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Tenofovir Alafenamide  Audio icon

Other Names: GS-7340, prodrug of tenofovir, TAF, tenofovir alafenamide fumarate, TFV alafenamide
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 three different fixed-dose combination [FDC] tablets; one FDC tablet has completed a Phase II study, and two other FDC tablets are in Phase III testing)
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 and ClinicalTrials.gov3)
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.4-6

Tenofovir alafenamide is predominantly metabolized intracellularly to tenofovir primarily by cathepsin A. 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.7-9 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.10

Tenofovir alafenamide has also demonstrated in vitro and in vivo activity against hepatitis B virus (HBV).11,12

Half-life (T½): After oral administration of tenofovir alafenamide in fasted dogs, the tenofovir half-life was approximately 23.2 hours.5

Metabolism/Elimination: Cytochrome P450 3A (CYP3A)-mediated metabolism of tenofovir alafenamide is minor.13 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.14

Resistance: The potency and resistance profile of tenofovir alafenamide was previously assessed in vitro. Results indicated that tenofovir alafenamide and tenofovir DF had similar activity against HIV isolates from all clades and resistant isolates tested. Both tenofovir alafenamide and tenofovir DF selected for the K65R mutation. Tenofovir alafenamide, however, showed greater antiviral potency in vitro than tenofovir DF.15 

In viral breakthrough experiments that reflected TFV-DP intracellular concentration differences between tenofovir alafenamide and tenofovir DF/tenofovir, viruses carrying K65R, up to 4 thymidine analogue mutations (TAMs), the T69 insertion, or Q151M complex were fully inhibited by tenofovir alafenamide, but only partially inhibited by tenofovir DF/tenofovir. For viruses with the highest resistance (5 TAMs; >20 antiviral activity fold change [FC]), breakthrough of viral growth could not be prevented by either tenofovir alafenamide or tenofovir DF/tenofovir.16,17
 
In a Phase II study comparing the FDC tablet darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus cobicistat-boosted darunavir plus emtricitabine/tenofovir DF (DRV + COBI + FTC/TDF) in treatment-naive adults, six participants (5.8%) receiving D/C/F/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.18

In a separate Phase II study comparing the FDC tablet elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus elvitegravir/cobicistat/emtricitabine/tenofovir DF (Stribild) in treatment-naive adults, six participants total (three participants in each group) met criteria for resistance analysis through 48 weeks of treatment. On preliminary analysis, none of these participants assigned to E/C/F/TAF had resistance mutations detected, while mutations were detected in two participants receiving Stribild (one participant with M184V and K70E; one participant with M184V and E92Q).19
 


Dosing in Clinical Trials


Study Identifiers: GS-US-299-0102; NCT015658503
Phase: II
Study Purpose: 48-week safety and efficacy study comparing the single-tablet FDC regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus cobicistat-boosted darunavir plus emtricitabine/tenofovir DF (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:
  • darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 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 + emtrcitabine 200 mg/tenofovir DF 300 mg (Truvada), plus placebo to match D/C/F/TAF.3,18,20 
(See references cited above for information on study results.)

Study Identifiers: GS-US-292-0102; NCT0149789921
Phase: II
Study Purpose: 48-week safety and efficacy study comparing the single-tablet FDC regimens elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF; Stribild)
Study Population: HIV-infected, treatment-naive adults
Dosing: Treatments were administered orally and once daily. Matching placebo tablet(s) were administered to participants in each group. Participants were assigned to one of the following two groups:
  • elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200mg/tenofovir alafenamide 10 mg single-tablet regimen, plus placebo to match Stribild
  • elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200mg/ tenofovir disoproxil fumarate 300 mg single-tablet regimen (Stribild), plus placebo to match E/C/F/TAF.19,21,22 
(See references cited above for information on study results.)

Study Identifiers: GS-US-292-0104; NCT0178050623
Phase: III
Study Purpose: 96-week safety and efficacy study comparing the single-tablet FDC regimens elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF; Stribild)
Study Population: HIV-infected, treatment-naive adults
Dosing: Treatments are administered orally and once daily. Participants are assigned to one of the following two groups:
  • elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg single-tablet regimen, plus placebo to match Stribild
  • elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg single-table regimen (Stribild), plus placebo to match E/C/F/TAF.23

Study Identifiers: GS-US-292-0111; NCT0179744524
Phase: III
Study Purpose: 96-week safety and efficacy study comparing the single-tablet FDC regimens elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF; Stribild)
Study Population: HIV-infected, treatment-naive adults
Dosing: Treatments are administered orally and once daily. Participants are assigned to one of the following two groups:
  • elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg 
  • elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg (Stribild).24

Several other studies evaluating tenofovir alafenamide as part of a single-tablet FDC regimen for HIV treatment are ongoing. In addition, an emtricitabine/tenofovir alafenamide FDC tablet is being investigated in a Phase III study.25 

As a stand-alone agent, tenofovir alafenamide is currently being studied in Phase III trials for the treatment of chronic HBV infection.26,27 
 


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 D/C/F/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 D/C/F/TAF arm and worsening diarrhea and proximal renal tubulopathy in the DRV + COBI + FTC/TDF arm. Participants in the D/C/F/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 D/C/F/TAF than DRV + COBI + FTC/TDF. No fractures were reported in either group.18,20

In Study GS-US-292-0102, most adverse events were of mild to moderate severity. Adverse events occurring in at least 10% of participants in the E/C/F/TAF group included nausea, diarrhea, upper respiratory tract infection, fatigue, headache, and cough. No treatment-related serious adverse events or study discontinuations due to renal events occurred. No cases of renal tubulopathy occurred in either group. Participants receiving E/C/F/TAF experienced less change in eGFR, exploratory markers of renal tubulopathy, and spine and hip BMD than participants receiving E/C/F/TDF. No pathological fractures occurred in either group.19,22
 


Drug Interactions


Tenofovir alafenamide is a P-gp substrate and weak inhibitor of both OCT1 and MATE1. Tenofovir alafenamide does not interact with renal transporters OAT1 or OAT3.28,29

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.13

Because of inhibition of cathepsin A (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.4

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 emtricitabine/tenofovir alafenamide, in combination with other agents.28,30


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 October 31, 2014.
  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 October 31, 2014.
  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: 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 October 31, 2014.
  4. 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.
  5. 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 October 31, 2014.
  6. 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 October 31, 2014.
  7. 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 October 31, 2014.
  8. Herman BD and Sluis-Cremer N. Molecular Pharmacology of Nucleoside and Nucleotide HIV-1 Reverse Transcriptase Inhibitors. In: Gallelli D, ed.Pharmacology. InTech, DOI: 10.5772/32969; 2012: p 63-81. Available at: http://cdn.intechopen.com/pdfs-wm/32120.pdf. Last accessed on October 31, 2014.
  9. 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 October 31, 2014.
  10. 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 October 31, 2014.
  11. 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.
  12. 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 October 31, 2014.
  13. 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 October 31, 2014.
  14. 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 October 31, 2014.
  15. Callebaut C, Margot N, Miller M. Resistance and potency of GS-7340, a next-generation tenofovir prodrug. Abstract presented at: International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies; June 5-9, 2012; Sitges, Spain. Abstract 46. Available at: http://www.intmedpress.com/serveFile.cfm?sUID=8ed08ff3-8b0b-4cda-b481-30a670282653. Last accessed on October 31, 2014.
  16. Margot N, Liu Y, Babusis D, Miller MD, Callebaut C. Antiviral Activity of Tenofovir Alafenamide (TAF) against Major NRTI-Resistant Viruses: Improvement over TDF/TFV is Driven by Higher TFV-DP Loading in Target Cells. International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies; June 4-8, 2013; Toronto, Canada. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2013. Available at: http://www.natap.org/2013/ResisWksp/ResisWksp_04.htm. Last accessed on October 31, 2014.
  17. Margot N, Liu Y, Babusis D, Miller MD, Callebaut C. Antiviral activity of tenofovir alafenamide (TAF) against major NRTI-resistant viruses: improvement over TDF/TFV is driven by higher TFV-DP loading in target cells. Abstract presented at: International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies; June 4-8, 2013; Toronto, Canada. Abstract 23. Available at: http://www.intmedpress.com/serveFile.cfm?sUID=11ce9800-f660-437d-85e5-5a79b7f7f1f3. Last accessed on October 31, 2014.
  18. 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 October 31, 2014.
  19. Sax P, Brar I, Elion R, et al. 48 Week Study of Tenofovir Alafenamide (TAF) vs. Tenofovir Disoproxil Fumarate (TDF), Each in a Single Tablet Regimen (STR) with Elvitegravir, Cobicistat, and Emtricitabine [E/C/F/TAF vs. E/C/F/TDF] for Initial HIV Treatment. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 10-13, 2013; Denver, CO. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2013. Available at: http://www.natap.org/2013/ICAAC/ICAAC_54.htm. Last accessed on October 31, 2014.
  20. 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 October 31, 2014.
  21. Gilead Sciences. A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen in HIV 1 Infected, Antiretroviral Treatment-Naive Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 14, 2011. NLM Identifier: NCT01497899. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01497899. Last accessed on October 31, 2014.
  22. Sax P, Brar I, Elion R, et al. 48 Week Study of Tenofovir Alafenamide (TAF) vs. Tenofovir Disoproxil Fumarate (TDF), Each in a Single Tablet Regimen (STR) with Elvitegravir, Cobicistat, and Emtricitabine [E/C/F/TAF vs. E/C/F/TDF] for Initial HIV Treatment. Abstract presented at: 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 10-13, 2013; Denver, CO. Abstract H-1464d. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=cc7c2e8e-d70c-4d53-b850-d62af2c1fde6&cKey=4b81ee08-365f-4b8a-9e14-76c428c5c9df&mKey=%7b7DD36E88-52C3-4FF1-A5DF-1D00766558B8%7d. Last accessed on October 31, 2014.
  23. 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: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 16, 2013. NLM Identifier: NCT01780506. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01780506. Last accessed on October 31, 2014.
  24. 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: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 20, 2013. NLM Identifier: NCT01797445. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01797445. Last accessed on October 31, 2014.
  25. Gilead Sciences. A Phase 3, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Positive Subjects Who Are Virologically Suppressed on Regimens Containing FTC/TDF. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 22, 2014. NLM Identifier: NCT02121795. Available at: http://www.clinicaltrials.gov/ct2/show/NCT02121795. Last accessed on October 31, 2014.
  26. 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 October 31, 2014.
  27. 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 October 31, 2014.
  28. 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 October 31, 2014.
  29. 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 October 31, 2014.
  30. 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 October 31, 2014.

 


Last Reviewed: October 31, 2014

Last Updated: October 31, 2014


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