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

NCT07841990 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GS-US-782-8079-01
• Study Type: interventional
• Target: 125
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• 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

Study Arms (3)

Treatment Arm A: B/F/TAF

ACTIVE COMPARATOR

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

Treatment Arm B: GS-3242 + LEN

EXPERIMENTAL

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; Drug: Lenacapavir

Treatment Arm C: GS-3242 + LEN

EXPERIMENTAL

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; Drug: Lenacapavir

Interventions

B/F/TAF DRUG

Tablet administered orally

Also known as: Biktarvy®

Treatment Arm A: B/F/TAF

GS-3242 DRUG

Tablet administered orally

Treatment Arm B: GS-3242 + LEN; Treatment Arm C: GS-3242 + LEN

Lenacapavir DRUG

Tablet administered orally

Also known as: LEN

Treatment Arm B: GS-3242 + LEN; Treatment Arm C: GS-3242 + LEN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

MeSH Terms

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination; lenacapavir

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Central Study Contacts

Gilead Clinical Study Information Center

CONTACT

1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: September 25, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): July 1, 2033
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share