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 (DISCOVER)

April 14, 2026 updated by: Gilead Sciences

A Phase 3, Randomized, Double-blind 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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

5399

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8051
      • Vienna, Austria, 1090
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 2T1
    • Ontario
      • Toronto, Ontario, Canada, M5G 1K2
    • Quebec
      • Montreal, Quebec, Canada, H2l 4P9
      • Montreal, Quebec, Canada, H2W 1T8
      • Montreal, Quebec, Canada, H2L5B1
  • Denmark
      • Odense, Denmark, 5000
    • Capital Region
      • Hvidovre, Capital Region, Denmark, 2650
    • Central Jutland
      • Aarhus N, Central Jutland, Denmark, 8200
    • RegionH
      • Copenhagen, RegionH, Denmark, 2100
  • France
      • Paris, France, 75475
    • Alpe Maritimes
      • Nice, Alpe Maritimes, France, 6202
    • Provence
      • Marseille, Provence, France, 13006
      • Paris, Provence, France, 75020
  • Germany
      • Berlin, Germany, 10777
      • Berlin, Germany, 10439
      • Frankfurt, Germany, 60596
    • Bavaria
      • Munich, Bavaria, Germany, 81675
  • Ireland
      • Dublin, Ireland, 8
    • Dublin
      • Dublin, Dublin, Ireland, D07 A8NN
  • Italy
      • Milan, Italy, 20127
      • Roma, Italy, 00149
  • Netherlands
      • Amsterdam, Netherlands
  • Spain
      • Barcelona, Spain, 08015
      • Madrid, Spain, 28010
      • Vigo, Spain, 36312
    • Barcelona
      • Badalona, Barcelona, Spain, 08907
  • United Kingdom
      • Birmingham, United Kingdom, B9 5SS
      • London, United Kingdom, W2 1NY
      • London, United Kingdom, SE5 9RJ
      • London, United Kingdom, E9 6SR
      • London, United Kingdom, SE18 4QH
      • London, United Kingdom, WC1E 6JB
      • Manchester, United Kingdom, M13 0FH
    • London
      • Soho, London, United Kingdom, W1D 6AQ
      • Whitechapel, London, United Kingdom, E1 1BB
    • Scotland
      • Edinburgh, Scotland, United Kingdom, EH3 9HA
    • Sussex
      • Brighton, Sussex, United Kingdom, BN2 1ES
  • United States
    • California
      • Beverly Hills, California, United States, 90211
      • Los Angeles, California, United States, 90036
      • Los Angeles, California, United States, 90069
      • Newport Beach, California, United States, 92663
      • Oakland, California, United States, 94609
      • Sacramento, California, United States, 95817
      • Sacramento, California, United States, 95825
      • San Diego, California, United States, 92103
      • San Francisco, California, United States, 94118
      • San Francisco, California, United States, 94102
      • San Francisco, California, United States, 94103
      • Torrance, California, United States, 90502
    • Colorado
      • Aurora, Colorado, United States, 80045
      • Denver, Colorado, United States, 80209
    • Connecticut
      • New Haven, Connecticut, United States, 06510
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20009
      • Washington D.C., District of Columbia, United States, 20036
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
      • Fort Lauderdale, Florida, United States, 33316
      • Ft. Pierce, Florida, United States, 34982
      • Miami, Florida, United States, 33136
      • Orlando, Florida, United States, 32803
      • Pensacola, Florida, United States, 32504
      • West Palm Beach, Florida, United States, 33407
    • Georgia
      • Atlanta, Georgia, United States, 30308
      • Atlanta, Georgia, United States, 30309
      • Atlanta, Georgia, United States, 30312
      • Macon, Georgia, United States, 31201
    • Illinois
      • Chicago, Illinois, United States, 60612
      • Chicago, Illinois, United States, 60613
    • Louisiana
      • New Orleans, Louisiana, United States, 70119
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
      • Springfield, Massachusetts, United States, 01105
    • Michigan
      • Berkley, Michigan, United States, 48072
      • Detroit, Michigan, United States, 48202
    • Minnesota
      • Minneapolis, Minnesota, United States, 55415
    • Nevada
      • Las Vegas, Nevada, United States, 89104
    • New Jersey
      • Somers Point, New Jersey, United States, 08244
    • New Mexico
      • Santa Fe, New Mexico, United States, 87505
    • New York
      • New York, New York, United States, 10032
      • New York, New York, United States, 10029
      • New York, New York, United States, 10037
      • The Bronx, New York, United States, 10467
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7215
      • Huntersville, North Carolina, United States, 28078
    • Ohio
      • Cleveland, Ohio, United States, 44109
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
    • Texas
      • Austin, Texas, United States, 78705
      • Dallas, Texas, United States, 75246
      • Dallas, Texas, United States, 75208
      • Houston, Texas, United States, 77098
    • Washington
      • Seattle, Washington, United States, 98104
      • Seattle, Washington, United States, 98101
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Key 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

Key Exclusion Criteria

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

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: F/TAF
F/TAF+ F/TDF placebo for at least 96 weeks
Drug: F/TAF
200/25 mg tablet administered orally once daily
Other Names:
  • Descovy®
Drug: F/TDF Placebo
Tablet administered orally once daily
Experimental: F/TDF
F/TDF+ F/TAF placebo for at least 96 weeks
Drug: F/TDF
200/300 mg tablet administered orally once daily
Other Names:
  • Truvada®
Drug: F/TAF Placebo
Tablet administered orally once daily
Experimental: 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.
Drug: F/TAF
200/25 mg tablet administered orally once daily
Other Names:
  • Descovy®
Experimental: 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.
Drug: F/TAF
200/25 mg tablet administered orally once daily
Other Names:
  • Descovy®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of HIV-1 Infection Per 100 Person Years (PY)
Time Frame: 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)

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase
Time Frame: Baseline, Week 48
Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.
Baseline, Week 48
Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase
Time Frame: Baseline, Week 48
Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.
Baseline, Week 48
Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase
Time Frame: Baseline, Week 48

Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.

For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
Baseline, Week 48
Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase
Time Frame: Baseline, Week 48

Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.

For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
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
Time Frame: Baseline, Week 48
The UPCR was only calculated when corresponding UP ≥ 4.0 mg/dL. The UPCR "≤ 200 mg/g" category includes both participants with UP < 4.0 mg/dL and participants with UPCR ≤ 200 mg/g.
Baseline, Week 48
Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase
Time Frame: Baseline, Week 48
Baseline, Week 48
Incidence of HIV-1 Infection Per 100 PY
Time Frame: When all participants have 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 157 weeks)

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 have 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 157 weeks)
Percent Change From Baseline in Hip BMD at Week 96 in the Blinded Phase
Time Frame: Baseline, Week 96
Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.
Baseline, Week 96
Percent Change From Baseline in Spine BMD at Week 96 in the Blinded Phase
Time Frame: Baseline, Week 96
Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.
Baseline, Week 96
Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase
Time Frame: Baseline, Week 96

Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.

For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
Baseline, Week 96
Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase
Time Frame: Baseline, Week 96

Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.

For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
Baseline, Week 96
Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase
Time Frame: Baseline, Week 96
The UPCR was only calculated when corresponding UP ≥ 4.0 mg/dL. The UPCR "≤ 200 mg/g" category includes both participants with UP < 4.0 mg/dL and participants with UPCR ≤ 200 mg/g.
Baseline, Week 96
Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase
Time Frame: Baseline, Week 96
Baseline, Week 96
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)
First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)
Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality
Time Frame: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)
First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Investigators

  • Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 2, 2016

Primary Completion (Actual)

January 31, 2019

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

July 20, 2016

First Submitted That Met QC Criteria

July 20, 2016

First Posted (Estimated)

July 22, 2016

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

April 14, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-412-2055
  • 2016-001399-31 (EudraCT Number)
  • 2022-501763-40 (Other Identifier: European Medicines Agency)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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