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Drugs

Tenofovir Alafenamide

Tenofovir Alafenamide

Other Names: GS-7340, TAF, TFV alafenamide, prodrug of tenofovir, tenofovir alafenamide fumarate Drug Class: Nucleoside Reverse Transcriptase Inhibitors Molecular Formula: C21 H29 N6 O5 P Registry Number: 379270-37-8 (CAS) Chemical Name: isopropyl (2S)-2-[[[(1R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate Chemical Class: Purine Nucleotides Organization: Gilead Sciences, Inc. (The darunavir/cobicistat/emtricitabine/tenofovir alafenamide fixed-dose combination [FDC] is being developed by Janssen R&D Ireland.) Phase of Development:

Two tenofovir alafenamide-containing FDC regimens are in Phase III development for HIV treatment: darunavir/cobicistat/emtricitabine/tenofovir alafenamide and bictegravir/emtricitabine/tenofovir alafenamide. The emtricitabine/tenofovir alafenamide FDC tablet (brand name: Descovy) is in Phase III development for HIV prevention.

The following 3 tenofovir alafenamide-containing FDC tablets are FDA-approved for HIV treatment: 1) elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (brand name: Genvoya), 2) emtricitabine/rilpivirine/tenofovir alafenamide (brand name: Odefsey), and 3) Descovy. As a stand-alone agent, tenofovir alafenamide (brand name: Vemlidy) is FDA-approved for chronic hepatitis B virus (HBV) infection treatment.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 ClinicalTrials.gov,3-5 and Gilead Sciences, Inc. press releases6-10)

What is an investigational drug?

What is an investigational drug?

An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.

To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.

What is tenofovir alafenamide?

What is tenofovir alafenamide?

Tenofovir alafenamide is an investigational drug that is being studied for the treatment of HIV infection. It is also being studied for the treatment of chronic hepatitis B virus (HBV) infection.11,12

Tenofovir alafenamide belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).2 NRTIs block an HIV enzyme called reverse transcriptase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.

Tenofovir alafenamide is currently being studied as a component of 2 different investigational fixed-dose combination (FDC) drugs for the treatment of HIV infection. (FDC drugs include 2 or more drugs in a single dosage form, such as a capsule or tablet.) Tenofovir alafenamide is being studied in the following combinations:    

Three FDC tablets are FDA-approved. The first FDC tablet contains elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (brand name: Genvoya) and was approved in November 2015.6 The second FDC tablet contains emtricitabine/rilpivirine/tenofovir alafenamide (brand name: Odefsey) and was approved in March 2016.The third FDC tablet contains emtricitabine/tenofovir alafenamide (brand name: Descovy) and was approved in April 2016. Descovy is also being studied in Phase III studies for HIV prevention.5,9

How are clinical trials of investigational drugs conducted?

How are clinical trials of investigational drugs conducted?

Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.13

  • Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
  • Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
  • Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.13

In most cases, an investigational drug must be proven effective and must show continued safety in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.13 (Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different sub-levels typically mean that a study is researching certain types of information or using a certain type of participant population.)

In what phase of testing is tenofovir alafenamide?

In what phase of testing is tenofovir alafenamide?

Tenofovir alafenamide, as part of the following 2 FDC tablets, is currently being studied in Phase III clinical trials for HIV treatment:

Tenofovir alafenamide, as part of the Descovy FDC tablet, is currently being studied in Phase III clinical trials for HIV prevention.5

What are some studies on tenofovir alafenamide?

What are some studies on tenofovir alafenamide?

Tenofovir Alafenamide for HIV Treatment

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (DRV/COBI/FTC/TAF)
Study Names: GS-US-299-0102; NCT01565850
Sponsor: Gilead Sciences
Phase: II
Location: United States and Puerto Rico 
Participants:

  • Participants were HIV-infected adults who had never received HIV medicines before the start of the study.
  • Participants had viral load levels of at least 5,000 copies/mL. (Viral load is the amount of HIV in a blood sample.)
  • Participants had CD4 counts greater than 50 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)
  • At the start of the study, participants had HIV that could be treated with the HIV drugs darunavir, emtricitabine, and tenofovir disoproxil fumarate.

Purpose: The purpose of this study was to look at the safety and effectiveness of the darunavir/cobicistat/emtricitabine/tenofovir alafenamide FDC tablet over 48 weeks and to compare the FDC tablet to cobicistat-boosted darunavir + emtricitabine/tenofovir disoproxil fumarate (Truvada). (Boosting means using an HIV medicine or other drug to increase the effectiveness of another HIV medicine. In this case, cobicistat is used to increase the effectiveness of darunavir.)14,15

Two Phase III studies are currently evaluating the darunavir/cobicistat/emtricitabine/tenofovir alafenamide FDC tablet. One of the studies (NCT02431247) involves participants who had never received HIV medicines before the start of the study. The other study (NCT02269917) involves participants who had received HIV medicines before and who had viral loads suppressed to less than 50 copies/mL. Both studies are ongoing, but not currently recruiting participants.3,16

Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

Several Phase III studies are looking at an FDC tablet containing bictegravir/emtricitabine/tenofovir alafenamide. (Bictegravir, also known as GS-9883, is an investigational integrase inhibitor, which blocks an enzyme called integrase to prevent HIV from multiplying.) Two of the studies (NCT02607956 and NCT02607930) involve participants who had never taken HIV medicines before or had taken HIV treatment medicines for 10 days or less before the study. Two other studies (NCT02603107 and NCT02603120) involve participants who had received HIV medicines before starting the study and who had viral loads suppressed to less than 50 copies/mL. All 4 studies are ongoing but not currently recruiting participants. A Phase II/III study (NCT02881320), which is currently recruiting participants, will look at the FDC tablet in children and adolescents whose viral loads are suppressed to less than 50 copies/mL.4,17-21

 Tenofovir Alafenamide for HIV Prevention

Emtricitabine/Tenofovir Alafenamide (FTC/TAF; Descovy)
A Phase III study (NCT02842086) will evaluate Descovy’s safety and effectiveness in preventing HIV infection in men who have sex with men and in transgender women who are at risk of acquiring HIV. This study is currently recruiting participants.5

For more details on the studies listed above, see the Health Professional Version.

What side effects might tenofovir alafenamide cause?

What side effects might tenofovir alafenamide cause?

In the Phase II study (NCT01565850) of a darunavir/cobicistat/emtricitabine/tenofovir alafenamide FDC tablet discussed under the previous question, most side effects were mild to moderate in severity. Some side effects that were reported by participants receiving the darunavir/cobicistat/emtricitabine/tenofovir alafenamide tablet included diarrhea, upper respiratory tract infection, fatigue, nausea, and rash.14,15,22

Other side effect information on tenofovir alafenamide might be found in the following FDA drug labels: Genvoya, Odefsey, Descovy, and Vemlidy.23-26

Because tenofovir alafenamide is still being studied, information on possible side effects of the drug is not complete. As testing of tenofovir alafenamide continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying tenofovir alafenamide?

Where can I get more information about clinical trials studying tenofovir alafenamide?

More information about tenofovir alafenamide-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

How can I find more information about participating in a clinical trial?

How can I find more information about participating in a clinical trial?

Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.13

Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/379270-37-8. Last accessed on January 19, 2017.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on January 19, 2017.
  3. Janssen Sciences Ireland UC. A Phase 3, Randomized, Active-controlled, Double-blind Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Once Daily Fixed Dose Combination Regimen Versus a Regimen Consisting of Darunavir/Cobicistat Fixed Dose Combination Coadministered With Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 27, 2015. NLM Identifier: NCT02431247. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02431247. Last accessed on January 19, 2017.
  4. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, Antiretroviral Treatment-Naïve Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02607930. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02607930. Last accessed on January 19, 2017.
  5. 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. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 20, 2016. NLM Identifier: NCT02842086. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02842086. Last accessed on January 19, 2017.
  6. Gilead: Press Release, dated November 5, 2015. U.S. Food and Drug Administration Approves Gilead’s Single Tablet Regimen Genvoya® (Elvitegravir, Cobicistat, Emtricitabine and Tenofovir Alafenamide) for Treatment of HIV-1 Infection. Available at: http://www.gilead.com/news/press-releases/2015/11/us-food-and-drug-administration-approves-gileads-single-tablet-regimen-genvoya-elvitegravir-cobicistat-emtricitabine-and-tenofovir-alafenamide-for-treatment-of-hiv1-infection. Last accessed on January 19, 2017.
  7. Gilead: Press Release, dated December 29, 2014. Gilead Announces Amended Agreements With Janssen to Develop and Commercialize Tenofovir Alafenamide-Based Single Tablet Regimens for HIV Treatment. Available at: http://www.gilead.com/news/press-releases/2014/12/gilead-announces-amended-agreements-with-janssen-to-develop-and-commercialize-tenofovir-alafenamidebased-single-tablet-regimens-for-hiv-treatment. Last accessed on January 19, 2017.
  8. Gilead: Press Release, dated March 1, 2016. U.S. Food and Drug Administration Approves Gilead’s Second TAF-Based Single Tablet Regimen Odefsey® (Emtricitabine, Rilpivirine, Tenofovir Alafenamide) for the Treatment of HIV-1 Infection. Available at: http://www.gilead.com/news/press-releases/2016/3/us-food-and-drug-administration-approves-gileads-second-tafbased-single-tablet-regimen-odefsey-emtricitabine-rilpivirine-tenofovir-alafenamide-for-the-treatment-of-hiv1-infection. Last accessed on January 19, 2017.
  9. Gilead: Press Release, dated April 4, 2016. U.S. Food and Drug Administration Approves Descovy® (Emtricitabine, Tenofovir Alafenamide), Gilead’s Third TAF-Based HIV Therapy. Available at: http://www.gilead.com/news/press-releases/2016/4/us-food-and-drug-administration-approves-descovy-emtricitabine-tenofovir-alafenamide-gileads-third-tafbased-hiv-therapy. Last accessed on January 19, 2017.
  10. Gilead: Press Release, dated November 10, 2016. U.S. Food and Drug Administration Approves Gilead’s Vemlidy® (Tenofovir Alafenamide) for the Treatment of Chronic Hepatitis B Virus Infection. Available at: http://www.gilead.com/news/press-releases/2016/11/us-food-and-drug-administration-approves-gileads-vemlidy-tenofovir-alafenamide-for-the-treatment-of-chronic-hepatitis-b-virus-infection. Last accessed on January 19, 2017.
  11. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg Positive, Chronic Hepatitis B. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 20, 2013. NLM Identifier: NCT01940471. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01940471. Last accessed on January 19, 2017.
  12. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Negative, Chronic Hepatitis B. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 20, 2013. NLM Identifier: NCT01940341. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01940341. Last accessed on January 19, 2017.
  13. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on January 19, 2017.
  14. Gilead Sciences. A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Darunavir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Cobicistat-boosted Darunavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in HIV-1 Infected, Antiretroviral Treatment Naive Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 27, 2012. NLM Identifier: NCT01565850. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01565850. Last accessed on January 19, 2017.
  15. Mills A, Ortiz R, Crofoot G Jr, et al. 48 Week Study of the First PI-based Single Tablet-Regimen (STR) Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) vs. Darunavir (DRV) boosted by Cobicistat (COBI) and Emtricitabine/Tenofovir Disoproxil Fumarate (TVD) in HIV-Infected Treatment-Naïve Adults. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 5-9, 2014; Washington, DC. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2014. Available at: http://www.natap.org/2014/ICAAC/ICAAC_07.htm. Last accessed on January 19, 2017.
  16. Janssen R&D Ireland. A Phase 3, Randomized, Active-controlled, Open-label Study to Evaluate the Efficacy, Safety and Tolerability of Switching to a Darunavir/ Cobicistat/ Emtricitabine/ Tenofovir Alafenamide (D/C/F/TAF) Once-daily Single-tablet Regimen Versus Continuing the Current Regimen Consisting of a Boosted Protease Inhibitor (bPI) Combined With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) in Virologically-suppressed, Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 17, 2014. NLM Identifier: NCT02269917. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02269917. Last accessed on January 19, 2017.
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  19. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Switching From a Regimen of Dolutegravir and ABC/3TC, or a Fixed Dose Combination (FDC) of ABC/DTG/3TC to a FDC of GS-9883/F/TAF in HIV-1 Infected Subjects Who Are Virologically Suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02603120. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02603120. Last accessed on January 19, 2017.
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  22. Mills A, Ortiz R, Crofoot G Jr, et al. 48 Week Study of the First PI-based Single Tablet-Regimen (STR) Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) vs. Cobicistat (COBI)-boosted Darunavir (DRV) and Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) in Treatment-naïve (TN) Adults. Abstract presented at: 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 5-9, 2014; Washington, DC. Abstract H-647c. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=19dd97cd-1a73-4adc-9cdb-36743946ec6b&cKey=d7994d1a-681e-49f4-ba2f-c2a15513b895&mKey=%7b5D6B1802-E453-486B-BCBB-B11D1182D8BB%7d. Last accessed on January 19, 2017.
  23. Gilead Sciences, Inc. Genvoya - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide fumarate tablet: Full Prescribing Information, September 16, 2016. DailyMed. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34784acf-15ed-4715-b504-eb30430518e9. Last accessed on January 19, 2017.
  24. Gilead Sciences, Inc. ODEFSEY- emtricitabine, rilpivirine hydrochloride and tenofovir alafenamide fumarate tablet: Full Prescribing Information, March 4, 2016. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ea3b9ec8-e04a-412c-8b3f-e5cbc7e641d5. Last accessed on January 19, 2017.
  25. Gilead Sciences, Inc. DESCOVY - emtricitabine and tenofovir alafenamide fumarate tablet: Full Prescribing Information, April 8, 2016. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06f66e98-e6ee-4538-9506-6c1282cc14c1. Last accessed on January 19, 2017.
  26. Gilead Sciences, Inc. VEMLIDY- tenofovir alafenamide fumarate tablet: Full Prescribing Information, November 16, 2016. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72e6b33c-0351-4070-9172-eeaa186c01d2. Last accessed on January 19, 2017.
 

Last Reviewed: January 19, 2017