F/TAF for HIV Pre-Exposure Prophylaxis

(DISCOVER Trial)

Not currently recruiting at 76 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two medications, F/TAF (Emtricitabine and Tenofovir Alafenamide) and F/TDF, to prevent HIV infection in men and transgender women who have sex with men. Researchers aim to determine how effectively these treatments reduce new HIV cases over time. Participants will be randomly assigned to receive either F/TAF with a placebo or F/TDF with a placebo for at least 96 weeks, with the option to continue with F/TAF for a longer period if desired. The study seeks HIV-negative individuals at high risk, such as those who have recently engaged in condomless sex with multiple partners or have a history of certain sexually transmitted infections. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking HIV prevention method.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that the combination of emtricitabine and tenofovir alafenamide, known as F/TAF, is safe and effective for long-term use in preventing HIV in men and transgender women who have sex with men. Research indicates that F/TAF is generally well-tolerated, with many participants remaining HIV-negative during trials.

Another treatment, emtricitabine and tenofovir disoproxil fumarate (F/TDF), has also been tested and used for HIV prevention. Both treatments have been thoroughly studied and are approved for reducing the risk of HIV, indicating their safety for people at risk.

While no treatment is without side effects, evidence so far shows that F/TAF and F/TDF are both effective and have manageable side effects for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about F/TAF for HIV pre-exposure prophylaxis because it combines emtricitabine and tenofovir alafenamide, a newer formulation known for its improved safety profile, particularly on kidney and bone health, compared to the older tenofovir disoproxil fumarate (TDF). Unlike TDF, which is commonly used in existing treatments, tenofovir alafenamide is absorbed more efficiently and requires a lower dose, minimizing potential side effects. This could make F/TAF a more appealing option for long-term use in preventing HIV, offering a promising advancement over current options.

What evidence suggests that this trial's treatments could be effective for HIV prevention?

This trial will compare F/TAF and F/TDF for HIV pre-exposure prophylaxis. Studies have shown that both F/TAF and F/TDF effectively prevent HIV infection. Specifically, the DISCOVER trial, which included over 5,300 participants, found that 99.7% of people remained HIV negative when using F/TAF as a prevention method. Meanwhile, F/TDF has been shown to reduce the risk of HIV by nearly 90% when taken regularly, proving especially effective for men who have sex with men (MSM). Both treatments are widely recognized and considered safe for long-term use in preventing HIV. ^{1 2 6 7 8}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34197772/

Long-term safety and efficacy of emtricitabine and tenofovir ... Interpretation: Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02842086

NCT02842086 | Study to Evaluate the Safety and Efficacy ... 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.

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2809151

Use of Tenofovir Alafenamide Fumarate for HIV Pre ... In this study of people taking PrEP, TAF use was found to be associated with higher incident hypertension and statin initiation compared with TDF use.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12492902/

Long-term safety and efficacy of emtricitabine and tenofovir ... Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with ...

5. descovyhcp.com descovyhcp.com/discover-clinical-trial

99.7% remained HIV negative with DESCOVY ®1,2 Proven prevention with powerful results: 99.7% remained HIV negative with DESCOVY · DISCOVER is the largest PrEP clinical trial, with over 5300 participants ...

6. descovy.com descovy.com/

DESCOVY for PrEP® (pre-exposure prophylaxis) Learn about DESCOVY® (emtricitabine and tenofovir alafenamide) for PrEP (pre-exposure prophylaxis) ... *Similarly, 99.4% stayed HIV-negative with TRUVADA ®.

7. gilead.com gilead.com/-/media/files/pdfs/medicines/hiv/truvada/truvada_pi.pdf

truvada_pi.pdf The safety and effectiveness of TRUVADA for HIV-1 PrEP in at-risk adolescents weighing at least 35 kg is supported by data from adequate and well-controlled ...

8. descovyhcp.com descovyhcp.com/

DESCOVY (emtricitabine/tenofovir alafenamide) FOR PrEP ... DESCOVY for HIV-1 pre-exposure prophylaxis (PrEP) is indicated in at-risk adults and adolescents (≥35 kg) to reduce the risk of sexually acquired HIV-1 ...