Pre-Exposure Prophylaxis of HIV InfectionPhase 3PURPOSE 1NCT04994509

Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection

A Phase 3 study testing Oral Lenacapavir (LEN), Subcutaneous (SC) Lenacapavir (LEN) and F/TAF in people with Pre-Exposure Prophylaxis of HIV Infection, run by Gilead Sciences at 28 sites in 2 countries.

Active, not recruiting

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

Official record

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Trial summary

The goal of this study is to evaluate the efficacy of the study drugs, lenacapavir (LEN) and emtricitabine/tenofovir alafenamide (F/TAF) in preventing HIV infection, in adolescent girls and young women (AGYW). Read more about this study

Who is it for?: Ages 16 to 25 years, women onlyHealthy volunteers can take part
Conditions the study is for: Pre-Exposure Prophylaxis of HIV Infection
What is being tested?: Oral Lenacapavir (LEN), Subcutaneous (SC) Lenacapavir (LEN) and F/TAF
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 5,368 participants
Where: 28 sitesin 2 countries
Study dates: 30 Aug 2021to Jan 2028
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 16 to 25 years
Women only
Healthy volunteers accepted
Child, Adult

Who may be able to join

Incidence Phase
HIV-1 status unknown at initial screening and no prior human immunodeficiency virus (HIV)-1 testing within the last 3 months.
Sexually active (has had > 1 vaginal intercourse within the last 3 months) with cisgender male individuals (CGM).
Randomized Phase
Negative fourth generation HIV-1 antibody (Ab)/antigen (Ag) test confirmed with central HIV-1 testing.
Estimated glomerular filtration rate (GFR) ≥ 60 mL/min at screening.
Body weight ≥ 35 kg.

Who cannot join

Prior receipt of an HIV vaccine.
Prior use of any long-acting systemic HIV pre-exposure prophylaxis (PrEP) or prior HIV postexposure prophylaxis (PEP) in the past 12 weeks.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

28 sites in 2 countries.

Country

City, postcode or hospital

28 sites in 2 countries

South Africa25 sites

Madibeng Centre for Research
Brits, 2500
Emavundleni Research Centre
Cape Town, 7750
Vuka Research Clinic
Cape Town, 7784
Desmond Tutu Health Foundation Clinical Trials Unit
Cape Town, 7925
Botha's Hill Clinical Research Site, HIV Prevention Research Unit
Durban, 3660
CAPRISA eThekwini Clinical Research Site
Durban, 4001
CAPRISA Vulindlela Clinical Research Site
Durban, 4001
MatCH Research Unit, Suite 1112, 11th Floor
Durban, 4001
Synergy Biomed Research Institute (SBRI)
East London
Setshaba Research Centre
Gauteng, 152
Wits Reproductive Health & HIV Institute (Wits RHI)
Johannesburg, 2038
The Aurum Institute: Gavin J Churchyard Legacy Centre, Klerksdorp Clinical Research Centre
Klerksdorp, 2571
Perinatal HIV Research Unit (PHRU) Soweto Kliptown
Kliptown, 1809
Phoenix Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit
Kwa Zulu Natal, 4061
Verulam Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit
Kwa Zulu Natal, 4340
Tongaat Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit
Kwa Zulu Natal, 4400
Chatsworth Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit
Kwa Zulu Natal
Qhakaza Mbokodo Research Clinic
Ladysmith, 3370
Africa Health Research Institute
Mtubatuba, 3935
The Aurum Institute: Pretoria Clinical Research Centre
Pretoria, 0087
The Aurum Institute: Rustenburg Clinical Research Centre
Rustenburg, 299
Desmond Tutu Health Foundation - Masiphumelele Research Office
Sunnydale, 7705
The Aurum Institute: Tembisa Clinical Research Centre
Tembisa, 1632
CAPRISA Umlazi Clinical Research Site
Umlazi, 4066
FPD-DTHF Ndevana Community Research Site
Vincent, 5217

Other trials in South Africa

Uganda3 sites

Makerere-Kalangala Clinical Research site
Kalangala
AMBSO Masaka Clinical Research site
Kyotera- Masaka Region
Makerere University- John Hopkins University (MU-JHU) Mityana Research Site (MU-JHU) Care Ltd
Mityana Town

Other trials in Uganda

About this study

Official title: A Phase 3, Double-Blinded, Multicenter, Randomized Study to Evaluate Safety and Efficacy of Twice Yearly Long-Acting Subcutaneous Lenacapavir, and Daily Oral Emtricitabine/Tenofovir Alafenamide for Pre-Exposure Prophylaxis in Adolescent Girls and Young Women at Risk of HIV Infection

The primary objective of this study is to evaluate the efficacy of LEN and F/TAF for HIV-1 PrEP in AGYW at risk of HIV-1 infection.

Conditions: Pre-Exposure Prophylaxis of HIV Infection
Being tested: Oral Lenacapavir (LEN), Subcutaneous (SC) Lenacapavir (LEN), F/TAF, F/TDF, Placebo SC LEN

What participants receive

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

Oral Lenacapavir (LEN)Drug
Also called GS-6207
Tablets administered orally without regard to food
Subcutaneous (SC) Lenacapavir (LEN)Drug
Also called GS-6207, Yeztugo®, Yeytuo®
Administered via SC injections
F/TAFDrug
Also called Descovy®
Tablets administered orally
F/TDFDrug
Also called Truvada®
Tablets administered orally
Placebo SC LENDrug
Administered via SC injections
PTM Oral LENDrug
Tablets administered orally
PTM F/TAFDrug
Tablets administered orally
PTM F/TDFDrug
Tablets administered orally

Study groups in NCT04994509
Study group	Role	What they receive
Randomized Blinded Phase: Lenacapavir	Experimental	Participants will receive lenacapavir (LEN) 927 mg injection, every 26 weeks starting on Day 1 for up to approximately 52 weeks. Participants will also receive loading dose of LEN 600 mg, tablet, once daily on Day 1 and Day 2. Participants will receive placebo to match (PTM) emtricitabine/tenofovir disoproxil fumarate (F/TDF) or PTM emtricitabine/tenofovir alafenamide (F/TAF), once daily, up to approximately 52 weeks. Receives: Drug: Oral Lenacapavir (LEN); Drug: Subcutaneous (SC) Lenacapavir (LEN); Drug: PTM F/TAF; Drug: PTM F/TDF
Randomized Blinded Phase: F/TAF	Experimental	Participants will receive F/TAF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks, starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2. Receives: Drug: F/TAF; Drug: Placebo SC LEN; Drug: PTM Oral LEN
Randomized Blinded Phase: F/TDF	Experimental	Participants will receive F/TDF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2. Receives: Drug: F/TDF; Drug: Placebo SC LEN; Drug: PTM Oral LEN
LEN Open-Label Extension (OLE) Phase	Experimental	After completion of the Blinded phase, participants will be offered entry into the LEN OLE Phase. Participants randomized to LEN will continue to receive LEN 927 mg injection, every 26 weeks until LEN becomes available or the sponsor elects to discontinue the study, whichever occurs first. Participants randomized to F/TAF or F/TDF will receive LEN 927 mg injection on OLE Day 1, Week 26, and every 26 weeks thereafter. Participants will also receive LEN 600 mg tablet on OLE Days 1 and 2. Receives: Drug: Oral Lenacapavir (LEN); Drug: Subcutaneous (SC) Lenacapavir (LEN)
Pharmacokinetic (PK) Tail Coverage Phase	Experimental	Participants who prematurely discontinue study drug in the randomized blinded phase will transition into the PK Tail Coverage phase. Participants will receive F/TDF, once daily, for 78 weeks beginning 26 weeks after the last LEN injection. Receives: Drug: F/TDF

What is being measured

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

Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY)
bHIV per 100 PY in the Incidence Phase was calculated using RITA.
The RITA incorporated HIV-1 testing results and recency assay testing results to estimate the bHIV. Recency assay testing was performed for participants in the All Screened Set found to have HIV-1 infection at the Incidence Phase Screening Visit as defined below. Participants were considered to have recent HIV-1 infection if the normalized optical density (ODn) was below 1.5 threshold using the Sedia limiting antigen avidity enzyme immunoassay (LAg-EIA) and the HIV-1 RNA (viral load) was > 75 copies/mL of blood.
HIV-1 infection was defined as participants having at least one of the following central lab results at the Incidence Phase screening visit:
- Positive HIV-1/2 differentiation Ab, OR
- Positive HIV-1 ribonucleic acid (RNA) qualitative test, OR
- HIV-1 RNA quantitative test ≥200 copies/mL.
Measured: Incidence Phase Screening Visit (Day 1)
Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN and F/TAF Compared to Participants in All Screened Set
HIV-1 incidence per 100 PY for LEN and F/TAF was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses.
HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples.
bHIV incidence per 100 PY in All Screened Set was estimated as described in outcome measure#1.
Measured: When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)

Secondary outcomes (5)

Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN, F/TAF and F/TDF
HIV-1 incidence per 100 PY was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses.
HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples.
Measured: When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)
Randomized Blinded Phase: HIV-1 Incidence Among Participants Adherent to LEN
A participant was defined as adherent to LEN if they have received all per-protocol administrations of LEN within 28 weeks since the previous administration. The incidence of HIV-1 infection per 100 PY calculation is defined in outcome measure #2.
Measured: When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)
Randomized Blinded Phase: Percentage of Participants Adherent to F/TAF in HIV-1 Diagnosed Participants and Their Matched Controls
A participant's adherence to F/TAF was measured by tenofovir diphosphate (TFV-DP) in dried blood spot (DBS) samples, where <450 fmol/punch associates with an adherence of <2 days per week. The data is reported in two categories: low adherence (<2 days per week) and not low adherence (>= 2 days per week).
Measured: When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)
Randomized Blinded Phase: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
TEAEs were defined as 1 or both of the following:
- Any adverse events (AEs) leading to premature discontinuation of study drug, or
- Any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug.
- An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily had a causal relationship with the treatment. The severity of the AEs was graded using the division of AIDS (DAIDS) toxicity grading scale version 2.1. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines : Grade 1 indicates a mild event, Grade 2 indicates a moderate event, Grade 3 indicates a severe event, Grade 4 indicates a potentially life-threatening event, Grade 5 indicates death. Percentages were rounded off.
Measured: Up to 165 weeks
Randomized Blinded Phase: Percentage of Participants With Grade 3 or Higher Laboratory Abnormalities
Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post-baseline visit, up to and including the last exposure date for participants who permanently discontinued study drug, or the last available date in the database snapshot for participants who were still on treatment at the time of an analysis. The DAIDS Toxicity Grading Scale, Version 2.1 was used to assign toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 included all values that do not meet the criteria for an abnormality of at least Grade 1. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 potentially life-threatening. Percentages were rounded off.
Measured: Up to 165 weeks

Timeline

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

30 Aug 2021Jan 2028

First posted6 Aug 2021
Study start30 Aug 2021
Primary completion27 May 2024
Study completionJan 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 5,368 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04994509
Sponsor's protocol ID: GS-US-412-5624
Other IDs: DOH-27- 072021-6125, 2023-001024-42, 2023
Acronym: PURPOSE 1
Status last verified: Oct 2026
First submitted: 2 Aug 2021
Last updated: 16 Oct 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Bekker LG, Das M, Abdool Karim Q, Ahmed K, Batting J, Brumskine W, Gill K, Harkoo I, Jaggernath M, Kigozi G, Kiwanuka N, Kotze P, Lebina L, Louw CE, Malahleha M, Manentsa M, Mansoor LE, Moodley D, Naicker V, Naidoo L, Naidoo M, Nair G, Ndlovu N, Palanee-Phillips T, Panchia R, Pillay S, Potloane D, Selepe P, Singh N, Singh Y, Spooner E, Ward AM, Zwane Z, Ebrahimi R, Zhao Y, Kintu A, Deaton C, Carter CC, Baeten JM, Matovu Kiweewa F; PURPOSE 1 Study Team. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. N Engl J Med. 2024 Oct 3;391(13):1179-1192. doi: 10.1056/NEJMoa2407001. Epub 2024 Jul 24.
PubMed 39046157

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

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RecruitingObservational study
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All Pre-Exposure Prophylaxis of HIV Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Double-Blinded, Multicenter, Randomized Study to Evaluate Safety and Efficacy of Twice Yearly Long-Acting Subcutaneous Lenacapavir, and Daily Oral Emtricitabine/Tenofovir Alafenamide for Pre-Exposure Prophylaxis in Adolescent Girls and Young Women at Risk of HIV Infection
ClinicalTrials.gov ID: NCT04994509
Acronym / sponsor ID: PURPOSE 1 / GS-US-412-5624
Conditions: Pre-Exposure Prophylaxis of HIV Infection
Phase: Phase 3
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 5,368 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 30 Aug 2021 (actual)
Primary completion: 27 May 2024 (actual)
Study completion: Jan 2028 (estimated)
First posted: 6 Aug 2021 (actual)
Results: Posted 19 Jun 2025

Clinical summary

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

The primary objective of this study is to evaluate the efficacy of LEN and F/TAF for HIV-1 PrEP in AGYW at risk of HIV-1 infection.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
Randomized Blinded Phase: Lenacapavir	Experimental	Drug: Oral Lenacapavir (LEN), Drug: Subcutaneous (SC) Lenacapavir (LEN), Drug: PTM F/TAF, Drug: PTM F/TDFParticipants will receive lenacapavir (LEN) 927 mg injection, every 26 weeks starting on Day 1 for up to approximately 52 weeks. Participants will also receive loading dose of LEN 600 mg, tablet, once daily on Day 1 and Day 2. Participants will receive placebo to match (PTM) emtricitabine/tenofovir disoproxil fumarate (F/TDF) or PTM emtricitabine/tenofovir alafenamide (F/TAF), once daily, up to approximately 52 weeks.
Randomized Blinded Phase: F/TAF	Experimental	Drug: F/TAF, Drug: Placebo SC LEN, Drug: PTM Oral LENParticipants will receive F/TAF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks, starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2.
Randomized Blinded Phase: F/TDF	Experimental	Drug: F/TDF, Drug: Placebo SC LEN, Drug: PTM Oral LENParticipants will receive F/TDF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2.
LEN Open-Label Extension (OLE) Phase	Experimental	Drug: Oral Lenacapavir (LEN), Drug: Subcutaneous (SC) Lenacapavir (LEN)After completion of the Blinded phase, participants will be offered entry into the LEN OLE Phase. Participants randomized to LEN will continue to receive LEN 927 mg injection, every 26 weeks until LEN becomes available or the sponsor elects to discontinue the study, whichever occurs first. Participants randomized to F/TAF or F/TDF will receive LEN 927 mg injection on OLE Day 1, Week 26, and every 26 weeks thereafter. Participants will also receive LEN 600 mg tablet on OLE Days 1 and 2.
Pharmacokinetic (PK) Tail Coverage Phase	Experimental	Drug: F/TDFParticipants who prematurely discontinue study drug in the randomized blinded phase will transition into the PK Tail Coverage phase. Participants will receive F/TDF, once daily, for 78 weeks beginning 26 weeks after the last LEN injection.

Who may qualify

Ages: 16 to 25 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (7 listed)

Incidence Phase
Randomized Phase

Key exclusion criteria (3 listed)

Prior receipt of an HIV vaccine.
Prior use of any long-acting systemic HIV pre-exposure prophylaxis (PrEP) or prior HIV postexposure prophylaxis (PEP) in the past 12 weeks.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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
Oral Lenacapavir (LEN)Also: GS-6207Tablets administered orally without regard to food	Drug	LEN Open-Label Extension (OLE) Phase, Randomized Blinded Phase: Lenacapavir
Subcutaneous (SC) Lenacapavir (LEN)Also: GS-6207, Yeztugo®, Yeytuo®Administered via SC injections	Drug	LEN Open-Label Extension (OLE) Phase, Randomized Blinded Phase: Lenacapavir
F/TAFAlso: Descovy®Tablets administered orally	Drug	Randomized Blinded Phase: F/TAF
F/TDFAlso: Truvada®Tablets administered orally	Drug	Pharmacokinetic (PK) Tail Coverage Phase, Randomized Blinded Phase: F/TDF
Placebo SC LENAdministered via SC injections	Drug	Randomized Blinded Phase: F/TAF, Randomized Blinded Phase: F/TDF
PTM Oral LENTablets administered orally	Drug	Randomized Blinded Phase: F/TAF, Randomized Blinded Phase: F/TDF
PTM F/TAFTablets administered orally	Drug	Randomized Blinded Phase: Lenacapavir
PTM F/TDFTablets administered orally	Drug	Randomized Blinded Phase: Lenacapavir

Primary outcome

Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY)
Time frame: Incidence Phase Screening Visit (Day 1)
bHIV per 100 PY in the Incidence Phase was calculated using RITA. The RITA incorporated HIV-1 testing results and recency assay testing results to estimate the bHIV. Recency assay testing was performed for participants in the All Screened Set found to have HIV-1 infection at the Incidence Phase Screening Visit as defined below. Participants were considered to have recent HIV-1 infection if the normalized optical density (ODn) was below 1.5 threshold using the Sedia limiting antigen avidity enzyme immunoassay (LAg-EIA) and the HIV-1 RNA (viral load) was > 75 copies/mL of blood. HIV-1 infection was defined as participants having at least one of the following central lab results at the Incidence Phase screening visit: * Positive HIV-1/2 differentiation Ab, OR * Positive HIV-1 ribonucleic acid (RNA) qualitative test, OR * HIV-1 RNA quantitative test ≥200 copies/mL.
Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN and F/TAF Compared to Participants in All Screened Set
Time frame: When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)
HIV-1 incidence per 100 PY for LEN and F/TAF was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses. HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples. bHIV incidence per 100 PY in All Screened Set was estimated as described in outcome measure#1.

5 secondary outcomes

Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN, F/TAF and F/TDF
Time frame: When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)
Randomized Blinded Phase: HIV-1 Incidence Among Participants Adherent to LEN
Time frame: When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)
Randomized Blinded Phase: Percentage of Participants Adherent to F/TAF in HIV-1 Diagnosed Participants and Their Matched Controls
Time frame: When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)
Randomized Blinded Phase: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to 165 weeks
Randomized Blinded Phase: Percentage of Participants With Grade 3 or Higher Laboratory Abnormalities
Time frame: Up to 165 weeks

Results and safety

Results posted to the registry on 19 Jun 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Randomized Blinded Phase: Lenacapavir	2,148	1,900
Randomized Blinded Phase: F/TAF	2,147	1,853
Randomized Blinded Phase: F/TDF	1,073	898
Open-Label Extension (OLE) Phase: LEN	0	0
OLE Phase: F/TAF	0	0
OLE Phase: F/TDF	0	0

Primary outcome: Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY)

Time frame: Incidence Phase Screening Visit (Day 1). Number (95% Confidence Interval). Unit: HIV-1 events per 100 person-years

Measure	Participants Screened for HIV-1 in Incidence Phase n = 8094
Value	2.407 (1.815 to 3.191)

Population analysed: Participants in the All Screened Set were analyzed. The All Screened Set included all participants who were screened for HIV-1 in the Incidence Phase and had a non-missing HIV-1 diagnosis based on HIV test results at Incidence Phase screening. As the outcome measure was assessed prior to Randomized Blinded Phase, the data is reported in one arm consisting of all participants screened in Incidence Phase.

Primary outcome: Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN and F/TAF Compared to Participants in All Screened Set

Time frame: When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks). Number (95% Confidence Interval). Unit: HIV-1 events per 100 person-years

Measure	Randomized Blinded Phase: Lenacapavir n = 2134	Randomized Blinded Phase: F/TAF n = 2136	Incidence Phase: All Screened Participants With Non-missing HIV-1 Diagnosis n = 8094
Value	0.000 (0.000 to 0.190)	2.018 (1.435 to 2.759)	2.407 (1.815 to 3.191)

Randomized Blinded Phase: Lenacapavir vs Incidence Phase: All Screened Participants With Non-missing HIV-1 Diagnosis: Rate Ratio: 0.000 (95% CI 0.000 to 0.042), p <0.0001, Likelihood ratio test
Randomized Blinded Phase: Lenacapavir vs Incidence Phase: All Screened Participants With Non-missing HIV-1 Diagnosis: Rate Ratio: 0.000 (95% CI 0.000 to 0.042), p <0.0001, Likelihood ratio test
Randomized Blinded Phase: F/TAF vs Incidence Phase: All Screened Participants With Non-missing HIV-1 Diagnosis: Rate Ratio: 0.839 (95% CI 0.550 to 1.279), p = 0.20697, Wald test

Population analysed: Participants in the LEN and F/TAF groups in the Full Analysis Set (FAS) were analyzed. The FAS included all randomized participants who received at least 1 dose of any study drug and had not been diagnosed with HIV-1 on or prior to the first dose date. Participants were analyzed as randomized. Per prespecified analysis, HIV-1 incidence for this outcome measure was reported only for participants who received LEN and F/TAF. The HIV-1 incidence was compared with participants in All Screened Set.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-Cause Mortality: Up to 165 Weeks; Adverse Events: Up to 165 Weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Randomized Blinded Phase: Lenacapavir	81 of 2,140 (3.8%)	1,827 of 2,140 (85.4%)	0 of 2,148
Randomized Blinded Phase: F/TAF	105 of 2,135 (4.9%)	1,646 of 2,135 (77.1%)	7 of 2,147
Randomized Blinded Phase: F/TDF	44 of 1,070 (4.1%)	794 of 1,070 (74.2%)	1 of 1,073

Limitations and caveats (from the sponsor): Due to data monitoring committee recommendation to stop the study early if the prespecified evaluation criteria were met, this is the date by when at least 50% of the participants were followed up for at least 52 weeks in the study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 39046157Bekker LG, Das M, Abdool Karim Q, Ahmed K, Batting J, Brumskine W, Gill K, Harkoo I, Jaggernath M, Kigozi G, Kiwanuka N, Kotze P, Lebina L, Louw CE, Malahleha M, Manentsa M, Mansoor LE, Moodley D, Naicker V, Naidoo L, Naidoo M, Nair G, Ndlovu N, Palanee-Phillips T, Panchia R, Pillay S, Potloane D, Selepe P, Singh N, Singh Y, Spooner E, Ward AM, Zwane Z, Ebrahimi R, Zhao Y, Kintu A, Deaton C, Carter CC, Baeten JM, Matovu Kiweewa F; PURPOSE 1 Study Team. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. N Engl J Med. 2024 Oct 3;391(13):1179-1192. doi: 10.1056/NEJMoa2407001. Epub 2024 Jul 24.
Gilead Clinical Trials WebsiteLink provided by the sponsor.
Individual participant dataSharing planned: No

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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

28 sites in 2 countries: 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 7 inclusion and 3 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 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in South Africa, Uganda. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY) (time frame: Incidence Phase Screening Visit (Day 1)). The study lists 2 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 NCT04994509, 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 16 Oct 2026.