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: Five fixed-dose combination (FDC) tablets 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) emtricitabine/tenofovir alafenamide (brand name: Descovy), 4) bictegravir/emtricitabine/tenofovir alafenamide (brand name: Biktarvy), and 5) darunavir/cobicistat/emtricitabine/tenofovir alafenamide (brand name: Symtuza).

Descovy is also FDA-approved for use in certain at-risk individuals as an agent for HIV pre-exposure prophylaxis (PrEP).

As a stand-alone agent, tenofovir alafenamide (brand name: Vemlidy) is FDA-approved for chronic HBV infection treatment. It does not appear that stand-alone tenofovir alafenamide will be developed for HIV treatment, although there are two trials that are utilizing stand-alone tenofovir alafenamide to form antiretroviral regimens for treating HIV.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 Full Prescribing Information for Genvoya, Odefsey, Descovy, Biktarvy, Symtuza, and Vemlidy,3-8 and ClinicalTrials.gov9,10)

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.9,11 (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.8

Under the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), FDA has tentatively approved the FDC tablet dolutegravir/emtricitabine/tenofovir alafenamide and the FDC tablet dolutegravir/lamivudine/tenofovir alafenamide for the treatment of HIV. These single-tablet regimens meet all FDA standards of approval for safety, efficacy, and quality, but are only available for use in PEPFAR focus countries.12,13

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 2 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.9

The stand-alone version of tenofovir alafenamide will also be used in a Phase 2 trial (NCT04143594) evaluating the efficacy of GS-6207, an investigational drug, in combination with other antiretrovirals for the treatment of HIV.10

Tenofovir Alafenamide for HIV Prevention

Descovy is FDA-approved for use in certain adults and adolescents as HIV PrEP to reduce the risk of HIV-1 infection from sexual acquisition. This approved use excludes individuals at risk of HIV infection from receptive vaginal sex.5

There are several early-phase HIV prevention studies involving tenofovir alafenamide-containing products that are ongoing or planned, including:
  • MTN-039 (NCT04047420): A Phase 1 safety and pharmacokinetic trial evaluating the rectal administration of a tenofovir alafenamide/elvitegravir insert in individuals without HIV. See the ClinicalTrials.gov record for this study’s status.15
  • NCT03976752: A Phase 1 pharmacokinetic study to evaluate Genvoya as a potential regimen to prevent HIV infection soon after potential exposure. Participants are men who have sex with men and who do not have HIV. This study is currently recruiting participants.16
  • NCT03472963: A Phase 1 pharmacokinetic study to evaluate Genvoya and darunavir as potential regimens to prevent HIV infection soon after potential exposure. Participants are men who have sex with men and who do not have HIV. This study is currently recruiting participants.17
  • NCT03499483: A Phase 4 trial evaluating the use of Biktarvy in adults without HIV to prevent infection after a high-risk sexual contact. This study is currently recruiting participants.18

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?

Information on 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.3-8

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 more 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 December 4, 2019
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed December 4, 2019
  3. 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 December 4, 2019
  4. 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 December 4, 2019
  5. Gilead Sciences, Inc. Descovy: full prescribing information, October 11, 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06f66e98-e6ee-4538-9506-6c1282cc14c1. Accessed December 4, 2019
  6. Gilead Sciences, Inc. Biktarvy: full prescribing information, August 8, 2019. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=664cb8f0-1f65-441b-b0d9-ba3d798be309. Accessed December 4, 2019
  7. Janssen Products LP. Symtuza: full prescribing information, June 6, 2019. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=85a17d00-6b7c-41ea-a6b3-5ad924820dab. Accessed December 4, 2019
  8. 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 December 4, 2019
  9. 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 December 4, 2019
  10. Gilead Sciences. A Phase 2 randomized, open label, active controlled study evaluating the safety and efficacy of long-acting capsid inhibitor GS-6207 in combination with other antiretroviral agents in people living with HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 28, 2019. NLM Identifier: NCT04143594. https://clinicaltrials.gov/ct2/show/NCT04143594. Accessed December 4, 2019
  11. 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 December 4, 2019
  12. 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 December 4, 2019
  13. U.S. Food and Drug Administration (FDA). Tentatively approved and approved antiretrovirals eligible for procurement under the President’s Emergency Plan for AIDS Relief. http://www.fda.gov/international-programs/presidents-emergency-plan-aids-relief-pepfar/tentatively-approved-and-approved-antiretrovirals-eligible-procurement-under-presidents-emergency. Accessed December 4, 2019
  14. 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 December 4, 2019
  15. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 1 open label safety and pharmacokinetic study of rectal administration of a tenofovir alafenamide/elvitegravir insert at two dose levels. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 5, 2019. NLM Identifier: NCT04047420. https://clinicaltrials.gov/ct2/show/NCT04047420. Accessed December 4, 2019
  16. Emory University. Body compartment pharmacokinetics of anti-retroviral agents that may be considered for future on-demand peri-exposure HIV prophylaxis regimens. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 4, 2019. NLM Identifier: NCT03976752. https://clinicaltrials.gov/ct2/show/NCT03976752. Accessed December 4, 2019
  17. Emory University. Body compartment pharmacokinetics of anti-retroviral agents that may be used for future HIV post-exposure prophylaxis regimens. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 15, 2018. NLM Identifier: NCT03472963. https://clinicaltrials.gov/ct2/show/NCT03472963. Accessed December 4, 2019
  18. 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 December 4, 2019

Last Reviewed: December 4, 2019

Print