Study to Evaluate the Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/TAF) Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex With Men and Are At Risk of HIV-1 Infection

NCT02842086 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: GS-US-412-20552022-501763-402016-001399-31
• Study Type: interventional
• Target: 5,399
• Locations: 11 countries
• Sites: 93

Brief Summary

The primary objective of this study is to assess the rates of HIV-1 infection in Men (MSM) and transgender women (TGW) who have sex with men and who are administered daily emtricitabine/tenofovir alafenamide (F/TAF) or emtricitabine/tenofovir disoproxil fumarate (F/TDF) with a minimum follow-up of 48 weeks and at least 50% of participants have 96 weeks of follow-up after randomization.

Conditions

Pre-Exposure Prophylaxis of HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Incidence of HIV-1 Infection Per 100 Person Years (PY)

  The incidence of HIV-1 infection rate per 100 PY was calculated as the number of participants who became HIV infected during the study after the first dose of study drug divided by the sum of all participants' years (where a year is 365.25 days) of follow-up while at risk of HIV infection during the study. HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests performed via central lab or local lab: * Serologic evidence of seroconversion (reactive screening HIV Antigen/Antibody or Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated participants, or * Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or * Evidence of acute HIV-1 infection (reactive p24 Antigen or positive qualitative or quantitative RNA, in the absence of reactive HIV-1 Antibody results)

  When all participants completed minimum follow-up of 48 weeks and at least 50% of the participants completed 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 125 weeks)

Secondary Outcomes (15)

• Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase

  Baseline, Week 48

• Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase

  Baseline, Week 48

• Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase

  Baseline, Week 48

• Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase

  Baseline, Week 48

• Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase

  Baseline, Week 48

Study Arms (4)

F/TAF

EXPERIMENTAL

F/TAF+ F/TDF placebo for at least 96 weeks

Drug: F/TAF; Drug: F/TDF Placebo

F/TDF

EXPERIMENTAL

F/TDF+ F/TAF placebo for at least 96 weeks

Drug: F/TDF; Drug: F/TAF Placebo

Open-label

EXPERIMENTAL

Once all participants have been on blinded treatment for at least 96 weeks, the study will be unblinded and participants will be offered the option to continue on open-label F/TAF treatment for 96 weeks.

Drug: F/TAF

Open-Label Extension

EXPERIMENTAL

Participants who remain on study at Open-label Week 96 will have the option to continue on open-label F/TAF treatment in the Open-label extension phase for 408 weeks.

Drug: F/TAF

Interventions

F/TAF DRUG

200/25 mg tablet administered orally once daily

Also known as: Descovy®

F/TAF; Open-Label Extension; Open-label

F/TDF DRUG

200/300 mg tablet administered orally once daily

Also known as: Truvada®

F/TDF

F/TAF Placebo DRUG

Tablet administered orally once daily

F/TDF

F/TDF Placebo DRUG

Tablet administered orally once daily

F/TAF

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Men and Transgender Women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be at high risk of sexual acquisition of HIV
• HIV-1 negative status
• MSM and TGW (male at birth) who have at least one of the following:
• condomless anal intercourse with at least two unique male partners in the past 12 weeks (partners must be either HIV-infected or of unknown HIV status)
• documented history of syphilis in the past 24 weeks
• documented history of rectal gonorrhea or chlamydia in the past 24 weeks
• Adequate renal function: estimated glomerular filtration rate ≥ 60 mL/min according to the Cockcroft-Gault formula
• Adequate liver and hematologic function:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) and total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Absolute neutrophil count ≥ 1000/mm\^3; platelets ≥ 75,000/mm\^3; hemoglobin ≥ 10 g/dL

You may not qualify if:

• Grade 3 or Grade 4 proteinuria or glycosuria that is unexplained or not clinically manageable.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (93)

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Beverly Hills, California, 90211, United States

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Los Angeles, California, 90036, United States

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Los Angeles, California, 90069, United States

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Newport Beach, California, 92663, United States

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Oakland, California, 94609, United States

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Sacramento, California, 95817, United States

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Sacramento, California, 95825, United States

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San Diego, California, 92103, United States

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San Francisco, California, 94102, United States

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San Francisco, California, 94103, United States

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San Francisco, California, 94118, United States

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Torrance, California, 90502, United States

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Aurora, Colorado, 80045, United States

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Denver, Colorado, 80209, United States

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New Haven, Connecticut, 06510, United States

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Washington D.C., District of Columbia, 20009, United States

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Washington D.C., District of Columbia, 20036, United States

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Fort Lauderdale, Florida, 33308, United States

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Fort Lauderdale, Florida, 33316, United States

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Ft. Pierce, Florida, 34982, United States

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Miami, Florida, 33136, United States

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Orlando, Florida, 32803, United States

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Pensacola, Florida, 32504, United States

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West Palm Beach, Florida, 33407, United States

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Atlanta, Georgia, 30308, United States

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Atlanta, Georgia, 30309, United States

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Atlanta, Georgia, 30312, United States

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Macon, Georgia, 31201, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60613, United States

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New Orleans, Louisiana, 70119, United States

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Boston, Massachusetts, 02215, United States

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Springfield, Massachusetts, 01105, United States

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Berkley, Michigan, 48072, United States

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Detroit, Michigan, 48202, United States

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Minneapolis, Minnesota, 55415, United States

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Las Vegas, Nevada, 89104, United States

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Somers Point, New Jersey, 08244, United States

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Santa Fe, New Mexico, 87505, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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New York, New York, 10037, United States

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The Bronx, New York, 10467, United States

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Chapel Hill, North Carolina, 27599-7215, United States

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Huntersville, North Carolina, 28078, United States

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Cleveland, Ohio, 44109, United States

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Philadelphia, Pennsylvania, 19107, United States

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Austin, Texas, 78705, United States

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Dallas, Texas, 75208, United States

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Dallas, Texas, 75246, United States

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Houston, Texas, 77098, United States

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Seattle, Washington, 98101, United States

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Seattle, Washington, 98104, United States

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Milwaukee, Wisconsin, 53226, United States

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Graz, 8051, Austria

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Vienna, 1090, Austria

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Vancouver, British Columbia, V6Z 2T1, Canada

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Toronto, Ontario, M5G 1K2, Canada

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Montreal, Quebec, H2l 4P9, Canada

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Montreal, Quebec, H2L5B1, Canada

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Montreal, Quebec, H2W 1T8, Canada

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Hvidovre, Capital Region, 2650, Denmark

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Aarhus N, Central Jutland, 8200, Denmark

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Copenhagen, RegionH, 2100, Denmark

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Odense, 5000, Denmark

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Nice, Alpe Maritimes, 6202, France

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Marseille, Provence, 13006, France

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Paris, Provence, 75020, France

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Paris, 75475, France

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Munich, Bavaria, 81675, Germany

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Berlin, 10439, Germany

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Berlin, 10777, Germany

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Frankfurt, 60596, Germany

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Dublin, Dublin, D07 A8NN, Ireland

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Dublin, 8, Ireland

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Milan, 20127, Italy

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Roma, 00149, Italy

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Amsterdam, Netherlands

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Badalona, Barcelona, 08907, Spain

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Barcelona, 08015, Spain

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Madrid, 28010, Spain

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Vigo, 36312, Spain

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Soho, London, W1D 6AQ, United Kingdom

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Whitechapel, London, E1 1BB, United Kingdom

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Edinburgh, Scotland, EH3 9HA, United Kingdom

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Brighton, Sussex, BN2 1ES, United Kingdom

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Birmingham, B9 5SS, United Kingdom

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London, E9 6SR, United Kingdom

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London, SE18 4QH, United Kingdom

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London, SE5 9RJ, United Kingdom

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London, W2 1NY, United Kingdom

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London, WC1E 6JB, United Kingdom

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Manchester, M13 0FH, United Kingdom

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Related Publications (7)

• Hare B. The Phase 3 DISCOVER Study: Daily F/TAF or F/TDF for HIV Preexposure Prophylaxis [Presentation]. Conference on Retroviruses and Opportunistic Infections (CROI); 2019 04-07 March; Seattle, WA.

  RESULT

• Mayer KH, Molina JM, Thompson MA, Anderson PL, Mounzer KC, De Wet JJ, DeJesus E, Jessen H, Grant RM, Ruane PJ, Wong P, Ebrahimi R, Zhong L, Mathias A, Callebaut C, Collins SE, Das M, McCallister S, Brainard DM, Brinson C, Clarke A, Coll P, Post FA, Hare CB. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet. 2020 Jul 25;396(10246):239-254. doi: 10.1016/S0140-6736(20)31065-5.

  PMID: 32711800 RESULT

• Wohl DA, Spinner CD, Flamm J, Hare CB, Doblecki-Lewis S, Ruane PJ, Molina JM, Mills A, Brinson C, Ramgopal M, Clarke A, Crofoot G, Martorell C, Carter C, Cox S, Hojilla JC, Shao Y, Das M, Kintu A, Baeten JM, Grant RM, Mounzer K, Mayer K. HIV-1 infection kinetics, drug resistance, and long-term safety of pre-exposure prophylaxis with emtricitabine plus tenofovir alafenamide (DISCOVER): week 144 open-label extension of a randomised, controlled, phase 3 trial. Lancet HIV. 2024 Aug;11(8):e508-e521. doi: 10.1016/S2352-3018(24)00130-9. Epub 2024 Jul 14.

  PMID: 39008999 DERIVED

• Cespedes MS, Das M, Yager J, Prins M, Krznaric I, de Jong J, Xiao D, Shao Y, Wong P, Kintu A, Carter C, Hoornenborg E, Ruane P, Phoenix J, Younis I, Halperin J. Gender Affirming Hormones Do Not Affect the Exposure and Efficacy of F/TDF or F/TAF for HIV Preexposure Prophylaxis: A Subgroup Analysis from the DISCOVER Trial. Transgend Health. 2024 Jan 31;9(1):46-52. doi: 10.1089/trgh.2022.0048. eCollection 2024 Feb.

  PMID: 38312459 DERIVED

• Zivich PN, Cole SR, Edwards JK, Glidden DV, Das M, Shook-Sa BE, Shao Y, Mehrotra ML, Adimora AA, Eron JJ. HIV Prevention Among Men Who Have Sex With Men: Tenofovir Alafenamide Combination Preexposure Prophylaxis Versus Placebo. J Infect Dis. 2024 Apr 12;229(4):1123-1130. doi: 10.1093/infdis/jiad507.

  PMID: 37969014 DERIVED

• Ogbuagu O, Ruane PJ, Podzamczer D, Salazar LC, Henry K, Asmuth DM, Wohl D, Gilson R, Shao Y, Ebrahimi R, Cox S, Kintu A, Carter C, Das M, Baeten JM, Brainard DM, Whitlock G, Brunetta JM, Kronborg G, Spinner CD; DISCOVER study team. Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet HIV. 2021 Jul;8(7):e397-e407. doi: 10.1016/S2352-3018(21)00071-0.

  PMID: 34197772 DERIVED

• Glidden DV, Das M, Dunn DT, Ebrahimi R, Zhao Y, Stirrup OT, Baeten JM, Anderson PL. Using the adherence-efficacy relationship of emtricitabine and tenofovir disoproxil fumarate to calculate background hiv incidence: a secondary analysis of a randomized, controlled trial. J Int AIDS Soc. 2021 May;24(5):e25744. doi: 10.1002/jia2.25744.

  PMID: 34021709 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

emtricitabine tenofovir alafenamide; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: July 22, 2016
• Study Start: September 2, 2016
• Primary Completion: January 31, 2019
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 5, 2026
• Results First Posted: March 17, 2020

Record last verified: 2026-04

Locations

IT (2); ES (4); GB (11); FR (4); DE (4); AU (2); NL (1); DK (4); CA (5); US (54); IE (2)