Study of Lenacapavir and Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) for Prevention of HIV in People Who Inject Drugs (HPTN 103) (PURPOSE 4)

February 27, 2026 updated by: Gilead Sciences

A Phase 2, Open-Label, Multicenter, Randomized Study to Evaluate the Pharmacokinetics and Safety of Twice Yearly Long-Acting Subcutaneous Lenacapavir for Pre-Exposure Prophylaxis in People Who Inject Drugs

The goals of this clinical study are to look at how lenacapavir (LEN) passes through the body and to assess the safety of LEN and emtricitabine/tenofovir disoproxil fumarate (F/TDF) for pre-exposure prophylaxis (PrEP) in people who inject drugs (PWID) in the United States (US).

The primary objectives of this study are to characterize the pharmacokinetics (PK) of LEN and to evaluate the safety of LEN and F/TDF for PrEP in US PWID.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

181

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90038
        • UCLA Vine Street Clinic
      • San Diego, California, United States, 92103
        • UCSD AntiViral Research Center (AVRC)
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami - Converge Miami Building
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Medicine Institute for Clinical and Translational Research, Clinical Research
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Rutgers New Jersey Medical School, Department of Medicine
    • New York
      • The Bronx, New York, United States, 10451
        • ICAP at Columbia University- Bronx Prevention Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania, Division of Infectious Diseases Penn Prevention Research Unit
    • Texas
      • Houston, Texas, United States, 77030
        • Houston AIDS Research Team CRS
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Key Inclusion Criteria:

  • Urine drug screen positive for any drug of misuse including, but not limited to, opioids (eg, fentanyl, heroin), stimulants (eg, cocaine, amphetamines), psychoactive drugs (eg, benzodiazepines), or a combination of these drugs.
  • Evidence of recent injection (eg, track marks).
  • Self-report of injection paraphernalia sharing in the prior 30 days.
  • Hepatitis B virus (HBV) surface antigen (HBsAg) negative.
  • Negative local rapid HIV-1/2 antibody (Ab)/antigen (Ag) test, central HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT).
  • Estimated glomerular filtration rate (GFR) at least 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr).

Key Exclusion Criteria:

  • Self-reported history of previous positive results on an HIV test.
  • Any reactive or positive HIV test result at screening or enrollment, even if HIV infection is not confirmed.
  • Coenrollment in any other interventional research study or other concurrent studies that may interfere with this study (as provided by self-report or other available documentation) without prior approval from the Medical Monitor/Joint Clinical Management Committee while participating in this study.
  • Past or current participation in HIV vaccine or HIV broadly neutralizing antibody study unless individual provides documentation of receipt of placebo (ie, not active product).
  • Prior use of long-acting systemic pre-exposure prophylaxis (PrEP) (including cabotegravir (CAB) or islatravir studies).
  • Acute viral hepatitis A or acute or chronic hepatitis B or C infection.
  • Have a suspected or known active, serious infection(s) (eg, active tuberculosis, etc).
  • Evidence of moderate or severe liver fibrosis or a history of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, variceal bleeding). In individuals with active hepatitis C, Fibrosis-4 (FIB-4) score > 3.25 (formula provided below).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Randomized Phase: Lenacapavir (LEN) Group
Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2.
Drug: Lenacapavir Tablet
Administered orally
Other Names:
  • GS-6207
Drug: Lenacapavir Injection
Administered subcutaneously
Other Names:
  • GS-6207
  • Yeztugo®
Experimental: Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group
Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks.
Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)
Administered orally
Other Names:
  • Truvada®
Experimental: Open-label Extension Phase: LEN
Participants randomized to LEN in the Randomized Phase who choose to participate in the LEN Open-Label Extension (OLE) Phase will receive SC LEN every 26 weeks (± 7 days) and have study visits every 13 weeks (± 7 days). Participants randomized to F/TDF in the Randomized Phase who choose to participate in LEN OLE Phase will switch to SC LEN and have study visits at LEN OLE Day 1, Week 4 (± 2 days), Week 13 (± 7 days), and every 13 weeks (± 7 days) thereafter. SC LEN will be administered at the LEN OLE Day 1 visit and every 26 weeks thereafter. These participants will also receive loading doses of oral LEN on OLE Days 1 and 2. Upon completion of the LEN OLE Phase, participants will transition to local HIV prevention services and return for a 30-day follow-up visit. At that time, participation in the study will end.
Drug: Lenacapavir Tablet
Administered orally
Other Names:
  • GS-6207
Drug: Lenacapavir Injection
Administered subcutaneously
Other Names:
  • GS-6207
  • Yeztugo®
Experimental: Pharmacokinetic (PK) Tail Phase: F/TDF
Participants eligible for the PK Tail Phase will receive open-label oral F/TDF once daily for up to 78 weeks and complete study visits every 13 weeks (± 7 days). PK Tail Day 1 visit will occur 26 weeks (± 7 days) after the last SC LEN injection.
Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)
Administered orally
Other Names:
  • Truvada®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic (PK) Parameter: Ctrough for Lenacapavir (LEN): LEN Plasma concentration at the End of the Dosing Interval (Week 26)
Time Frame: Week 26
Week 26
PK Parameter: Ctrough for LEN: LEN Plasma concentration at the End of the Dosing Interval (Week 52)
Time Frame: Week 52
Week 52
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Time Frame: First dose date up to 30 days post last dose at Week 78
First dose date up to 30 days post last dose at Week 78
Percentage of Participants Experiencing Treatment-emergent Clinical Laboratory Abnormalities with LEN and F/TDF
Time Frame: First dose date up to 30 days post last dose at Week 78
First dose date up to 30 days post last dose at Week 78

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
General Acceptability of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Acceptability Questionnaire Responses
Time Frame: Up to Week 52
To assess the acceptability of the study drug, the participants will complete questionnaire including a question on general acceptability of the assigned study drug on an ordinal 5-category scale with a response of: Completely unacceptable, Unacceptable, No opinion, Acceptable, or Completely acceptable.
Up to Week 52
Satisfaction With Use of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Satisfaction Questionnaire Responses
Time Frame: Up to Week 52
To assess the satisfaction with use of the study drug, the participants will complete questionnaire including a question on satisfaction with use of the assigned study drug on an ordinal 5-category scale with a response of: Very satisfied, Satisfied, Neutral, Dissatisfied, or Very dissatisfied.
Up to Week 52
Willingness to Use LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Willingness to Use Questionnaire Responses
Time Frame: Up to Week 52
To assess the willingness to use the study drug, the participants will complete questionnaire including a question on willingness to use the assigned study drug on an ordinal 5-category scale with a response of: Definitely Yes, Probably yes, Not sure/undecided, Probably No, or Definitely No.
Up to Week 52
Number of Participants with Adherence to LEN, as Assessed by On-time LEN Injections Received
Time Frame: Up to Week 26
Up to Week 26
Number of Participants with Adherence to F/TDF as Assessed by Adherence Levels Based on Intracellular Tenofovir-diphosphate (TFV-DP) Concentrations in Dried Blood Spot (DBS)
Time Frame: Up to Week 78
Up to Week 78

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Collaborators

National Institute on Drug Abuse (NIDA)
National Institute of Allergy and Infectious Diseases (NIAID)
HIV Prevention Trials Network

Investigators

  • Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 13, 2023

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

October 20, 2023

First Submitted That Met QC Criteria

October 20, 2023

First Posted (Actual)

October 26, 2023

Study Record Updates

Last Update Posted (Actual)

March 2, 2026

Last Update Submitted That Met QC Criteria

February 27, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-528-6363

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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