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

An Operationally Seamless Phase 2/3 Randomized, Open-label, Multicenter, Active-Controlled Study to Evaluate the Safety and Efficacy of Bictegravir/Lenacapavir Versus Stable Baseline Regimen in Virologically Suppressed People With HIV-1 on Stable Complex Treatment Regimens

The goal of this clinical study is to learn more about the effects of switching to the study drugs, bictegravir (BIC) plus lenacapavir (LEN), versus current therapy (Phase 2) and BIC/LEN fixed-dose combination (FDC) versus current therapy (Phase 3) in people living with HIV (PWH).

Study Overview

• Status: Active, not recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Bictegravir; Drug: Lenacapavir; Drug: Stable Baseline Regimen; Drug: BIC/LEN FDC

• Study Type: Interventional
• Enrollment (Actual): 689
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1202
    • Fundación Huésped
  • Buenos Aires, Argentina, 1072
    • Hospital General de Agudos J.M Ramon Mejia
  • Buenos Aires, Argentina, 1425
    • Helios Salud
• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St.Vincent's Hospital Sydney
    • Darlinghurst, New South Wales, Australia, 2011
      • Taylor Square Private Clinic
    • Sydney, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
• Canada
  • Decarie Montreal, Canada, H4A 3J1
    • Chronic Viral Illness Service / McGill University Health Centre (MUHC)
  • Montreal, Canada, H2L 0B1
    • Clinique Medicale du Quartier Latin
  • Ottawa, Canada, K1H 8L6
    • The Ottawa Hospital - General Campus
  • Regina, Canada, S4P 0W5
    • ID Clinic
  • Toronto, Canada, M5G 1K2
    • Maple Leaf Research
  • Vancouver, Canada, V6Z 2T1
    • Spectrum Health
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Instituto Dominicano de Estudio Virologicos - IDEV
• France
  • Nice, France, 6202
    • CHU Nice-Hopital L'Archet
  • Paris, France, 75010
    • Hospital Saint Louis
  • Paris, France, 75651
    • Hopital de la Pitie Salpetriere
  • Paris, France, 75018
    • Groupe Hospitalier Bichat Claude Bernard
• Germany
  • Berlin, Germany, 10439
    • zibp Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn
  • Frankfurt, Germany, 60596
    • Infektio Research GmbH & Co.KG
  • Hamburg, Germany, 20146
    • ICH Study Center GmbH & Co. KG
  • München, Germany
    • MVZ München am Goetheplatz
• Italy
  • Milan, Italy, 20157
    • Asst Fatebenefratelli Sacco
  • Milan, Italy, 20127
    • Irccs Ospedale San Raffaele
  • Modena, Italy, 40124
    • Azienda Ospedaliero-Universitaria di Modena
  • Roma, Italy, 00149
    • Istituto Nazionale Malattie Infettive "Lazzaro Spallanzani" IRCCS
  • Torino, Italy, 10149
    • ASL Città di Torino
• Japan
  • Nagoya, Japan
    • 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
• Puerto Rico
  • PR
    • San Juan, PR, Puerto Rico, 00909
      • HOPE Clinical Research
    • San Juan, PR, Puerto Rico, 00935
      • Proyecto ACTU
• South Africa
  • Cape Town, South Africa, 7925
    • Desmond Tutu Health Foundation Clinical Trials Unit
  • Ga-Rankuwa, South Africa, 208
    • Sefako Makgatho Health Sciences University
  • Johannesburg, South Africa, 2193
    • Ezintsha
• South Korea
  • Daegu, South Korea, 41944
    • Kyungpook National University Hospital
  • Daejeon, South Korea, 35015
    • Chungnam national university hospital
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Seoul, South Korea, 03722
    • Yonsei University Severance Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic Provincial De Barcelona
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal, Madrid
  • Seville, Spain, 4103
    • Hospital Universitario Virgen del Rocio
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung City, Taiwan, 81362
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • New Taipei City, Taiwan, 22060
    • Far Eastern Memorial Hospital
  • Taoyuan, Taiwan, 33004
    • TaoYuan General Hospital
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Department of HIV & Sexual Medicine
  • Brighton, United Kingdom, BN2 3EW
    • Brighton and Sussex University Hospitals NHS Trust
  • London, United Kingdom, E1 1BB.
    • Barts Health NHS Trust
  • London, United Kingdom, SE5 9RS
    • HIV medicine and infectious diseases
  • London, United Kingdom, SW109NH
    • St.Stephen's AIDS Trust, Clinical Trials Unit, 1st Floor, St.Stephen's Centre
• United States
  • 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
      • University of California San Diego (UCSD)
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor - UCLA Medical Center
    • West Hollywood, California, United States, 90046
      • The Men's Health Foundation
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University; School of Medicine; AIDS Program
  • Florida
    • DeLand, Florida, United States, 32720
      • Midland Florida Clinical Research Center, LLC
    • Fort Lauderdale, Florida, United States, 33316
      • Gary Richmond, MD, PA, Inc.
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Centers
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology & Research Center, LLC
    • 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, 32803
      • Therapeutic Concepts, PA
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute PA
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group
    • Macon, Georgia, United States, 31201
      • Mercer University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Kansas City Care Clinic
    • St Louis, Missouri, United States, 63139
      • Southampton Healthcare, Inc.
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Axces Research Group
  • New York
    • Flushing, New York, United States, 11355
      • New York Presbyterian Hospital
    • New York, New York, United States, 10001
      • Ricky K. Hsu, MD, PC
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina - Chapel Hill
    • Greenville, North Carolina, United States, 27858
      • East Carolina University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • 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
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants
    • Dallas, Texas, United States, 75208
      • AIDS Arms, Inc., DBA Prism Health North Texas
    • Fort Worth, Texas, United States, 76104
      • Texas Centers for Infectious Disease Associates
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot MD PA
    • Longview, Texas, United States, 75605
      • Diagnostic Clinic of Longview - Center for Clinical Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, MD

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• If plasma HIV-1 RNA measurements in the 6 months prior to screening are available, all levels must be < 50 copies/mL.
• At least one documented plasma 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.

• Currently receiving a complex antiretroviral (ARV) regimen due to previous viral resistance, or intolerance, or contraindication to existing single-tablet regimens (STR), and on this regimen for at least 6 months prior to the screening visit. The criteria to define a complex regimen in this study are as follows:

  • A regimen containing a boosted protease inhibitor or a nonnucleos(t)ide reverse transcriptase inhibitor (NRTI) plus at least 1 other third agent (ie, an agent from a class other than NRTIs) (eg, bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®)(BVY) + darunavir/cobicistat, BVY + etravirine), or
  • A regimen of ≥ 2 pills/day, or a regimen requiring dosing more than once daily, or
  • A regimen containing parenteral agent(s) (excluding a complete long-acting injectable regimen, such as intramuscular cabotegravir plus rilpivirine) as well as oral agents.
• No documented or suspected resistance to bictegravir (BIC).
• Estimated glomerular filtration rate ≥ 15 mL/min according to the Cockcroft-Gault formula for creatinine clearance (CLcr) who are not on renal replacement therapy.

Key Exclusion Criteria:

• Prior use of, or exposure to, lenacapavir (LEN)
• Active tuberculosis infection
• Chronic hepatitis B virus (HBV) infection

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: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2: Bictegravir (BIC) 75 mg + Lenacapavir (LEN) 25 mg; Participants will switch from their stable baseline regimen (SBR) to a regimen of BIC 75 mg + LEN 25 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 25 mg starting on Day 1 up to the end of randomized treatment (ERT) visit, participants will be treated for at least 24 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg fixed dose combination (FDC).	Drug: Bictegravir; Tablets administered orally without regard to food; Other Names: GS-9883; Drug: Lenacapavir; Tablets administered orally without regard to food; Other Names: GS-6207
Experimental: Phase 2: BIC 75 mg + LEN 50 mg; Participants will switch from their SBR to a regimen of BIC 75 mg + LEN 50 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 50 mg starting on Day 1 up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.	Drug: Bictegravir; Tablets administered orally without regard to food; Other Names: GS-9883; Drug: Lenacapavir; Tablets administered orally without regard to food; Other Names: GS-6207
Active Comparator: Phase 2: Stable Baseline Regimen (SBR); Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.	Drug: Stable Baseline Regimen; SBR will include a combination of antiretroviral (ARV) regimen. ARV regimen may include the following, except for participants taking a single tablet regimen or taking a complete parenteral regimen (Cabenuva).; Nucleos(t)ide Reverse Transcriptase Inhibitors:AbacavirEmtricitabineLamivudineTenofovir alafenamideTenofovir disoproxil fumarateZidovudine; Non-Nucleosite Reverse Transcriptase Inhibitors:DelavirdineEfavirenzNevirapineRilpivirineDoravirine; Integrase Inhibitors:BictegravirCabotegravirDolutegravirElvitegravirRaltegravir; Protease Inhibitors:AtazanavirDarunavirFosamprenavirIndinavirLopinavirNelfinavirSaquinavirTipranavir; Chemokine Co-receptor 5 (CCR5) Antagonist:Maraviroc; Fusion Inhibitors:Enfuvirtide; gp120 Attachment Inhibitor:Fostemsavir; Anti-CD4 Monoclonal Antibodies:Ibalizumab-uiyk
Experimental: Phase 3: BIC/LEN 75 mg/50 mg Fixed-dose Combination (FDC); Participants will switch from their SBR to a regimen of BIC/LEN 75 mg/50 mg FDC. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC/LEN 75 mg/50 mg FDC starting on Day 1 up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.	Drug: BIC/LEN FDC; Tablets administered orally without regard to food
Active Comparator: Phase 3: Stable Baseline Regimen; Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.	Drug: Stable Baseline Regimen; SBR will include a combination of antiretroviral (ARV) regimen. ARV regimen may include the following, except for participants taking a single tablet regimen or taking a complete parenteral regimen (Cabenuva).; Nucleos(t)ide Reverse Transcriptase Inhibitors:AbacavirEmtricitabineLamivudineTenofovir alafenamideTenofovir disoproxil fumarateZidovudine; Non-Nucleosite Reverse Transcriptase Inhibitors:DelavirdineEfavirenzNevirapineRilpivirineDoravirine; Integrase Inhibitors:BictegravirCabotegravirDolutegravirElvitegravirRaltegravir; Protease Inhibitors:AtazanavirDarunavirFosamprenavirIndinavirLopinavirNelfinavirSaquinavirTipranavir; Chemokine Co-receptor 5 (CCR5) Antagonist:Maraviroc; Fusion Inhibitors:Enfuvirtide; gp120 Attachment Inhibitor:Fostemsavir; Anti-CD4 Monoclonal Antibodies:Ibalizumab-uiyk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm	Week 24
Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm		Week 24
Phase 2: Change From Baseline in CD4 Cell Count at Week 24		Baseline, Week 24
Phase 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (AEs) Through Week 24		First dose date up to Week 24
Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Bictegravir (BIC) and Lenacapavir (LEN) at Steady State	Cmax is defined as the maximum observed concentration of drug.	Day 1 up to Week 24
Phase 2: PK Parameter: AUCtau of BIC and LEN at Steady State	AUCtau is defined as the area under the concentration versus time curve over the dosing interval.	Day 1 up to Week 24
Phase 2: PK Parameter: Ctau of BIC and LEN at Steady State	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Day 1 up to Week 24
Phase 3: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm		Week 48
Phase 3: Change From Baseline in CD4 Cell Count at Week 48		Baseline, Week 48
Phase 3: Percentage of Participants Experiencing Treatment-emergent AEs Through Week 48		First dose date up to Week 48
Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm		Week 96
Phase 3 (BIC/LEN 75 mg/50 mg FDC): Change From Baseline in CD4 Cell Count at Week 96		Baseline, Week 96
Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from Experiencing Treatment-emergent AEs Through Week 96		Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences
• 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): August 16, 2022
• Primary Completion (Actual): September 29, 2025
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: August 5, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 10, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: lenacapavir; bictegravir
• Other Study ID Numbers: GS-US-621-6289; 2022-500929-33 (Other Identifier: European Medicines Agency); DOH-27-052023-8574 (Other Identifier: South African Clinical Trial Registry); jRCT2051230168 (Other Identifier: Japan registry)

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