Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection (PURPOSE 1)

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 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).

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 Overview

• Status: Active, not recruiting
• Conditions: Pre-Exposure Prophylaxis of HIV Infection
• Intervention / Treatment: Drug: Oral Lenacapavir (LEN); Drug: Subcutaneous (SC) Lenacapavir (LEN); Drug: PTM F/TAF; Drug: PTM F/TDF; Drug: F/TAF; Drug: Placebo SC LEN; Drug: PTM Oral LEN; Drug: F/TDF

• Study Type: Interventional
• Enrollment (Actual): 5368
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Randomized Blinded Phase: Lenacapavir; 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.	Drug: Oral Lenacapavir (LEN); Tablets administered orally without regard to food; Other Names: GS-6207; Drug: Subcutaneous (SC) Lenacapavir (LEN); Administered via SC injections; Other Names: GS-6207; Yeztugo®; Yeytuo®; Drug: PTM F/TAF; Tablets administered orally; Drug: PTM F/TDF; Tablets administered orally
Experimental: Randomized Blinded Phase: F/TAF; 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.	Drug: F/TAF; Tablets administered orally; Other Names: Descovy®; Drug: Placebo SC LEN; Administered via SC injections; Drug: PTM Oral LEN; Tablets administered orally
Experimental: Randomized Blinded Phase: F/TDF; 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.	Drug: Placebo SC LEN; Administered via SC injections; Drug: PTM Oral LEN; Tablets administered orally; Drug: F/TDF; Tablets administered orally; Other Names: Truvada®
Experimental: LEN Open-Label Extension (OLE) Phase; 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.	Drug: Oral Lenacapavir (LEN); Tablets administered orally without regard to food; Other Names: GS-6207; Drug: Subcutaneous (SC) Lenacapavir (LEN); Administered via SC injections; Other Names: GS-6207; Yeztugo®; Yeytuo®
Experimental: Pharmacokinetic (PK) Tail Coverage Phase; 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.	Drug: F/TDF; Tablets administered orally; Other Names: Truvada®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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 are 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.	When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 3 years)
Randomized Blinded Phase: Percentage of Participants Experiencing Clinically Significant 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.	When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 3 years)
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.	When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General 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.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2021
• Primary Completion (Actual): May 27, 2024
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 2, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Immune System Diseases; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Infections; Communicable Diseases; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Therapeutics; Drug Administration Routes; Drug Therapy; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Organophosphorus Compounds; Nucleosides; Deoxyribonucleosides; Organophosphonates; Adenine; Drug Combinations; Tenofovir; Emtricitabine; Injections; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; lenacapavir; Injections, Subcutaneous; emtricitabine tenofovir alafenamide
• Other Study ID Numbers: GS-US-412-5624; DOH-27- 072021-6125 (Registry Identifier: South African National Clinical Trial Registry)

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