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Tenofovir Alafenamide  Audio icon

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
Company: 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 studies: darunavir/cobicistat/emtricitabine/tenofovir alafenamide and GS-9883/emtricitabine/tenofovir alafenamide.

The following three tenofovir alafenamide-containing FDC tablets are FDA-approved: 1) elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (brand name: Genvoya) was approved in November 2015, 2) emtricitabine/rilpivirine/tenofovir alafenamide (brand name: Odefsey) was approved in March 2016, and 3) emtricitabine/tenofovir alafenamide (brand name: Descovy) was approved in April 2016.

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Chemical Image:
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tenofovir alafenamide
tenofovir alafenamide
Molecular Weight: 476.4711
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 ClinicalTrials.gov,3,4 and Gilead Sciences, Inc. press releases5-8)
Patent Version Content

Pharmacology


Mechanism of Action: Nucleotide reverse transcriptase inhibitor. Tenofovir alafenamide is a phosphonoamidate prodrug of the nucleotide analog tenofovir (TFV). Tenofovir alafenamide was designed to circulate systemically as the prodrug and undergo conversion to tenofovir intracellularly, achieving higher active metabolite concentrations in peripheral blood mononuclear cells and lower plasma tenofovir exposures than tenofovir disoproxil fumarate (tenofovir DF; TDF) does.9-11

Tenofovir alafenamide is predominantly metabolized intracellularly to tenofovir. This intracellular metabolism is primarily catalyzed by cathepsin A (CatA). Inside cells, tenofovir alafenamide is initially hydrolyzed to a partially stable metabolite, from which the phenol group is spontaneously released, forming a cell-impermeable tenofovir-alanine (TFV-Ala) intermediate. Tenofovir-alanine is converted to parent tenofovir, which undergoes subsequent phosphorylations to yield the active tenofovir diphosphate (TFV-DP) metabolite.12-14 Tenofovir diphosphate inhibits the activity of HIV reverse transcriptase by competing with natural substrates and causing DNA chain termination after being incorporated into viral DNA.15

Tenofovir alafenamide has also demonstrated in vitro and in vivo activity against HBV.16,17

Half-life (T½): The median terminal half-life of tenofovir alafenamide is 0.51 hours. The active metabolite, tenofovir diphosphate, has an intracellular half-life of 150 to 180 hours.18

Metabolism/Elimination: CYP3A-mediated metabolism of tenofovir alafenamide is minor.19 Following single-dose administration of radiolabeled tenofovir alafenamide 25 mg in healthy male participants, tenofovir alafenamide was extensively metabolized, with 47% of the administered dose recovered in feces and 36% recovered in urine, predominately as the metabolite tenofovir. Minimal amounts of unchanged tenofovir alafenamide were excreted in urine. Uric acid was the predominant species in plasma over time, but did not change total plasma uric acid concentrations.20

Resistance: In vitro, HIV-1 isolates with reduced susceptibility to tenofovir alafenamide have been selected, including virus with the K65R substitution (sometimes with S68N or L429I substitutions) and virus with the K70E substitution.18

The K65R and K70E tenofovir resistance substitutions can result in reduced susceptibility to abacavir, didanosine, emtricitabine, lamivudine, and tenofovir. HIV-1 containing multiple thymidine analog mutations (TAMs; M41L, D67N, K70R, L210W, T215F/Y, K219Q/E/N/R) showed resistance to tenofovir alafenamide in cell culture. In addition, multi-nucleoside resistant virus with a T69S double insertion mutation or with a Q151M mutation complex including K65R exhibited in vitro resistance to tenofovir alafenamide.18

In a Phase II study (GS-US-299-0102) comparing the FDC tablet darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/COBI/FTC/TAF) versus cobicistat-boosted darunavir plus emtricitabine/tenofovir DF (DRV + COBI + FTC/TDF) in treatment-naive adults, six participants (5.8%) receiving DRV/COBI/FTC/TAF and two participants (4%) receiving DRV + COBI + FTC/TDF met criteria for resistance analysis because of virologic rebound through 48 weeks. However, no mutations associated with tenofovir DF, emtricitabine, or darunavir were detected in these participants.21,22

Additional information on resistance mutations associated with tenofovir alafenamide use may be described in the Genvoya, Odefsey, and Descovy full prescribing labels.18,23,24


Clinical Trials


Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (DRV/COBI/FTC/TAF)
Study Identifiers: GS-US-299-0102; NCT01565850
Phase: II
Study Purpose: 48-week safety and efficacy study comparing the single-tablet FDC regimen DRV/COBI/FTC/TAF versus DRV + COBI + FTC/TDF
Study Population: HIV-infected, treatment-naive adults
Dosing: Treatments were administered orally and once daily. Participants were assigned to one of the following two groups:

  • DRV/COBI/FTC/TAF (800/150/200/10 mg) single-tablet regimen, plus placebos to match DRV + COBI + FTC/TDF
  • darunavir 800 mg (given as two 400-mg tablets) + cobicistat 150 mg + emtricitabine/tenofovir DF (200/300 mg) (Truvada), plus placebo to match DRV/COBI/FTC/TAF.21,22,25

Selected Study Results:

Phase III studies evaluating DRV/COBI/FTC/TAF are ongoing. One of the Phase III studies (NCT02431247) is evaluating DRC/COBI/FTC/TAF versus DRV/COBI + FTC/TDF in treatment-naive adults. The other Phase III study (NCT02269917) is evaluating switching from a regimen of a boosted PI + FTC/TDF to DRV/COBI/FTC/TAF versus continuing on a boosted PI + FTC/TDF in virologically suppressed adults.4,26


GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/FTC/TAF)
Four Phase III studies will be evaluating an FDC tablet containing GS-9883/FTC/TAF (50/200/25 mg). GS-9883 is an investigational INSTI that does not require boosting.4,27-30

Two of the Phase III studies will evaluate GS-9883/FTC/TAF in treatment-naive adults, with one study (GS-US-380-1490) comparing GS-9883/FTC/TAF versus dolutegravir (DTG) + FTC/TAF and the other study (GS-US-380-1489) comparing GS-9883/FTC/TAF versus abacavir/dolutegravir/lamivudine (ABC/DTG/3TC).4,28

The other Phase III studies (GS-US-380-1878 and GS-US-380-1844) include virologically suppressed adults and are evaluating the safety and efficacy of switching to a GS-9883/FTC/TAF FDC regimen from either 1) a regimen containing boosted atazanavir (ATV) or boosted DRV + either FTC/TDF or ABC/3TC or 2) a regimen consisting of ABC, DTG, and 3TC.29,30

 

Tenofovir Alafenamide (stand-alone agent)
As a stand-alone agent, tenofovir alafenamide is currently being studied in Phase III trials for the treatment of chronic HBV infection.31,32


Adverse Events


In Study GS-US-299-0102, most adverse events were mild to moderate in severity. Adverse events occurring in at least 10% of participants in the DRV/COBI/FTC/TAF group included diarrhea, upper respiratory tract infection, fatigue, nausea, and rash. Two participants in each arm experienced an adverse event leading to study discontinuation: rash and substance dependence in the DRV/COBI/FTC/TAF arm and worsening diarrhea and proximal renal tubulopathy in the DRV + COBI + FTC/TDF arm. Participants in the DRV/COBI/FTC/TAF arm had significantly less increase in proximal tubular proteinuria and less reduction in estimated glomerular filtration rate (eGFR) when compared to participants in the DRV + COBI + FTC/TDF arm. Change in spine and hip bone mineral density (BMD) was significantly less with DRV/COBI/FTC/TAF than DRV + COBI + FTC/TDF. No fractures were reported in either group.21,25

Other adverse events associated with tenofovir alafenamide may be described in the Genvoya, Odefsey, and Descovy full prescribing labels.18,23,24


Drug Interactions


Tenofovir alafenamide does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or UGT1A1. Tenofovir alafenamide is a weak inhibitor of CYP3A in vitro. Tenofovir alafenamide is a substrate of P-gp, BCRP, OATP1B1, and OATP1B3 and a weak inhibitor of both OCT1 and MATE1. Drugs that inhibit P-gp and/or BCRP may increase the absorption of tenofovir alafenamide, while drugs that induce P-gp activity may decrease the absorption of tenofovir alafenamide. Tenofovir alafenamide does not interact with renal transporters OAT1 or OAT3.17,33,34

There were no clinically relevant drug interactions found between efavirenz and a co-formulated FDC of emtricitabine/tenofovir alafenamide in healthy participants. Dose adjustments are not required when efavirenz is co-administered with emtricitabine/tenofovir alafenamide FDC or with tenofovir alafenamide as a stand-alone agent.19

Because of inhibition of CatA-mediated activation of tenofovir alafenamide in vitro, tenofovir alafenamide co-administration with the covalent hepatitis C virus (HCV) protease inhibitors telaprevir and boceprevir may be contraindicated. However, in vitro studies have shown that darunavir and other HIV and HCV protease inhibitors demonstrate no pharmacological antagonism with tenofovir alafenamide.RPV/FTC/TAF or EVG/COBI/FTC/TAF can be co-administered with the anti-HCV fixed-dose combination drug ledipasvir/sofusbuvir without dose modifications.35

The drug-drug interaction potential of tenofovir alafenamide with rilpivirine, ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), ritonavir-boosted lopinavir (LPV/r), and dolutegravir were investigated in two studies in healthy participants. Tenofovir alafenamide 25 mg co-administered with rilpivirine 25 mg had no effect on the pharmacokinetic (PK) parameters of rilpivirine and had no relevant effect on tenofovir alafenamide exposures. Co-administration of tenofovir alafenamide 10 mg plus emtricitabine 200 mg had no effect on the PK of ATV/r, DRV/r, LPV/r or dolutegravir; no relevant effect on tenofovir alafenamide exposures occurred with either DRV/r or DTG. However, ATV/r and LPV/r increased tenofovir alafenamide and tenofovir exposures. These results informed investigators on tenofovir alafenamide doses to be used in the development of the FDC FTC/TAF, in combination with other agents.33,36

Other drug interactions associated with tenofovir alafenamide may be described in the Genvoya, Odefsey, and Descovy full prescribing labels.18,23,24


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 April 22, 2016.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on April 22, 2016.
  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 April 22, 2016.
  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 April 22, 2016.
  5. 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 April 22, 2016.
  6. 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 April 22, 2016.
  7. 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 April 22, 2016.
  8. 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 April 22, 2016.
  9. Birkus G, Bam RA, Frey CR, et al. Intracellular Activation Pathways for GS-7340 and the Effect of Antiviral Protease Inhibitors. Poster presented at: 19th Conference on Retroviruses and Opportunistic Infections (CROI); March 5-8, 2012; Seattle, WA. Poster 577. Available at: http://www.retroconference.org/2012b/PDFs/577.pdf. Last accessed on May 23, 2013.
  10. Lee WA, He GX, Eisenberg E, et al. Selective Intracellular Activation of a Novel Prodrug of the Human Immunodeficiency Virus Reverse Transcriptase Inhibitor Tenofovir Leads to Preferential Distribution and Accumulation in Lymphatic Tissue. Antimicrob Agents Chemother. 2005 May;49(5):1898-906. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087627/. Last accessed on April 22, 2016.
  11. Ruane PJ, DeJesus E, Berger D, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):449-55. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23807155. Last accessed on April 22, 2016.
  12. Birkus G, Kutty N, He GX, et al. Activation of 9-[(R)-2-[[(S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino] phenoxyphosphinyl]-methoxy]propyl]adenine (GS-7340) and Other Tenofovir Phosphonoamidate Prodrugs by Human Proteases. Mol Pharmacol. 2008 Jul;74(1):92-100. Available at: http://molpharm.aspetjournals.org/content/74/1/92.long. Last accessed on April 22, 2016.
  13. Herman BD and Sluis-Cremer N. Molecular Pharmacology of Nucleoside and Nucleotide HIV-1 Reverse Transcriptase Inhibitors. In: Gallelli L, ed. Pharmacology. InTech, DOI: 10.5772/32969; 2012: p 63-81. Available at: http://cdn.intechopen.com/pdfs-wm/32120.pdf. Last accessed on April 22, 2016.
  14. Sax PE, Zolopa A, Brar I, et al. Tenofovir Alafenamide Vs. Tenofovir Disoproxil Fumarate in Single Tablet Regimens for Initial HIV-1 Therapy: A Randomized Phase 2 Study. J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):52-8. Available from National AIDS Treatment Advocacy Project (NATAP) at: http://www.natap.org/2014/HIV/Tenofovir_Alafenamide_Vs__Tenofovir_Disoproxil.9.pdf. Last accessed on April 22, 2016.
  15. 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126530/. Last accessed on April 22, 2016.
  16. Lee W, He G, Mulato A, et al. In vivo and in vitro characterization of GS 7340, an isopropylalaninyl phenyl ester prodrug of tenofovir: selective intracellular activation of GS 7340 leads to preferential distribution in lymphatic tissues. Poster presented at: 9th Conference on Retroviruses and Opportunistic Infections (CROI); February 24-28, 2002; Seattle, WA. Poster 384-T. Available at: http://retroconference.org/2002/Posters/13864.pdf. Last accessed on May 23, 2013.
  17. Agarwal K, Fung SK, Nguyen TT, et al. Twenty-Eight Day Safety and Efficacy of Tenofovir Alafenamide (TAF) Fumarate in Chronic Hepatitis B (CHB) Patients. 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); November 1-5, 2013; Washington DC. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2013. Available at: http://www.natap.org/2013/AASLD/AASLD_91.htm. Last accessed on April 22, 2016.
  18. Gilead Sciences, Inc. Genvoya - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide fumarate tablet: Full Prescribing Information, November 2015. DailyMed. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34784acf-15ed-4715-b504-eb30430518e9. Last accessed on April 22, 2016.
  19. Ramanathan S, Wang H, Custodio J, Hepner-Harris M, Cheng A, Kearney BP. Lack of clinically relevant drug interactions between GS-7340 and efavirenz. Abstract presented at: 13th International Workshop on Clinical Pharmacology of HIV Therapy; March 16-18, 2012; Barcelona, Spain. Abstract P_09. Available at: http://regist2.virology-education.com/abstractbook/2012_3.pdf. Last accessed on April 22, 2016.
  20. Jin F, Fordyce M, Garner W, et al. Pharmacokinetics, metabolism and excretion of tenofovir alafenamide. Abstract presented at: 14th International Workshop on Clinical Pharmacology of HIV Therapy; April 22-24, 2013; Amsterdam, The Netherlands. Abstract O_08. Available at: http://regist2.virology-education.com/abstractbook/2013_3.pdf. Last accessed on April 22, 2016.
  21. 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 April 22, 2016.
  22. 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 April 22, 2016.
  23. 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 April 22, 2016.
  24. 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 April 22, 2016.                        
  25. 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 April 22, 2016.
  26. 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 April 22, 2016.
  27. Gilead website. Pipeline: HIV/AIDS. Available at: http://gilead.com/research/pipeline. Last accessed on April 22, 2016.
  28. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide 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: NCT02607956. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02607956. Last accessed on April 22, 2016.
  29. Gilead Sciences. A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02603107. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02603107. Last accessed on April 22, 2016.
  30. 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 April 22, 2016.
  31. 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 April 22, 2016.
  32. 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 April 22, 2016.        
  33. Lawson EB, Martin H, McCallister S, Shao Y, Vimal M, Kearney BP. Drug Interactions Between Tenofovir Alafenamide and HIV Antiretroviral Agents. 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_23.htm. Last accessed on April 22, 2016.
  34. Bam RA, Yant SR, Cihlar T. Tenofovir alafenamide is not a substrate for renal organic anion transporters (OATs) and does not exhibit OAT-dependent cytotoxicity. Antivir Ther. 2014 Apr 4. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24699134. Last accessed on April 22, 2016.
  35. Custodio J, Doyle E, Pang PS, et al. Lack of Drug Interactions between Boosted and Unboosted Tenofovir Alafenamide-based Antiretroviral Single Tablet Regimens (Emtricitabine/Rilpivirine/Tenofovir Alafenamide and Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide) and the anti-HCV Single Tablet Regimen Ledipasvir/Sofosbuvir. Oral abstract presented at: ID Week 2015; October 7-11, 2015; San Diego, CA. Abstract 727. Available at: https://idsa.confex.com/idsa/2015/webprogram/Paper53310.html. Last accessed on April 22, 2016.
  36. Lawson EB, Martin H, McCallister S, Shao Y, Vimal M, Kearney BP. Drug Interactions between Tenofovir Alafenamide and HIV Antiretroviral Agents. Abstract presented at: 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 5-9, 2014; Washington, DC. Abstract H-1012. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=d43f86d1-e2cd-4948-a76f-d621e985a233&cKey=744bc3a9-b277-4c3a-8cf1-cf9a664f03e5&mKey=%7b5D6B1802-E453-486B-BCBB-B11D1182D8BB%7d. Last accessed on April 22, 2016.


Last Reviewed: April 24, 2016

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