Substudy-01: A Study of Long-Acting HIV-1 Treatments Taken by Mouth in People With HIV-1 With Undetectable Virus Levels

A Platform, Active-Controlled Study Evaluating the Safety and Efficacy of Long-Acting Oral Regimens in People With HIV-1; Substudy-01: Phase 2, Open-Label, Weekly, Long-Acting, Oral Regimens in Virologically Suppressed People With HIV-1

Master Protocol: The main goal of this master clinical study is to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) of long-acting oral (LAO) regimens in people with HIV-1 (PWH).

The main goal of this Substudy-01 is to assess the safety, tolerability, effectiveness, and PK of switching to weekly LAO regimens, including GS-3242 + LEN, versus continuing on once daily oral bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®) in PWH with controlled HIV infection, B/F/TAF for at least 6 months prior to study start.

The primary objective is to evaluate the efficacy of switching to each LAO regimen versus continuing B/F/TAF in virologically suppressed PWH at Week 24.

Study Overview

• Status: Recruiting
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: B/F/TAF; Drug: GS-3242; Drug: Lenacapavir

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gilead Clinical Study Information Center; Phone Number: 1-833-445-3230 (GILEAD-0); Email: GileadClinicalTrials@gilead.com

Study Locations

• United States
  • Florida
    • Ft. Pierce, Florida, United States, 34982
      • Recruiting
      • Midway Immunology and Research Center
  • Texas
    • Houston, Texas, United States, 77098
      • Recruiting
      • The Crofoot Research Center, INC

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:

• Individuals assigned male or female at birth, 18 years of age or older, able to understand and give written informed consent and comply with treatment and follow-up.
• Individuals assigned male or female at birth who are of childbearing potential and engage in heterosexual intercourse must agree to use approved method(s) of contraception.
• Negative serum pregnancy test at screening and negative urine test at enrollment.
• Receiving B/F/TAF for ≥ 6 months prior to screening.
• Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months before and at screening.
• No resistance to GS-3242 (integrase mutation Q148H/K/R plus at least 2 of the following integrase mutations: L74I/M, T97A, E138A/K/T, or G140A/C/S) on available historical resistance reports.
• CD4 ≥ 200 cells/mm^3 at screening

Key Exclusion Criteria:

• Plans to breastfeed during the study period and 60 days following the last dose of study intervention.
• History of virologic failure while on an integrase strand-transfer inhibitor-based regimen.
• Creatinine clearance according to the Cockcroft-Gault formula < 60 mL/min.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment Arm A: B/F/TAF; Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks. After Week 48, participants in the Randomized Phase may be offered to continue to receive study drug in the Extension Phase.	Drug: B/F/TAF; Tablet administered orally; Other Names: Biktarvy®
Experimental: Treatment Arm B: GS-3242 + LEN; Participants will be randomized to oral loading dose of GS-3242 in combination with LEN, followed by a once-weekly oral combination regimen of GS-3242 and LEN (at a different dose than Treatment C), administered concomitantly for at least 48 weeks. After Week 48, participants in the Randomized Phase may be offered to continue to receive study drug in the Extension Phase.	Drug: GS-3242; Tablet administered orally; Drug: Lenacapavir; Tablet administered orally; Other Names: LEN
Experimental: Treatment Arm C: GS-3242 + LEN; Participants will be randomized to oral loading dose of GS-3242 in combination with LEN, followed by a once-weekly oral combination regimen of GS-3242 and LEN (at a different dose than Treatment Arm B), administered concomitantly for at least 48 weeks. After Week 48, participants in the Randomized Phase may be offered to continue to receive study drug in the Extension Phase.	Drug: GS-3242; Tablet administered orally; Drug: Lenacapavir; Tablet administered orally; Other Names: LEN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants With HIV-1 Ribonucleic Acid (RNA) ≥ 50 copies/mL at Week 24 as Determined by the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Weeks 12 as Determined by the US FDA-defined Snapshot Algorithm		Week 12
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 Week 12 as Determined by the US FDA-defined Snapshot Algorithm		Week 12
Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm		Week 24
Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm		Week 48
Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 12		Week 12
Change From Baseline in CD4 Cell Count at Week 24		Week 24
Change From Baseline in CD4 Cell Count at Week 48		Week 48
The Percentage of Participants Experiencing Treatment-Emergent Aadverse Events (TEAEs) Through Week 12		Week 12
The Percentage of Participants Experiencing Treatment-Emergent Aadverse Events (TEAEs) Through Week 24		Week 24
The Percentage of Participants Experiencing Treatment-Emergent Aadverse Events (TEAEs) Through Week 48		Week 48
Pharmacokinetic (PK) Parameter: Cmax of GS-3242	Cmax is defined as the maximum observed concentration of drug.	Up to 48 weeks
PK Parameter: Tmax of GS-3242	Tmax is defined as the time (observed time point) of Cmax.	Up to 48 weeks
PK Parameter: Ctau of GS-3242	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Up to 48 weeks
PK Parameter: AUCtau of GS-3242	AUCtau is defined as the area under the concentration versus time curve over the dosing interval.	Up to 48 weeks

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• <p>Related Info</p>

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): July 1, 2033

Study Registration Dates

• First Submitted: September 21, 2026
• First Submitted That Met QC Criteria: September 21, 2026
• First Posted (Actual): September 25, 2026

Study Record Updates

• Last Update Posted (Actual): October 23, 2026
• Last Update Submitted That Met QC Criteria: October 21, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: lenacapavir; bictegravir, emtricitabine, tenofovir alafenamide, drug combination
• Other Study ID Numbers: GS-US-782-8079-01

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