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

NCT ID: NCT02842086

Last Updated: 2025-11-13

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

5399 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-02

Study Completion Date

2027-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Pre-Exposure Prophylaxis of HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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F/TAF

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

Group Type EXPERIMENTAL

F/TAF

Intervention Type DRUG

200/25 mg tablet administered orally once daily

F/TDF Placebo

Intervention Type DRUG

Tablet administered orally once daily

F/TDF

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

Group Type EXPERIMENTAL

F/TDF

Intervention Type DRUG

200/300 mg tablet administered orally once daily

F/TAF Placebo

Intervention Type DRUG

Tablet administered orally once daily

Open-label

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.

Group Type EXPERIMENTAL

F/TAF

Intervention Type DRUG

200/25 mg tablet administered orally once daily

Open-Label Extension

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.

Group Type EXPERIMENTAL

F/TAF

Intervention Type DRUG

200/25 mg tablet administered orally once daily

Interventions

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F/TAF

200/25 mg tablet administered orally once daily

Intervention Type DRUG

F/TDF

200/300 mg tablet administered orally once daily

Intervention Type DRUG

F/TAF Placebo

Tablet administered orally once daily

Intervention Type DRUG

F/TDF Placebo

Tablet administered orally once daily

Intervention Type DRUG

Other Intervention Names

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Descovy® Truvada®

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* Grade 3 or Grade 4 proteinuria or glycosuria that is unexplained or not clinically manageable.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Beverly Hills, California, United States

Site Status

Los Angeles, California, United States

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Los Angeles, California, United States

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Newport Beach, California, United States

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Oakland, California, United States

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Sacramento, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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San Francisco, California, United States

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San Francisco, California, United States

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Torrance, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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New Haven, Connecticut, United States

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

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

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Fort Lauderdale, Florida, United States

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Fort Lauderdale, Florida, United States

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Ft. Pierce, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Pensacola, Florida, United States

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West Palm Beach, Florida, United States

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Atlanta, Georgia, United States

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Atlanta, Georgia, United States

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Atlanta, Georgia, United States

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Macon, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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New Orleans, Louisiana, United States

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Boston, Massachusetts, United States

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Springfield, Massachusetts, United States

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Berkley, Michigan, United States

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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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Las Vegas, Nevada, United States

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Somers Point, New Jersey, United States

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Santa Fe, New Mexico, United States

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New York, New York, United States

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New York, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Chapel Hill, North Carolina, United States

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Huntersville, North Carolina, United States

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Cleveland, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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Seattle, Washington, United States

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Milwaukee, Wisconsin, United States

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Graz, , Austria

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Vienna, , Austria

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Hvidovre, Capital Region, Denmark

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Aarhus N, Central Jutland, Denmark

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Copenhagen, RegionH, Denmark

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Odense, , Denmark

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Nice, Alpe Maritimes, France

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Marseille, Provence-Alpes-Côte d'Azur Region, France

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Paris, Provence-Alpes-Côte d'Azur Region, France

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Paris, , France

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Munich, Bavaria, Germany

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Berlin, , Germany

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Berlin, , Germany

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Frankfurt, , Germany

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Dublin, Dublin, Ireland

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Dublin, , Ireland

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Milan, , Italy

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Roma, , Italy

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Amsterdam, , Netherlands

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Badalona, Barcelona, Spain

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Barcelona, , Spain

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Madrid, , Spain

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Vigo, , Spain

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Soho, London, United Kingdom

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Whitechapel, London, United Kingdom

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Edinburgh, Scotland, United Kingdom

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Brighton, Sussex, United Kingdom

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Birmingham, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Countries

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United States Austria Canada Denmark France Germany Ireland Italy Netherlands Spain United Kingdom

References

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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.

Reference Type 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.

Reference Type RESULT
PMID: 32711800 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39008999 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38312459 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37969014 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34197772 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34021709 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2022-501763-40

Identifier Type: OTHER

Identifier Source: secondary_id

2016-001399-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-412-2055

Identifier Type: -

Identifier Source: org_study_id