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

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified January 2026 by Gilead Sciences
Sponsor
Gilead Sciences
Information Provided by (Responsible Party)
Gilead Sciences
Clinicaltrials.gov Identifier
NCT06101342
Other Study ID Numbers:
GS-US-528-6363
First Submitted
October 19, 2023
First Posted
October 25, 2023
Last Update Posted
March 1, 2026
Last Verified
January 2026

ClinicalTrials.gov processed this data on February 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Pre-Exposure Prophylaxis of HIV Infection
Drug: Lenacapavir InjectionDrug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)Drug: Lenacapavir InjectionDrug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)

Study Design

Study TypeInterventional
Actual Enrollment181 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposePrevention
Official TitleA 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
Study Start DateDecember 12, 2023
Actual Primary Completion Date1yr 6mos from now
Actual Study Completion Date1yr 6mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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 Injection
Administered subcutaneously
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
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 Injection
Administered subcutaneously
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

Outcome Measures

Primary Outcome Measures
  1. Pharmacokinetic (PK) Parameter: Ctrough for Lenacapavir (LEN): LEN Plasma concentration at the End of the Dosing Interval (Week 26)
  2. PK Parameter: Ctrough for LEN: LEN Plasma concentration at the End of the Dosing Interval (Week 52)
  3. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
  4. Percentage of Participants Experiencing Treatment-emergent Clinical Laboratory Abnormalities with LEN and F/TDF
Secondary Outcome Measures
  1. General Acceptability of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Acceptability Questionnaire Responses
    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.
  2. Satisfaction With Use of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Satisfaction Questionnaire Responses
    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.
  3. Willingness to Use LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Willingness to Use Questionnaire Responses
    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.
  4. Number of Participants with Adherence to LEN, as Assessed by On-time LEN Injections Received
  5. 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)

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersYes
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.

Contacts and Locations

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