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AIDSinfo Drug Database

AIDSinfo Drug Database

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Tenofovir Alafenamide  Audio icon

Other Names: GS-7340, prodrug of tenofovir, TAF, 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
Company: Gilead Sciences, Inc.
Phase of Development: Phase II and III (as part of fixed-dose combination [FDC] tablets; one FDC tablet is in Phase II testing, and another one is in Phase III testing)
Chemical Image:
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tenofovir alafenamide
tenofovir alafenamide
Molecular Weight: 476.4711
(Compound details obtained from ChemIDplus Advanced1, NIAID Therapeutics Database2, and ClinicalTrials.gov3)

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.

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 in people who are not infected with HIV.4

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 a prodrug, which means that it is an inactive drug. Once taken, a prodrug does not work until the body converts it into an active form. In the body, tenofovir alafenamide is converted to tenofovir diphosphate (TFV-DP).5

Studies suggest that tenofovir alafenamide may be more effective against HIV and cause fewer side effects than the FDA-approved NRTI tenofovir disoproxil fumarate (brand name: Viread).6 

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

o elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide7 
o darunavir/cobicistat/emtricitabine/tenofovir alafenamide3 

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.8

  • 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.8

In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by the FDA for sale in the United States. Some drugs go through the FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by the 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.8

In what phase of testing is tenofovir alafenamide?

Tenofovir alafenamide, as part of two different fixed-dose combination tablets, is currently being studied in Phase II and Phase III clinical trials.2,3 

What have recent studies shown about tenofovir alafenamide?

In a 10-day, early-phase study, three different doses of tenofovir alafenamide taken once daily were compared to placebo and to tenofovir disoproxil fumarate (given at the standard dose) in HIV-infected participants. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) Some participants had never taken HIV medicines before entering the study (treatment-naive), and others had taken HIV medicines previously (treatment-experienced). Study participants did not receive additional HIV medicines as part of a background regimen. (A background regimen is a combination of drugs that are not being studied as the investigational drug[s] in the clinical trial, but are being given to help control a participant’s HIV infection.)6,9 

In this study, tenofovir alafenamide at the two higher doses studied (25 mg and 40 mg) proved more effective than tenofovir disoproxil fumarate at lowering viral load (the amount of HIV in the blood). Tenofovir alafenamide also resulted in higher TFV-DP levels inside cells and lower tenofovir concentrations in the blood than tenofovir disoproxil fumarate did. In terms of safety, there were no reports of significant laboratory abnormalities or serious side effects related to tenofovir alafenamide use.6

Additional Phase II and III trials involving tenofovir alafenamide as part of fixed-dose combination tablets are under way in treatment-naive adults.3,7

What side effects might tenofovir alafenamide cause?

In the 10-day, early-phase study discussed under the previous question, no serious side effects occurred.6

In a Phase II study of a fixed-dose combination tablet containing tenofovir alafenamide, the following side effects were reported after 24 weeks of treatment: nausea, diarrhea, fatigue, headache, and infection of the upper airway (such as the common cold).10

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 study summaries. Click on the title of any trial in the list to see the trial summary and more information about the study.

I am interested in participating in a clinical trial of tenofovir alafenamide. 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.8

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.


1. United States National Library of Medicine. ChemIDplus Advanced.

2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development.

3. 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: Bethesda (MD): National Library of Medicine (US). Registered on March 27, 2012. NLM Identifier: NCT01565850. Last accessed April 12, 2013.

4. Gilead Sciences. A Phase 1b Randomized, Open Label, Active-Controlled Study to Assess the Safety, Viral Kinetics, and Anti-HBV Activity of GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B (CHB) Infection. In: Bethesda (MD): National Library of Medicine (US). Registered on August 21, 2012. NLM Identifier: NCT01671787. Last accessed April 12, 2013.

5. García-Lerma JG, Aung W, Cong ME, et al. Natural substrate concentrations can modulate the prophylactic efficacy of nucleotide HIV reverse transcriptase inhibitors. J Virol. 2011 Jul;85(13):6610-7.

6. Ruane P, DeJesus E, Berger D, et al. GS-7340 25 mg and 40 mg Demonstrate Superior Efficacy to Tenofovir 300 mg in a 10-day Monotherapy Study of HIV-1+ Patients. Paper presented at: 19th Conference on Retroviruses and Opportunistic Infections (CROI); March 5-8, 2012; Seattle, WA. Paper 103. 

7. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate in HIV-1 Positive, Antiretroviral Treatment-Naïve Adults. In: Bethesda (MD): National Library of Medicine (US). Registered on January 16, 2013. NLM Identifier: NCT01780506. Last accessed April 12, 2013.

8. National Institutes of Health (NIH). NIH Clinical Research Trials and You.

9. Mascolini M. Low-Dose, Cell-Homing Tenofovir Prodrug Outdoes TDF in 10-Day Study. Conference Reports for National AIDS Treatment Advocacy Project (NATAP): 19th Conference on Retroviruses and Opportunistic Infections (CROI); March 5-8, 2012;  Seattle, WA. Accessed April 22, 2013.

10. Zolopa A, Ortiz R, Sax P, et al. Comparative Study of Tenofovir Alafenamide vs Tenofovir Disoproxil Fumarate, Each with Elvitegravir, Cobicistat, and Emtricitabine, for HIV Treatment. Paper presented at: 20th Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2013; Atlanta, GA. Paper 99LB.

Last Reviewed: May 29, 2013

Last Updated: May 29, 2013

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