Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With Biktarvy (ARTISTRY-2)

Phase 3 Double-blind Multicenter Randomized Active-Controlled Study to Evaluate the Safety and Efficacy of Bictegravir/Lenacapavir Versus Biktarvy® (Bictegravir/Emtricitabine/Tenofovir Alafenamide) in Virologically Suppressed People With HIV-1

The goal of this clinical study is to learn more about the effects of switching to the study drugs, bictegravir (BIC)/lenacapavir (LEN), fixed-dose combination (FDC) versus current therapy bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) FDC in people living with HIV-1 (PWH) who are successfully treated with B/F/TAF (virologically suppressed).

The primary objective of this study is to evaluate the efficacy of switching to BIC/LEN (75/50 mg) FDC tablets versus continuing on B/F/TAF (50/200/25 mg) FDC tablets in virologically suppressed PWH.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Lenacapavir; Drug: Bictegravir/Lenacapavir (BIC/LEN) FDC; Drug: Placebo to match B/F/TAF; Drug: B/F/TAF; Drug: Placebo to match BIC/LEN FDC; Drug: Placebo to match Lenacapavir

• Study Type: Interventional
• Enrollment (Actual): 577
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1141ACG
    • Helios Salud S.A.
  • Buenos Aires, Argentina, C1202ABB
    • Fundacion Huesped
  • Santa Fe, Argentina, S2000PBJ,
    • Instituto CAICI SRL
• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2011
      • Taylor Square Private Clinic
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital(Alfred Health)
    • South Yarra, Victoria, Australia, 3141
      • Prahran Market Clinic
• Canada
  • Decarie Montreal, Canada, H4A 3J1
    • Chronic Viral Illness Service/McGill University Health Centre (MUHC)
  • Montreal, Canada, H2L 4P9
    • Clinique Médicale l'Actuel
  • Ottawa, Canada, K1H 8L6
    • The Ottawa Hospital - General Campus
  • Regina, Canada, S4P 0W5
    • Regina General Hospital
  • Vancouver, Canada, V6Z1Y6
    • St. Paul's Hospital, John Ruedy Clinic-Immunodeficiency Clinic (JRC-IDC)
  • Victoria, Canada, V8W 1M8
    • Cool Aid Community Health Centre
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Instituto Dominicano de Estudios Virologicos - IDEV
• Germany
  • Aachen, Germany, 52062
    • Praxis Dr. Knechten
  • Berlin, Germany, 10117
    • Novopraxis Berlin
  • Cologne, Germany, 50668
    • Praxis am Ebertplatz
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Frankfurt
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg Eppendorf
  • Munich, Germany, 80336
    • LMU Klinikum der Universität
  • München, Germany, 81675
    • Klinikum rechts der Isar der Technischen Universitaet Muenchen
• Italy
  • Brescia, Italy, 25123
    • ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN
  • Foggia, Italy, 71122
    • Azienda Ospedaliero Universitaria Ospedali Riuniti (Policlinico di Foggia)
  • Milan, Italy, 20127
    • IRCCS Ospedale San Raffaele
  • Monza, Italy, 20090
    • Fondazione IRCCS San Gerardo dei Tintori - ASST di Monza - A. O. San Gerardo
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo di Pavia
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A Gemelli-Rome
  • Roma, Italy, 00149
    • Istituto Nazionale Malattie Infettive Lazzaro Spallanzani IRCCS
• Japan
  • Aichi, Japan, 460-0001
    • National Hospital Organization Nagoya Medical Center
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka National Hospital
  • Tokyo, Japan, 162-0052
    • Center Hospital of the National Center for Global Health and Medicine
• Mexico
  • Mexico City, Mexico, 6170
    • ProcliniQ Investigacion Clinica Toriello Guerra, Tlalpan
  • Mérida, Mexico, 97070
    • Unidad de Atencion Medica e Investigacion en Salud
• Puerto Rico
  • PR
    • San Juan, PR, Puerto Rico, 00935
      • Proyecto ACTU
    • San Juan, PR, Puerto Rico, 00909
      • HOPE Clinical Research
• South Korea
  • Daegu, South Korea, 41944
    • Kyungpook National University Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, *04564
    • National Medical Center
  • Seoul, South Korea, 137-701
    • The Catholic University of Korea, Seoul St. Mary's Hospital
• Spain
  • Badalona Barcelona, Spain, 8916
    • Hospital Universitario Germans Trias i Pujol
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz - PPDS
  • Seville, Spain, 4103
    • Hospital Universitario Virgen del Rocio - PPDS
  • Valencia, Spain, 46014
    • Consorcio Hospital General Universitario de Valencia
• Taiwan
  • Kaohsiung City, Taiwan, 81362
    • Kaohsiung Veterans General Hospital
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taoyuan City, Taiwan, 33004
    • Taoyuan General Hospital, Ministry of Health and Welfare
• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • Liverpool University Hospitals NHS Foundation Trust, Royal Liverpool Hospital
  • London, United Kingdom, WC1E 6JB
    • Mortimer Market Centre
  • London, United Kingdom, SE5 9RS
    • King's College Hospital, Weston Education Centre
  • London, United Kingdom, SW109NH
    • Chelsea and Westminster Hospital NHS Foundation Trust, St Stephen's Centre, Chelsea and Westminster Hospital
  • London, United Kingdom, W2 1NY
    • St Mary's Hospital - PPDS
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Pueblo Family Physicians
  • California
    • Berkeley, California, United States, 48072
      • Be Well Medical Center
    • Beverly Hills, California, United States, 90211
      • Pacific Oaks Medical Group
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group Inc.
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center, Summit Campus, East Bay Advanced Care
    • Palm Springs, California, United States, 92262
      • BIOS Clinical Research
    • San Diego, California, United States, 92103
      • UCSD Anti Viral Research Centre (AVRC)
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    • West Hollywood, California, United States, 90046
      • Mills Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80204
      • Public Health Institute at Denver Health
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine (study visits)
  • Florida
    • DeLand, Florida, United States, 32720
      • Midland Florida Infectious Diseases Specialists, PL - Orange City
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Center
    • Fort Lauderdale, Florida, United States, 33316
      • CAN Community Health
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami, Florida, United States, 33133
      • AIDS Healthcare Foundation - The Kinder Medical Group
    • Miami, Florida, United States, 33136
      • Schiff Center for liver Diseases/University of Miami
    • Miami Lakes, Florida, United States, 33016
      • Floridian Clinical Research
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • Bliss Healthcare
    • Pensacola, Florida, United States, 32503
      • AHF Pensacola
    • Sarasota, Florida, United States, 34237
      • CAN community Health
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A.
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Macon, Georgia, United States, 31201
      • Mercer University, Department of Internal Medicine
  • Massachusetts
    • Springfield, Massachusetts, United States, 01105
      • Claudia T Martorell MD LLC dba The Research Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • KC Care health Center
    • St Louis, Missouri, United States, 63139
      • Southampton Community Healthcare, Inc.
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • ID Care, LLC
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School - Clinical Research Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • AXCES Research Group, LLC
  • New York
    • Flushing, New York, United States, 11355
      • New York-Presbyterian Queens
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • The Brody School of Medicine at East Carolina University , ECU Adult Specialty Care
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Health and Wellness
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT Community Health Centers
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC) Research Nexus
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Bellaire, Texas, United States, 77401
      • St Hope Foundation, Inc.
    • Dallas, Texas, United States, 75208
      • AIDS Arms, Inc. DBA Prism Health North Texas
    • 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.
  • 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
    • Tacoma, Washington, United States, 98405
      • Community Health care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Currently receiving B/F/TAF for at least 6 months prior to screening.
• If plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) measurements in the last 6 months prior to screening are available, all levels must be < 50 copies/mL.
• At least one documented HIV-1 RNA level measured between 6 and 12 months (± 2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be < 50 copies/mL.
• Plasma HIV-1 RNA levels < 50 copies/mL at screening.
• No documented or suspected resistance to BIC (including integrase strand-transfer inhibitor resistant (INSTI-R) mutations T66A/I/K, E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene).
• No documented or suspected resistance to tenofovir alafenamide (TAF) (TAF; mutations K65R, K65N, K70E, Q151M or T69 insertion, or ≥ 3 of the following thymidine analog mutations [M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R] in the reverse transcriptase gene).
• Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance.

Key Exclusion Criteria:

• Positive serum pregnancy test or pregnant at screening or a positive pregnancy test prior to Day 1 randomization.

• Breastfeeding (nursing).

• Prior use of, or exposure to, LEN.

• Active, serious infections (other than HIV-1) requiring parenteral therapy < 30 days prior to randomization.

• Active tuberculosis infection.

• Acute hepatitis < 30 days before randomization.

• Chronic hepatitis B virus (HBV) infection, as determined by either:

  • Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit.
  • Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.

• Known hypersensitivity to the study drug, its metabolites, or any formulation excipient.

• History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).

• Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant as determined by the investigator.

• Active malignancy requiring acute systemic therapy.

• Any of the following laboratory values at screening:

  • Alanine aminotransferase > 5 × upper limit of normal (ULN).
  • Direct bilirubin > 1.5 × ULN.
  • Platelets < 50,000/mm^3.
  • Hemoglobin < 8.0 g/dL.

• Requirement for ongoing therapy with or prior use of any prohibited medications listed in the protocol.

• Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor.

• Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.

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: Treatment Group 1: BIC/LEN 75/50 mg; Participants will switch from bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed-dose combination (FDC) tablets to bictegravir/lenacapavir (BIC/LEN) 75/50 mg FDC tablets + placebo-to-match (PTM) B/F/TAF tablets, administered orally, once daily up to 48 weeks. Participants will also receive a 2-day oral pharmacokinetic (PK) loading dose of LEN 600 mg on Days 1 and 2, in addition to the daily doses of BIC/LEN 75/50 mg and PTM B/F/TAF tablets starting on Day 1. At the end of blinded treatment (EBT) participants will enter the open label (OL) phase and continue to receive BIC/LEN 75 mg/50 mg FDC tablets through at least 48 weeks in the OL phase. At the OL Week 48, participants will be given an option to continue to receive BIC/LEN FDC tablets.	Drug: Lenacapavir; Tablets administered orally without regard to food; Other Names: GS-6207; Drug: Bictegravir/Lenacapavir (BIC/LEN) FDC; Tablets administered orally without regard to food; Other Names: Bixlenvo™; Drug: Placebo to match B/F/TAF; Tablets administered orally without regard to food
Active Comparator: Blinded Phase: Treatment Group 2: B/F/TAF 50/200/25 mg; Participants will continue with their B/F/TAF 50/200/25 mg tablets and start PTM BIC/LEN tablets on Day 1 administered orally, once daily up to 48 weeks. Participants will receive PTM oral LEN PK loading tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2). Participants who complete the EBT will be given an option to enter the OL phase to receive BIC/LEN FDC tablets.	Drug: B/F/TAF; Tablets administered orally without regard to food; Other Names: Biktarvy ®; Drug: Placebo to match BIC/LEN FDC; Tablets administered orally without regard to food; Drug: Placebo to match Lenacapavir; Tablets administered orally without regard to food
Experimental: Open-label Phase: BIC/LEN 75/50mg; Participants from Treatment Group 1 will receive BIC/LEN FDC tablets through at least OL Week 48. At the OL Week 48 visit, participants from Treatment Group 1 will be given the option to continue to receive BIC/LEN FDC tablets. Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets. Participants from Treatment Group 2 who enter the OL phase will also receive a 2-day oral loading dose of LEN 600 mg (2 × 300 mg LEN on Day 1 and on Day 2). All participants who enter the OL phase may continue to receive BIC/LEN FDC tablets daily until study drug is available or until Gilead Sciences (Gilead) elects to discontinue the study.	Drug: Lenacapavir; Tablets administered orally without regard to food; Other Names: GS-6207; Drug: Bictegravir/Lenacapavir (BIC/LEN) FDC; Tablets administered orally without regard to food; Other Names: Bixlenvo™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) ≥ 50 Copies/mL at Week 48 as Determined by the United States Food and Drug Administration (US FDA) Defined Snapshot Algorithm	Participants who had the last available on-treatment HIV-1 RNA≥ 50 copies/mL in the Week 48 analysis window, or who did not have on-treatment HIV-1 RNA data in the Week 48 analysis window and participants who discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or who discontinued study drug prior to or in the Week 48 analysis window due to reasons other than adverse event (AE), death, or lack of efficacy and have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL were included. The Week 48 window was between Days 295 and 378 (inclusively). Percentages were rounded off.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-Defined Snapshot Algorithm	Participants who had the last available on-treatment HIV-1 RNA < 50 copies/mL in the Week 48 analysis window were included. The Week 48 window for snapshot algorithm was between Days 295 and 378 (inclusively). Percentages were rounded off.	Week 48
Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 48		Baseline, Week 48
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Through Week 48	An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily had a causal relationship with the treatment. TEAEs were defined as any AE that begins on or after the date of first dose of study drug up to the date of last dose of study drug plus 60 days (for BIC/LEN FDC, Treatment Group 1) or 30 days (for B/F/TAF, Treatment Group 2) or any AE leading to study drug discontinuation. Percentages were rounded off.	First dose date up to Week 48
Treatment Group 1: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-Defined Snapshot Algorithm		Week 96
Treatment Group 1: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by US FDA-Defined Snapshot Algorithm		Week 96
Treatment Group 1: Change From Baseline in CD4 Cell Count at Week 96		Week 96
Treatment Group 1: Percentage of Participants Experiencing Treatment-Emergent AEs Through Week 96		First dose date up to Week 96
Treatment Group 1: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 144 as Determined by the US FDA-Defined Snapshot Algorithm		Week 144
Treatment Group 1: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144 as Determined by US FDA-Defined Snapshot Algorithm		Week 144
Treatment Group 1: Change From Baseline in CD4 Cell Count at Week 144		Week 144
Treatment Group 1: Percentage of Participants Experiencing Treatment-Emergent AEs Through Week 144		First dose date up to Week 144

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Arora P, Hindman JT, West S, Ling J, Palaparthy R, Marathe DD. The effect of antacid and mineral supplements on bictegravir pharmacokinetics: results from a Phase 1, open-label, drug-drug interaction study. Antimicrob Agents Chemother. 2026 Jan 7;70(1):e0078125. doi: 10.1128/aac.00781-25. Epub 2025 Nov 28.
• Meissner EG, Ramgopal M, Ruane PJ, Sanchez W, Crofoot G, Routy JP, Brinson C, DeJesus E, Martorell CT, Tellez M, Yokomaku Y, O'Reilly M, Lupo S, Schellberg S, Lezama-Mora JI, Chin B, Aizen K, D'Antoni ML, Huang H, Mponponsuo K, Montezuma-Rusca JM, Sklar P, Rhee M, Hung CC; ARTISTRY-2 Study Group. Safety and efficacy of switching to bictegravir-lenacapavir versus continuing bictegravir-emtricitabine-tenofovir alafenamide in virologically suppressed people with HIV-1 (ARTISTRY-2): a double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet HIV. 2026 Aug;13(8):e538-e547. doi: 10.1016/S2352-3018(26)00078-0. Epub 2026 May 6.

Helpful Links

• <p>Gilead Clinical Trials Website</p>

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2024
• Primary Completion (Actual): October 27, 2025
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): November 5, 2026
• Last Update Submitted That Met QC Criteria: October 15, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: lenacapavir; bictegravir; bictegravir, emtricitabine, tenofovir alafenamide, drug combination
• Other Study ID Numbers: GS-US-621-6290; 2023-510022-33 (Other Identifier: European Medicines Agency); jRCT2051240046 (Registry Identifier: Japan Registry); 2023 (U.S. NIH Grant/Contract)

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