Pre-Exposure Prophylaxis of HIV InfectionPhase 2PURPOSE 4NCT06101342

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

A Phase 2 study testing Lenacapavir Injection, Lenacapavir Tablet and Emtricitabine/tenofovir disoproxil fumarate (F/TDF) in people with Pre-Exposure Prophylaxis of HIV Infection, run by Gilead Sciences at 9 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial summary

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). Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Pre-Exposure Prophylaxis of HIV Infection
What is being tested?: Lenacapavir Injection, Lenacapavir Tablet and Emtricitabine/tenofovir disoproxil fumarate (F/TDF)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 181 participants
Where: 9 sitesUnited States
Study dates: 13 Dec 2023to Jan 2028
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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).

Who cannot join

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.

Show all 9Show fewer

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.

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

United States9 sites

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

Other trials in United States

About this study

Official title: 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 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.

Conditions: Pre-Exposure Prophylaxis of HIV Infection
Being tested: Lenacapavir Injection, Lenacapavir Tablet, Emtricitabine/tenofovir disoproxil fumarate (F/TDF)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Lenacapavir InjectionDrug
Also called GS-6207, Yeztugo®
Administered subcutaneously
Lenacapavir TabletDrug
Also called GS-6207
Administered orally
Emtricitabine/tenofovir disoproxil fumarate (F/TDF)Drug
Also called Truvada®
Administered orally

Study groups in NCT06101342
Study group	Role	What they receive
Randomized Phase: Lenacapavir (LEN) Group	Experimental	Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2. Receives: Drug: Lenacapavir Injection; Drug: Lenacapavir Tablet
Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group	Experimental	Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks. Receives: Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)
Open-label Extension Phase: LEN	Experimental	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. Receives: Drug: Lenacapavir Injection; Drug: Lenacapavir Tablet
Pharmacokinetic (PK) Tail Phase: F/TDF	Experimental	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. Receives: Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (5)

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.
Measured: Up to Week 52
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.
Measured: 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
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.
Measured: Up to Week 52
Number of Participants with Adherence to LEN, as Assessed by On-time LEN Injections Received
Measured: 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)
Measured: Up to Week 78

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Dec 2023Jan 2028

First posted26 Oct 2023
Study start13 Dec 2023
Primary completion27 Jul 2026
Study completionJan 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pre-Exposure Prophylaxis of HIV InfectionStudies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 181 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06101342
Sponsor's protocol ID: GS-US-528-6363
Acronym: PURPOSE 4
Status last verified: Aug 2026
First submitted: 20 Oct 2023
Last updated: 13 Aug 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Martinez S, Garcia-Romeu A, Wisdom J, Jones J. Methamphetamine use and HIV prevention: a qualitative study on challenges and opportunities for PrEP utilization. AIDS Care. 2026 Apr;38(4):856-869. doi: 10.1080/09540121.2025.2611079. Epub 2026 Jan 7.
PubMed 41498432

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 3
Long-term Follow-up of Long-acting Cabotegravir (CAB LA) for PrEP (Pre-exposure Prophylaxis) in Participants at Risk of Acquiring HIV (Human Immunodeficiency Virus)
HIV Infections
Active, not recruiting
Evaluating the Effectiveness of a Mobile HIV Prevention App to Increase HIV and Sexually Transmitted Infections (STI) Testing and PrEP Initiation Among Rural Men Who Have Sex With Men
HIV Infections, STI
Not yet recruitingPhase 4
Starting HIV Prevention Medicine (PrEP) During an Emergency Department Visit With a Peer Navigator
HIV Prevention, Pre-Exposure Prophylaxis (PrEP)
Not yet recruiting
Evaluating the Healthy Families PrEP Program for Women at Risk for HIV
HIV, Pregnancy
RecruitingObservational study
Implementation Study of Lenacapavir Pre-exposure Prophylaxis for HIV Prevention
HIV Infections

All Pre-Exposure Prophylaxis of HIV Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT06101342
Acronym / sponsor ID: PURPOSE 4 / GS-US-528-6363
Conditions: Pre-Exposure Prophylaxis of HIV Infection
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 181 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Collaborators: HIV Prevention Trials Network, National Institute on Drug Abuse (NIDA), National Institute of Allergy and Infectious Diseases (NIAID)
Study start: 13 Dec 2023 (actual)
Primary completion: 27 Jul 2026 (actual)
Study completion: Jan 2028 (estimated)
First posted: 26 Oct 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Randomized Phase: Lenacapavir (LEN) Group	Experimental	Drug: Lenacapavir Injection, Drug: Lenacapavir TabletParticipants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2.
Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group	Experimental	Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks.
Open-label Extension Phase: LEN	Experimental	Drug: Lenacapavir Injection, Drug: Lenacapavir TabletParticipants 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.
Pharmacokinetic (PK) Tail Phase: F/TDF	Experimental	Drug: Emtricitabine/tenofovir disoproxil fumarate (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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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).

Key exclusion criteria (9 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Lenacapavir InjectionAlso: GS-6207, Yeztugo®Administered subcutaneously	Drug	Open-label Extension Phase: LEN, Randomized Phase: Lenacapavir (LEN) Group
Lenacapavir TabletAlso: GS-6207Administered orally	Drug	Open-label Extension Phase: LEN, Randomized Phase: Lenacapavir (LEN) Group
Emtricitabine/tenofovir disoproxil fumarate (F/TDF)Also: Truvada®Administered orally	Drug	Pharmacokinetic (PK) Tail Phase: F/TDF, Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group

Primary outcome

Pharmacokinetic (PK) Parameter: Ctrough for Lenacapavir (LEN): LEN Plasma concentration at the End of the Dosing Interval (Week 26)
Time frame: Week 26
PK Parameter: Ctrough for LEN: LEN Plasma concentration at the End of the Dosing Interval (Week 52)
Time frame: 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 52
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 52

5 secondary outcomes

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
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
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
Number of Participants with Adherence to LEN, as Assessed by On-time LEN Injections Received
Time frame: 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

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
Derived from this study: PubMed 41498432Martinez S, Garcia-Romeu A, Wisdom J, Jones J. Methamphetamine use and HIV prevention: a qualitative study on challenges and opportunities for PrEP utilization. AIDS Care. 2026 Apr;38(4):856-869. doi: 10.1080/09540121.2025.2611079. Epub 2026 Jan 7.
Gilead Clinical Trials WebsiteLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Pre-Exposure Prophylaxis of HIV Infection

Active, not recruitingPhase 3
Long-term Follow-up of Long-acting Cabotegravir (CAB LA) for PrEP (Pre-exposure Prophylaxis) in Participants at Risk of Acquiring HIV (Human Immunodeficiency Virus)
HIV Infections
Active, not recruiting
Evaluating the Effectiveness of a Mobile HIV Prevention App to Increase HIV and Sexually Transmitted Infections (STI) Testing and PrEP Initiation Among Rural Men Who Have Sex With Men
HIV Infections, STI
Not yet recruitingPhase 4
Starting HIV Prevention Medicine (PrEP) During an Emergency Department Visit With a Peer Navigator
HIV Prevention, Pre-Exposure Prophylaxis (PrEP)
Not yet recruiting
Evaluating the Healthy Families PrEP Program for Women at Risk for HIV
HIV, Pregnancy
RecruitingObservational study
Implementation Study of Lenacapavir Pre-exposure Prophylaxis for HIV Prevention
HIV Infections

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic (PK) Parameter: Ctrough for Lenacapavir (LEN): LEN Plasma concentration at the End of the Dosing Interval (Week 26) (time frame: Week 26). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06101342, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.