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AzTrials

Pre-Exposure Prophylaxis of HIV-1 InfectionPhase 3DISCOVERNCT02842086

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

A Phase 3 study testing F/TAF and F/TDF in people with Pre-Exposure Prophylaxis of HIV-1 Infection, run by Gilead Sciences at 93 sites in 11 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
F/TAF and F/TDF
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
5,399 participants
Where
93 sitesin 11 countries
Study dates
2 Sep 2016to 29 Jul 2026
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 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • Grade 3 or Grade 4 proteinuria or glycosuria that is unexplained or not clinically manageable.
  • NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Trial locations and contacts

93 sites in 11 countries.

93 sites in 11 countries

United States54 sites

  • Study site

    Atlanta, Georgia, 30308

  • Study site

    Atlanta, Georgia, 30309

  • Study site

    Atlanta, Georgia, 30312

  • Study site

    Aurora, Colorado, 80045

  • Study site

    Austin, Texas, 78705

  • Study site

    Berkley, Michigan, 48072

  • Study site

    Beverly Hills, California, 90211

  • Study site

    Boston, Massachusetts, 02215

  • Study site

    Chapel Hill, North Carolina, 27599-7215

  • Study site

    Chicago, Illinois, 60612

  • Study site

    Chicago, Illinois, 60613

  • Study site

    Cleveland, Ohio, 44109

  • Study site

    Dallas, Texas, 75208

  • Study site

    Dallas, Texas, 75246

  • Study site

    Denver, Colorado, 80209

  • Study site

    Detroit, Michigan, 48202

  • Study site

    Fort Lauderdale, Florida, 33308

  • Study site

    Fort Lauderdale, Florida, 33316

  • Study site

    Ft. Pierce, Florida, 34982

  • Study site

    Houston, Texas, 77098

  • Study site

    Huntersville, North Carolina, 28078

  • Study site

    Las Vegas, Nevada, 89104

  • Study site

    Los Angeles, California, 90036

  • Study site

    Los Angeles, California, 90069

  • Study site

    Macon, Georgia, 31201

  • Study site

    Miami, Florida, 33136

  • Study site

    Milwaukee, Wisconsin, 53226

  • Study site

    Minneapolis, Minnesota, 55415

  • Study site

    New Haven, Connecticut, 06510

  • Study site

    New Orleans, Louisiana, 70119

  • Study site

    New York, New York, 10029

  • Study site

    New York, New York, 10032

  • Study site

    New York, New York, 10037

  • Study site

    Newport Beach, California, 92663

  • Study site

    Oakland, California, 94609

  • Study site

    Orlando, Florida, 32803

  • Study site

    Pensacola, Florida, 32504

  • Study site

    Philadelphia, Pennsylvania, 19107

  • Study site

    Sacramento, California, 95817

  • Study site

    Sacramento, California, 95825

  • Study site

    San Diego, California, 92103

  • Study site

    San Francisco, California, 94102

  • Study site

    San Francisco, California, 94103

  • Study site

    San Francisco, California, 94118

  • Study site

    Santa Fe, New Mexico, 87505

  • Study site

    Seattle, Washington, 98101

  • Study site

    Seattle, Washington, 98104

  • Study site

    Somers Point, New Jersey, 08244

  • Study site

    Springfield, Massachusetts, 01105

  • Study site

    The Bronx, New York, 10467

  • Study site

    Torrance, California, 90502

  • Study site

    Washington D.C., District of Columbia, 20009

  • Study site

    Washington D.C., District of Columbia, 20036

  • Study site

    West Palm Beach, Florida, 33407

Other trials in United States

United Kingdom11 sites

  • Study site

    Birmingham, B9 5SS

  • Study site

    Brighton, Sussex, BN2 1ES

  • Study site

    Edinburgh, Scotland, EH3 9HA

  • Study site

    London, E9 6SR

  • Study site

    London, SE18 4QH

  • Study site

    London, SE5 9RJ

  • Study site

    London, W2 1NY

  • Study site

    London, WC1E 6JB

  • Study site

    Manchester, M13 0FH

  • Study site

    Soho, London, W1D 6AQ

  • Study site

    Whitechapel, London, E1 1BB

Other trials in United Kingdom

Canada5 sites

  • Study site

    Montreal, Quebec, H2l 4P9

  • Study site

    Montreal, Quebec, H2L5B1

  • Study site

    Montreal, Quebec, H2W 1T8

  • Study site

    Toronto, Ontario, M5G 1K2

  • Study site

    Vancouver, British Columbia, V6Z 2T1

Other trials in Canada

Denmark4 sites

  • Study site

    Aarhus N, Central Jutland, 8200

  • Study site

    Copenhagen, RegionH, 2100

  • Study site

    Hvidovre, Capital Region, 2650

  • Study site

    Odense, 5000

Other trials in Denmark

France4 sites

  • Study site

    Marseille, Provence, 13006

  • Study site

    Nice, Alpe Maritimes, 6202

  • Study site

    Paris, Provence, 75020

  • Study site

    Paris, 75475

Other trials in France

Germany4 sites

  • Study site

    Berlin, 10439

  • Study site

    Berlin, 10777

  • Study site

    Frankfurt, 60596

  • Study site

    Munich, Bavaria, 81675

Other trials in Germany

Spain4 sites

  • Study site

    Badalona, Barcelona, 08907

  • Study site

    Barcelona, 08015

  • Study site

    Madrid, 28010

  • Study site

    Vigo, 36312

Other trials in Spain

Austria2 sites

  • Study site

    Graz, 8051

  • Study site

    Vienna, 1090

Other trials in Austria

Ireland2 sites

  • Study site

    Dublin, Dublin, D07 A8NN

  • Study site

    Dublin, 8

Other trials in Ireland

Italy2 sites

  • Study site

    Milan, 20127

  • Study site

    Roma, 00149

Other trials in Italy

Netherlands1 site

  • Study site

    Amsterdam

Other trials in Netherlands

About this study

Official title: 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.

Being tested
F/TAF, F/TDF, F/TAF Placebo, F/TDF Placebo

What participants receive

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

  • F/TAFDrug

    Also called Descovy®

    200/25 mg tablet administered orally once daily

  • F/TDFDrug

    Also called Truvada®

    200/300 mg tablet administered orally once daily

  • F/TAF PlaceboDrug

    Tablet administered orally once daily

  • F/TDF PlaceboDrug

    Tablet administered orally once daily

Study groups in NCT02842086
Study groupRoleWhat they receive
F/TAFExperimentalF/TAF+ F/TDF placebo for at least 96 weeks
Receives: Drug: F/TAF; Drug: F/TDF Placebo
F/TDFExperimentalF/TDF+ F/TAF placebo for at least 96 weeks
Receives: Drug: F/TDF; Drug: F/TAF Placebo
Open-labelExperimentalOnce 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.
Receives: Drug: F/TAF
Open-Label ExtensionExperimentalParticipants 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.
Receives: Drug: F/TAF

What is being measured

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

  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)

    Measured: 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)

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

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

    Measured: Baseline, Week 48

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

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

    Measured: Baseline, Week 48

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

    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.

    Measured: Baseline, Week 48

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

    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.

    Measured: Baseline, Week 48

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

    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.

    Measured: Baseline, Week 48

  6. Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase

    Measured: Baseline, Week 48

  7. Incidence of HIV-1 Infection Per 100 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)

    Measured: When all participants have 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 157 weeks)

  8. Percent Change From Baseline in Hip BMD at Week 96 in the Blinded Phase

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

    Measured: Baseline, Week 96

  9. Percent Change From Baseline in Spine BMD at Week 96 in the Blinded Phase

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

    Measured: Baseline, Week 96

  10. Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase

    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.

    Measured: Baseline, Week 96

  11. Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase

    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.

    Measured: Baseline, Week 96

  12. Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase

    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.

    Measured: Baseline, Week 96

  13. Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase

    Measured: Baseline, Week 96

  14. Percentage of Participants Experiencing Treatment-Emergent Adverse Events

    Measured: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)

  15. Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality

    Measured: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)

Timeline

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

  1. First posted22 Jul 2016 (estimated)
  2. Study start2 Sep 2016
  3. Primary completion31 Jan 2019
  4. Study completion29 Jul 2026

Why it stopped: Following review of accumulated safety data from DISCOVER and real-world use of F/TAF, the sponsor determined that the long-term safety of F/TAF had been demonstrated and no further safety monitoring within the study was required.

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
5,399 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02842086
Sponsor's protocol ID
GS-US-412-2055
Other IDs
2022-501763-40, 2016-001399-31, 2016
Acronym
DISCOVER
Status last verified
Aug 2026
First submitted
20 Jul 2016
Last updated
8 Sep 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified external researchers may request IPD for this study. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment

Publications

  • 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.

  • 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.

    PubMed 32711800

  • 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.

    PubMed 39008999

  • 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.

    PubMed 38312459

  • 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.

    PubMed 37969014

  • 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.

    PubMed 34197772

  • 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.

    PubMed 34021709

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing F/TAF and F/TDF in people with Pre-Exposure Prophylaxis of HIV-1 Infection, run by Gilead Sciences at 93 sites in 11 countries.

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 10 inclusion and 2 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: stopped early, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 93 sites in United States, United Kingdom, Canada, Denmark, France and 6 more countries. 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 17 Mar 2020). 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 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)). 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 NCT02842086, which also lists 7 linked publications.

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 8 Sep 2026.

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