An Overview of Tenofovir Alafenamide
January 19, 2017
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.
(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?
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?
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 2016.8 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?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.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?
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?
Tenofovir Alafenamide for HIV Treatment
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (DRV/COBI/FTC/TAF)
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
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)
For more details on the studies listed above, see the Health Professional Version.
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
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?
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?
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.
This article was provided by AIDSinfo. Visit the AIDSinfo website to find out more about their activities and publications.
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