F/TAF for HIV Pre-Exposure Prophylaxis

(DISCOVER Trial)

Recruiting at 73 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must be taking: Emtricitabine/tenofovir

Disqualifiers: Grade 3/4 proteinuria, glycosuria, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

5399 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug F/TAF for HIV prevention?

Research shows that the drug combination of emtricitabine and tenofovir alafenamide (F/TAF) is effective in preventing HIV, with studies indicating it is as effective as the older combination of emtricitabine and tenofovir disoproxil fumarate (F/TDF), but with better safety for kidneys and bones. ^{1 2 3 4 5}

Is F/TAF safe for use in humans?

F/TAF (Emtricitabine and Tenofovir Alafenamide) is considered to have an improved safety profile compared to the older version, F/TDF (Emtricitabine and Tenofovir Disoproxil Fumarate), particularly in terms of kidney and bone health. ^{1 2 3 5 6}

How is the drug F/TAF unique for HIV prevention?

F/TAF is unique because it uses tenofovir alafenamide (TAF), a newer form of tenofovir that delivers higher levels of the active drug inside cells and has a better safety profile compared to the older version, tenofovir disoproxil fumarate (TDF). This makes F/TAF a potentially safer option for preventing HIV. ^{1 2 3 6 7}

What is the purpose of this trial?

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.

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for men and transgender women who have sex with men, are at high risk of HIV-1 infection, and have had recent sexually transmitted infections or unprotected intercourse. Participants must be HIV negative with adequate blood cell counts, kidney function (eGFR ≥ 60 mL/min), liver function (AST/ALT ≤ 2.5 × ULN), and not have serious proteinuria or glycosuria.

Inclusion Criteria

My liver functions, including AST, ALT, and bilirubin levels, are within normal ranges.

I am a MSM or TGW and meet one of the specific criteria.

I've had unprotected sex with at least two men whose HIV status I don't fully know in the last 3 months.

Exclusion Criteria

I have severe kidney issues with protein or sugar in my urine that can't be managed.

There may be other requirements that need to be met in order to participate in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Blinded Treatment

Participants receive either F/TAF or F/TDF with a placebo for at least 96 weeks

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

48-96 weeks

Open-label Treatment

Participants are offered the option to continue on open-label F/TAF treatment for 96 weeks

96 weeks

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 for 408 weeks

408 weeks

Treatment Details

Interventions

• Emtricitabine
• Tenofovir Alafenamide

Trial Overview The study compares the effectiveness of two daily pre-exposure prophylaxis treatments to prevent HIV: Emtricitabine/Tenofovir Alafenamide (F/TAF) versus Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF). Participants will be followed for a minimum of 48 weeks, with half being monitored for up to 96 weeks after starting treatment.

Participant Groups

Group I: Open-label Experimental Treatment 1 Intervention

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 II: Open-Label Extension Experimental Treatment 1 Intervention

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 III: F/TDF Experimental Treatment 2 Interventions

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

Group IV: F/TAF Experimental Treatment 2 Interventions

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

Emtricitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Emtriva for:

• HIV-1 infections

Approved in United States as Emtriva for:

• HIV-1 infections
• Pre-exposure prophylaxis of HIV-1

Approved in Canada as Emtriva for:

• HIV-1 infections

Approved in Japan as Emtriva for:

• HIV-1 infections

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

In a comparison of tenofovir alafenamide and emtricitabine (TAF/FTC) versus placebo for HIV prevention, TAF/FTC showed a significant reduction in HIV infection risk, being 5.8 percentage points lower than placebo over 96 weeks.

The analysis utilized data from the DISCOVER and iPrEx trials, confirming that TAF/FTC is effective in preventing HIV infection, with a 12.5-fold lower risk compared to placebo after adjusting for demographic differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV prevention among men who have sex with men: tenofovir alafenamide combination preexposure prophylaxis versus placebo. Zivich, PN., Cole, SR., Edwards, JK., et al.[2023]

Tenofovir alafenamide-emtricitabine (F/TAF) is a safer option for HIV preexposure prophylaxis (PrEP) compared to tenofovir disoproxil fumarate-emtricitabine (F/TDF), with F/TAF potentially averting 2101 fractures and 25 cases of end-stage renal disease (ESRD) over five years for 123,610 men who have sex with men (MSM) using PrEP.

The maximum price that payers should be willing to pay for F/TAF over generic F/TDF is estimated at $8670 per year, reflecting its improved safety profile, which is valued at no more than an additional $370 per person per year when considering the cost-effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Pricing of Branded Tenofovir Alafenamide-Emtricitabine Relative to Generic Tenofovir Disoproxil Fumarate-Emtricitabine for HIV Preexposure Prophylaxis: A Cost-Effectiveness Analysis. Walensky, RP., Horn, T., McCann, NC., et al.[2021]

The combination of emtricitabine and tenofovir alafenamide (F/TAF) is shown to be as effective as the traditional F/TDF combination in preventing HIV acquisition, with some evidence suggesting it may be even more effective.

F/TAF has a better safety profile, particularly regarding kidney health, making it a potentially safer option for older individuals, although it is associated with weight gain and has not yet been tested for all routes of HIV exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the combination of emtricitabine/ tenofovir alafenamide fumarate to reduce the risk of sexually acquired HIV-1-infection in at-risk adults. Mesplède, T.[2022]

In a phase 3 study involving 5387 participants, daily emtricitabine and tenofovir alafenamide was found to be non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, with a lower incidence of HIV infections in the tenofovir alafenamide group (0.16 vs 0.34 infections per 100 person-years).

The tenofovir alafenamide regimen demonstrated better safety profiles, showing superior outcomes in bone mineral density and renal biomarkers compared to the tenofovir disoproxil fumarate regimen, with low rates of adverse events leading to discontinuation in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Mayer, KH., Molina, JM., Thompson, MA., et al.[2022]

The study found that the combination of emtricitabine and tenofovir alafenamide (F/TAF) was safe and well-tolerated among HIV-uninfected women, with significantly lower gastrointestinal side effects compared to the older F/TDF combination.

F/TAF demonstrated higher concentrations of the active form of tenofovir (TFV-DP) in peripheral blood mononuclear cells and vaginal tissues compared to F/TDF, suggesting it may be a more effective option for HIV pre-exposure prophylaxis in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of a Tenofovir Alafenamide Fumarate-Emtricitabine based Oral Antiretroviral Regimen for Prevention of HIV Acquisition in Women: A Randomized Controlled Trial. Thurman, AR., Schwartz, JL., Cottrell, ML., et al.[2022]

In a study involving macaques, the combination of tenofovir alafenamide (TAF) and emtricitabine (FTC) effectively prevented simian/human immunodeficiency virus (SHIV) infection, demonstrating its potential as a pre-exposure prophylaxis (PrEP) for HIV.

All control macaques were infected after exposure to SHIV, while all macaques treated with FTC/TAF remained protected, indicating strong efficacy of this treatment combination in preventing viral infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoprophylaxis With Oral Emtricitabine and Tenofovir Alafenamide Combination Protects Macaques From Rectal Simian/Human Immunodeficiency Virus Infection. Massud, I., Mitchell, J., Babusis, D., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

HIV prevention among men who have sex with men: tenofovir alafenamide combination preexposure prophylaxis versus placebo. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Comparative Pricing of Branded Tenofovir Alafenamide-Emtricitabine Relative to Generic Tenofovir Disoproxil Fumarate-Emtricitabine for HIV Preexposure Prophylaxis: A Cost-Effectiveness Analysis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Evaluating the combination of emtricitabine/ tenofovir alafenamide fumarate to reduce the risk of sexually acquired HIV-1-infection in at-risk adults. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide for Human Immunodeficiency Virus Preexposure Prophylaxis at a Boston Community Health Center. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of a Tenofovir Alafenamide Fumarate-Emtricitabine based Oral Antiretroviral Regimen for Prevention of HIV Acquisition in Women: A Randomized Controlled Trial. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Chemoprophylaxis With Oral Emtricitabine and Tenofovir Alafenamide Combination Protects Macaques From Rectal Simian/Human Immunodeficiency Virus Infection. [2021]