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. Phase of Development:

The emtricitabine/tenofovir alafenamide fixed-dose combination (FDC) (brand name: Descovy) is in Phase III development for HIV prevention.

Five FDCs containing tenofovir alafenamide are U.S. Food and Drug Administration (FDA)-approved for HIV treatment: 1) elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (brand name: Genvoya), 2) emtricitabine/rilpivirine/tenofovir alafenamide (brand name: Odefsey), 3) Descovy, 4) bictegravir/emtricitabine/tenofovir alafenamide (brand name: Biktarvy), and 5) darunavir/cobicistat/emtricitabine/tenofovir alafenamide (brand name: Symtuza). As a stand-alone agent, tenofovir alafenamide (brand name: Vemlidy) is FDA-approved for chronic HBV infection treatment.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 ClinicalTrials.gov,3 and Full Prescribing Information for Genvoya, Odefsey, Descovy, Biktarvy, Symtuza, and Vemlidy4–9)

What is tenofovir alafenamide?

What is tenofovir alafenamide?

Tenofovir alafenamide is being studied as a stand-alone drug and as a component of fixed-dose combination (FDC) drugs to treat and prevent HIV infection.3,10 (Tenofovir alafenamide is a component of several FDA-approved FDC drugs to treat HIV. As a stand-alone drug, tenofovir alafenamide is FDA-approved to treat chronic hepatitis B virus infection [HBV]. The FDA-approved drugs are listed below.)

Tenofovir alafenamide belongs to a group of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).2 NRTIs block an HIV enzyme called reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.

Tenofovir alafenamide is a component of the following FDC drugs that are FDA-approved to treat HIV infection:

As a stand-alone drug, tenofovir alafenamide (brand name: Vemlidy) is FDA-approved to treat chronic HBV.9

Under the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), FDA has tentatively approved the FDC tablet dolutegravir/emtricitabine/tenofovir alafenamide for the treatment of HIV. This single-tablet regimen meets all FDA standards of approval for safety, efficacy, and quality, but it is only available for use in PEPFAR focus countries.11,12

To learn about how investigational drugs are tested during clinical trials, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

Which clinical trials are studying tenofovir alafenamide?

Which clinical trials are studying tenofovir alafenamide?

Tenofovir alafenamide for HIV treatment

Tenofovir alafenamide is being used in a Phase II trial (NCT03472326) evaluating an investigational drug called GS-9131. The study is evaluating GS-9131 for HIV treatment in women on a current HIV regimen that is not controlling the virus. In Part 2 of the trial, tenofovir alafenamide as a stand-alone drug is used in a GS-9131-containing HIV regimen.10

Tenofovir alafenamide for HIV prevention

Emtricitabine/Tenofovir Alafenamide (FTC/TAF; Descovy)

Study Names: DISCOVER; GS-US-412-2055; NCT02842086
Phase: Phase III
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Austria, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, United Kingdom
Purpose: The purpose of this study is to evaluate the safety and effectiveness of Descovy in preventing HIV infection in men and transgender women who have sex with men and are at high risk of acquiring HIV.3

Other HIV prevention studies involving tenofovir alafenamide-containing products include:

  • NCT03762772: A Phase I trial evaluating the safety and pharmacokinetics of a vaginal insert containing both tenofovir alafenamide and elvitegravir in women without HIV. This study is currently recruiting participants.13
  • NCT02985996: A Phase I trial evaluating the pharmacokinetics of Genvoya in different body compartments of men and transgender women, all of whom are HIV negative and have sex with men. This study is currently recruiting participants.14
  • NCT03499483: A Phase IV trial evaluating the use of Biktarvy in adults without HIV to prevent infection after a high-risk sexual contact. This study is not yet recruiting.15

For more details on the studies listed above, see the Health Professional version of this drug summary.

What side effects might tenofovir alafenamide cause?

What side effects might tenofovir alafenamide cause?

One goal of HIV research is to identify new drugs that have fewer side effects. In the DISCOVER study (NCT02842086) discussed under the previous question, the most common side effects were sexually transmitted diseases or exposures, diarrhea, common cold, and upper respiratory tract infections. Side effects were similar in participants taking either Descovy or Truvada. Descovy was shown to have a significantly improved bone and renal safety over Truvada.16

Information on other side effects related to use of tenofovir alafenamide as part of an FDC or as a stand-alone drug may be found in the following FDA drug labels: Genvoya, Odefsey, Descovy, Biktarvy, Symtuza, and Vemlidy.4–7,9

Because tenofovir alafenamide is still being studied, information on possible side effects of the drug is not complete. As testing of the drugs 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.

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: Tenofovir Alafenamide. https://chem.sis.nlm.nih.gov/chemidplus/rn/379270-37-8. Accessed March 22, 2019.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed March 22, 2019.
  3. 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. https://www.clinicaltrials.gov/ct2/show/NCT02842086. Accessed March 22, 2019.
  4. Gilead Sciences, Inc. Genvoya: full prescribing information, February 11, 2019. DailyMed. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34784acf-15ed-4715-b504-eb30430518e9. Accessed March 22, 2019.
  5. Gilead Sciences, Inc. Odefsey: full prescribing information, October 1, 2018. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ea3b9ec8-e04a-412c-8b3f-e5cbc7e641d5. Accessed March 22, 2019.
  6. Gilead Sciences, Inc. Descovy: full prescribing information, October 6, 2017. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06f66e98-e6ee-4538-9506-6c1282cc14c1. Accessed March 22, 2019.
  7. Gilead Sciences, Inc. Biktarvy: full prescribing information, September 17, 2018. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=664cb8f0-1f65-441b-b0d9-ba3d798be309. Accessed March 22, 2019.
  8. Janssen Products LP. Symtuza: full prescribing information, February 4, 2019. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=85a17d00-6b7c-41ea-a6b3-5ad924820dab. Accessed March 22, 2019.
  9. Gilead Sciences, Inc. Vemlidy: full prescribing information, February 11, 2019. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72e6b33c-0351-4070-9172-eeaa186c01d2. Accessed March 22, 2019.
  10. Gilead Sciences. A Phase 2 study to evaluate the efficacy of GS-9131 functional monotherapy in HIV-1-infected adults failing a nucleos(t)Ide reverse transcriptase inhibitor-containing regimen with nucleos(t)Ide reverse transcriptase inhibitor resistant virus, followed by continued treatment with a GS-9131+bictegravir+darunavir+ritonavir regimen. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 8, 2018. NLM Identifier: NCT03472326. https://clinicaltrials.gov/ct2/show/NCT03472326. Accessed March 22, 2019.
  11. Mylan: Press Release, dated February 20, 2018. Mylan receives tentative approval for combination HIV treatment DTG/FTC/TAF under FDA’s PEPFAR program. http://newsroom.mylan.com/2018-02-20-Mylan-Receives-Tentative-Approval-for-Combination-HIV-Treatment-DTG-FTC-TAF-Under-FDAs-PEPFAR-Program. Accessed March 22, 2019.
  12. U.S. Food and Drug Administration. President’s Emergency Plan for AIDS Relief (PEPFAR). https://www.fda.gov/InternationalPrograms/PEPFAR/default.htm. Published 2019. Accessed March 22, 2019.
  13. CONRAD. A Phase I study to assess safety, pharmacokinetics, and pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 16, 2018. NLM Identifier: NCT03762772. https://clinicaltrials.gov/ct2/show/NCT03762772. Accessed March 22, 2019.
  14. Emory University. Body compartment PK for new HIV pre-exposure prophylaxis modalities. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 5, 2016. NLM Identifier: NCT02985996. https://clinicaltrials.gov/ct2/show/NCT02985996. Accessed March 22, 2019.
  15. Fenway Community Health. A Phase IV open-label evaluation of safety, tolerability, and acceptability of a fixed-dose formulation of bictegravir, emtricitabine/tenofovir alafenamide (B/F/TAF) for non-occupational prophylaxis following potential exposure to HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 9, 2018. NLM Identifier: NCT03499483. https://clinicaltrials.gov/ct2/show/NCT03499483. Accessed March 22, 2019.
  16. Hare CB. The Phase 3 DISCOVER study: daily F/TAF or F/TDF for HIV preexposure prophylaxis. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. http://www.croiwebcasts.org/console/player/41210?mediaType=slideVideo&&crd_fl=1&ssmsrq=1553222202879&ctms=5000&csmsrq=856. Accessed March 22, 2019.

Last Reviewed: March 22, 2019