A Study of Teropavimab and Zinlirvimab in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection

A Phase 2 Randomized, Open-label Study to Evaluate the Safety and Efficacy of Broadly Neutralizing Antibodies (bNAbs) GS-5423 and GS-2872 in Combination With the Capsid Inhibitor Lenacapavir as Long-Acting Treatment Dosed Every 6 Months in Virologically Suppressed Adults With HIV-1 Infection

The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab (TAB; GS-5423) and zinlirvimab (ZAB; GS-2872)) with lenacapavir (LEN) in virologically suppressed adults with HIV-1 infection.

The purpose of this study is to evaluate the efficacy of switching to a regimen of LEN, TAB and ZAB, versus continuing on baseline oral antiretroviral therapy (ART) as determined by the proportion of participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 50 copies/mL at Week 26.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Lenacapavir Tablet; Drug: Lenacapavir Injection; Drug: Antiretroviral Therapy; Drug: Teropavimab; Drug: Zinlirvimab

Detailed Description

Participants will be randomized in Treatment Groups 1 and 2 to receive LEN, TAB, and ZAB, with differing doses of TAB and ZAB between the 2 groups and in Treatment Group 3 to continue their baseline oral ART for 52 weeks. Eligible participants in Treatment Groups 1 through 3 will have the option of participating in the study extension phase to receive LEN, TAB and ZAB after completing study follow-up through Week 52.

Treatment Group 2 was removed prior to dosing of all groups during Protocol Amendment 2.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • East Sydney Doctors
    • Sydney, New South Wales, Australia, 2010 NSW
      • Holdsworth House Medical Practice
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
• Canada
  • Toronto, Canada, M5G 1K2
    • Maple Leaf Research/Maple Leaf Medical Clinic
• Puerto Rico
  • San Juan, Puerto Rico, 909
    • Clinical Research Puerto Rico
• United States
  • California
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group, Inc.
    • San Diego, California, United States, 92103
      • UC San Diego (UCSD) AntiViral Research Center (AVRC)
    • San Francisco, California, United States, 94102
      • Optimus Medical Group
  • Colorado
    • Aurora, Colorado, United States, 80045
      • 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
    • DeLand, Florida, United States, 32720
      • Midland Florida Clinical Research Center, LLC
    • Fort Lauderdale, Florida, United States, 33316
      • Can Community Health Care
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A.
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown Infectious Disease Clinic
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
  • Missouri
    • St Louis, Missouri, United States, 63139
      • Southhampton Healthcare, Inc
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • AXCES Research Group, LLC
  • New York
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • NC TraCS Institute - CTRC; University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Health Center
    • Greensboro, North Carolina, United States, 27401
      • Regional Center for Infectious Disease Research
    • Greenville, North Carolina, United States, 27858
      • The Brody School of Medicine at East Carolina University
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Health and Wellness
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health - Clinical Research Unit
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St Jude Children's Research Hospital
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75208
      • AIDS Arms, Inc. DBA Prism Health North Texas
    • El Paso, Texas, United States, 79902
      • AXCES Research Group, LLC
    • Houston, Texas, United States, 77098
      • The Crofoot Research Center, INC
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Clinical Alliance for Research & Education, Infectious Diseases LLC (CARE-ID)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed.
• No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q).
• Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) < 50 copies/mL at screening visit 2.
• Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable.
• Proviral phenotypic sensitivity to both teropavimab and zinlirvimab by the PhenoSense Assay (Monogram Biosciences).
• Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2.

Key Exclusion Criteria:

• Comorbid condition requiring ongoing immunosuppression.
• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable.
• Evidence of current hepatitis B virus (HBV) infection regardless of HBV surface antigen status, at the screening visit 2.
• History of opportunistic infection or illness indicative of Stage 3 HIV disease.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Randomized Phase Treatment Group 1: LEN + TAB + ZAB; Participants will receive loading dose of lenacapavir (LEN) 600 mg tablets, orally, on Day 1 and Day 2. They will receive LEN 927 mg subcutaneous (SC) injection along with teropavimab (TAB) 2550 mg intravenous (IV) infusion and zinlirvimab (ZAB) 2550 mg IV infusion on Day 1 and every 26 weeks up to Week 52 in the Randomized Phase. At Week 52, participants in this group with HIV-1 RNA < 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will continue to receive their randomized study drugs every 26 weeks.	Drug: Lenacapavir Tablet; Administered orally; Other Names: GS-6207; Drug: Lenacapavir Injection; Administered subcutaneously; Other Names: GS-6207; Sunlenca®; Drug: Teropavimab; Administered intravenously; Other Names: GS-5423, 3BNC117-LS; Drug: Zinlirvimab; Administered intravenously; Other Names: GS-2872, 10-1074-LS
Experimental: Randomized Phase Treatment Group 3: SBR; Participants in Stay on Baseline Regimen (SBR) group will continue their baseline oral antiretroviral therapy (ART) up to Week 52. Antiretroviral therapy will include drugs like bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide, administered as per standard of care. At Week 52, participants in this group with HIV-1 RNA < 50 copies/mL and in the absence of confirmed virologic rebound throughout the Randomized Phase of the study will switch from oral ART to LEN, TAB and ZAB, every 26 weeks. The participants will switch to receive LEN, TAB, and ZAB every 26 weeks beginning at Week 52.	Drug: Antiretroviral Therapy; Antiretroviral therapy, administered orally may include regimens such as: bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide.
Experimental: Extension Phase: Treatment Group 1: LEN + TAB + ZAB; At Week 52, participants in this group with HIV-1 RNA < 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will receive LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion.	Drug: Lenacapavir Injection; Administered subcutaneously; Other Names: GS-6207; Sunlenca®; Drug: Teropavimab; Administered intravenously; Other Names: GS-5423, 3BNC117-LS; Drug: Zinlirvimab; Administered intravenously; Other Names: GS-2872, 10-1074-LS
Experimental: Extension Phase Treatment Group 3: SBR; At Week 52, participants in this group will be given the option to participate in the Extension Phase to switch from oral ART to LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion, every 26 weeks at the dose specified for Treatment Group 1.	Drug: Lenacapavir Tablet; Administered orally; Other Names: GS-6207; Drug: Lenacapavir Injection; Administered subcutaneously; Other Names: GS-6207; Sunlenca®; Drug: Teropavimab; Administered intravenously; Other Names: GS-5423, 3BNC117-LS; Drug: Zinlirvimab; Administered intravenously; Other Names: GS-2872, 10-1074-LS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 Copies/mL at Week 26 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm	Percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using US FDA-defined snapshot algorithm, which defines a participant's virologic outcome and included participants a) who had last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 26 analysis window; or b) who did not have on-treatment HIV-1 RNA data in the Week 26 analysis window and i) discontinued study drug prior to or in the Week 26 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 26 analysis window due to adverse event (AE) or death and had last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 26 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL. Clopper-Pearson exact method was used to calculate the 95% confidence interval (CI) for the outcome measure of each treatment. Percentages were rounded off.	Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm	Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 26 was analyzed using the US FDA-defined snapshot algorithm, which defined a participant's virologic outcome and included participants who had the last available on-treatment HIV-1 RNA < 50 copies/mL in the Week 26 analysis window. The Clopper-Pearson exact method was used to calculate the 95% CI for the outcome measure of each treatment. Percentages were rounded off.	Week 26
Change From Baseline in Clusters of Differentiation 4 (CD4) + T-cell Counts at Week 26		Baseline, Week 26
Change From Baseline in CD4+ T-cell Counts at Week 52		Baseline, Week 52
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)		Up to approximately 6 years
Pharmacokinetic (PK) Parameter: AUC0-tau for TAB and ZAB	AUC0-tau is defined as the partial area under the concentration versus time curve from time "0" to time "t".	Up to approximately 6 years
PK Parameter: t1/2 for TAB and ZAB	t1/2 is defined as the terminal elimination half-life.	Up to approximately 6 years
PK Parameter: Cmax for TAB and ZAB	Cmax is defined as the maximum observed concentration of drug.	Up to approximately 6 years
PK Parameter: Cmax for LEN	Cmax is defined as the maximum observed concentration of drug.	Up to approximately 6 years
PK Parameter: Tmax for TAB, ZAB, and LEN	Tmax is defined as the time (observed time point) of Cmax.	Up to approximately 6 years
Percentage of Participants With Treatment-emergent Anti-TAB and Anti-ZAB Antibodies	Anti-TAB and anti-ZAB antibodies incidence referred to the percentage of participants who have treatment-emergent anti-TAB and anti-ZAB antibodies among all participants evaluable for anti-drug antibody (ADA) incidence.	Up to approximately 6 years
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm	Percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 52 was analyzed using US FDA-defined snapshot algorithm, which defines a participant's virologic outcome and included participants a) who had last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 52 analysis window; or b) who did not have on-treatment HIV-1 RNA data in the Week 52 analysis window and i) discontinued study drug prior to or in the Week 52 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 52 analysis window due to adverse event (AE) or death and had last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 52 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL. Clopper-Pearson exact method was used to calculate the 95% confidence interval (CI) for the outcome measure of each treatment. Percentages were rounded off.	Week 52
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm	Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 52 was analyzed using the US FDA-defined snapshot algorithm, which defined a participant's virologic outcome and included participants who had the last available on-treatment HIV-1 RNA < 50 copies/mL in the Week 52 analysis window. The Clopper-Pearson exact method was used to calculate the 95% CI for the outcome measure of each treatment. Percentages were rounded off.	Week 52
Trough Concentration at Week 26 Predose for TAB and ZAB	Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.	Week 26 predose
Trough Concentration at Week 26 Predose for LEN	Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.	Week 26 predose
Trough Concentration at Week 52 Predose for TAB and ZAB	Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.	Week 52 predose
Trough Concentration at Week 52 Predose for LEN	Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.	Week 52 predose

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Mponponsuo K, McMahon JH, Gorgos L, Morales-Ramirez J, Workowski K, Brunetta J, Ogbuagu O, Collins SE, VanderVeen LA, Huang H, Baeten JM, Eron JJ. Efficacy and Safety of Lenacapavir, Teropavimab, and Zinlirvimab: Phase II Week 26 Primary Outcome [Oral 07]. Conference on Retroviruses and Opportunistic Infections (CROI); 2025 9-12 March, San Francisco, CA.
• Ogbuagu O, Gaur A, McMahon JH, Gorgos L, Morales-Ramirez JO, Workowski K, Brunetta J, Mponponsuo K, Collins SE, VanderVeen LA, Zhang N, Huang H, Baeten JM, Eron J. Efficacy and safety of lenacapavir, teropavimab, and zinlirvimab: week-26 primary outcome results from a multicentre, open-label, randomised, active-controlled, phase 2 study. Lancet Microbe. 2026 Mar;7(3):101283. doi: 10.1016/j.lanmic.2025.101283. Epub 2026 Feb 17.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): July 2, 2024
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (Actual): February 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Therapeutics; Drug Therapy; Drug Therapy, Combination; lenacapavir; Antiretroviral Therapy, Highly Active
• Other Study ID Numbers: GS-US-536-5939

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