (Actual): 609
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1202
    • Fundacion Huesped
  • 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 Private Clinic
• Canada
  • Montreal, Canada, H2L 0B1
    • Clinique de médecine Urbaine du Quartier Latin
  • Montreal, Canada, H4A 3J1
    • McGill University Health Centr
  • Vancouver, Canada, V6Z 2T1
    • Spectrum Health
• France
  • Bourdeaux, France, 33075
    • CHU Bordeaux - Hôpital Saint André
  • Le Kremlin-Bicêtre, France, 94270
    • AP-HP-Hopital Bicétre
  • Marseile, France, 13009
    • Assistance Publique Hopitaux de Marseille - Hopital Sainte Marguerite
  • Nice, France, 6203
    • CHU Nice - Hopital Archet I
• Germany
  • Berlin, Germany, 10787
    • EPIMED GmbHGesellschaft fur klinische und epidemiologische Forschung in Berlin
  • Bonn, Germany, 53127
    • University Hospital Bonn, Medizinische und Poliklink I, Immunologische Studienambulanz
  • Cologne, Germany, 50924
    • Uniklinik Kéin, Innere Medizin |, Klinisches Studienzentrum Infektiologle, Clinical Trials Unit for Infectious Diseases(CTU-ID), ISZ Geb. 80
  • Essen, Germany, 45122
    • Universitatsmedizin Essen, Universitatsklinikum Essen, Klinik Dermatologie, Venerologie und Allergologie,, HPSTD-Ambulanz
  • Hamburg, Germany, 20146
    • ICH Study Center GmbH & Co.KG
• 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
• Puerto Rico
  • PR
    • San Juan, PR, Puerto Rico, 00909
      • Clinical Research Puerto Rico
    • San Juan, PR, Puerto Rico, 00935
      • University of Puerto Rico School of Medicine
• Spain
  • A Coruña, Spain, 15006
    • Complexo Hospitalario Universitario da Coruna
  • Barcelona, Spain, 08036
    • Hospital Clínic Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d' Hebron
  • Málaga, Spain, 29010
    • Hospital Universitario Regional de Malaga
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
  • Zurich, Switzerland, 8091
    • Universitaetsspital Zuerich
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Kaohsuing Medical University Hospital
  • Kaohsiung City, Taiwan, 81362
    • Kaohsuing Veterans General Hospital
  • New Taipei City, Taiwan, 22060
    • Far Eastern Memorial Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taoyuan City, Taiwan, 33004
    • Taoyuan General Hospital
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Hawthorn House, Birmingham Heartlands Hospital (University Hospitals Birmingham NHS Foundation Trust)
  • Brighton, United Kingdom, BN2 3EW
    • Clinical Research Facility (University Hospitals Sussex 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, WC1E 6JB
    • Mortimer Market Centre (Central and North West London NHS Foundation Trust)
  • London, United Kingdom, SW10 9TH
    • Clinical Research Facility, 1st Floor, St Stephen's Centre, Chelsea and Westminster Hospital (Chelsea and Westminster Hospital NHS Foundation Trust)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Pueblo Family Physicians
  • California
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Southern California
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group, Inc
    • Palm Springs, California, United States, 92262
      • BIOS Clinical Research
    • San Francisco, California, United States, 94102
      • Optimus Medical Group
  • Colorado
    • Denver, Colorado, United States, 80246
      • Vivent Health
    • Denver, Colorado, United States, 80262
      • University of Colorado- Anschutz Medical Campus - PPDS
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University
    • Washington D.C., District of Columbia, United States, 20009
      • Whitman-Walker Health
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • CAN Community Health
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami Gardens, Florida, United States, 33055
      • CAN Community Health
    • Oakland Park, Florida, United States, 33334
      • Midland Research Group, Inc.
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Pensacola, Florida, United States, 32504
      • AHF (AIDS Healthcare Foundation) - Pensacola Research
    • Sarasota, Florida, United States, 34237
      • CAN Community Health
    • Tampa, Florida, United States, 33607
      • St. Josephs Comprehensive Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Macon, Georgia, United States, 31201
      • Mercer University
    • Savannah, Georgia, United States, 31401
      • Chatham CARE Center
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02115
      • The Brigham and Women's Hospital, Inc.
    • Boston, Massachusetts, United States, 02129
      • Community Research Initiative
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Trinity Health
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • KC Care Health Center
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • ID Care
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • AXCES Research Group - Albuquerque
  • New York
    • Brooklyn, New York, United States, 11226
      • Brooklyn Clinical Research Center
    • Flushing, New York, United States, 11355
      • New York Presbyterian Hospital
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • The Bronx, New York, United States, 10461
      • Jacobi Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • CTRC University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28207
      • Atrium Health Infectious Disease Kenilworth
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Greenville, North Carolina, United States, 27858
      • Brody School of Medicine at East Carolina University Adult Specialty Care
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Health and Wellness
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health/USC
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants
    • 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
      • DCOL Center for Clinical Research
  • 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 (CARE-ID)
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit MD
    • Spokane, Washington, United States, 99202
      • MultiCare Institute for Research & Innovation
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison

Participation Criteria

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 week 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.
• Individuals are receiving B/F/TAF for ≥ 6 months prior to screening and willing to continue until Day 1.
• 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 > 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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blinded Phase: ISL/LEN + Placebo-to-Match (PTM) B/F/TAF; 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. Participants will also receive PTM B/F/TAF once daily from Day 1 up to Week 96.	Drug: ISL/LEN; Tablet administered orally; Drug: PTM B/F/TAF; Tablet administered orally
Experimental: Blinded Phase: PTM ISL/LEN + B/F/TAF; Participants will receive an initial dose of PTM ISL/LEN (Dose A), followed by once weekly PTM ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive B/F/TAF (50/200/25 mg) once daily up from Day 1 up to Week 96.	Drug: B/F/TAF; Tablet administered orally; Other Names: Biktarvy®; Drug: PTM ISL/LEN; Tablet administered orally
Experimental: Open- Label Extension (OLE) Phase; After the end of Blinded Phase at Week 96, if safety and efficacy of ISL/LEN are demonstrated following review of unblinded data, all participants will be given an option to enter the open-label extension phase to receive ISL/LEN 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 and PTM B/F/TAF during the blinded phase will continue to take ISL/LEN weekly. Participants receiving B/F/TAF and PTM ISL/LEN during the blinded 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	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-Defined Snapshot Algorithm	Week 96
Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Weeks 48 as Determined by the US FDA-Defined Snapshot Algorithm	Week 48
Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Weeks 96 as Determined by the US FDA-Defined Snapshot Algorithm	Week 96
Change From Baseline in Cluster of Differentiation 4 (CD4) T-Cell Count at Weeks 48	Week 48
Change From Baseline in CD4 T-Cell Count at Weeks 96	Week 96
Proportion of Participants Discontinuing ISL/LEN due to Treatment-Emergent Adverse Events (TEAEs)	Day 1 up to Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2024
• Primary Completion (Actual): April 17, 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 (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: bictegravir, emtricitabine, tenofovir alafenamide, drug combination
• Other Study ID Numbers: GS-US-563-5925; 2024-514046-37 (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