Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: A randomized phase 2 study

Journal of Acquired Immune Deficiency Syndromes

Volumn 67, Issue 1, 2014, Pages 52-58

  Sax, Paul E ^a   Zolopa, Andrew ^b   Brar, Indira ^c   Elion, Richard ^d   Ortiz, Roberto ^e   Post, Frank ^f   Wang, Hui ^g   Callebaut, Christian ^g   Martin, Hal ^g   Fordyce, Marshall W ^g   McCallister, Scott ^g  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b STANFORD UNIVERSITY   (United States)

^c HENRY FORD HOSPITAL   (United States)

^d GEORGE WASHINGTON UNIVERSITY HOSPITAL   (United States)

^e ORLANDO IMMUNOLOGY CENTER   (United States)

^f KING'S COLLEGE LONDON   (United Kingdom)

^g GILEAD SCIENCES   (United States)

Author keywords

clinical trials; elvitegravir; GS 7340; stribild; tenofovir alafenamide

Indexed keywords

ALANINE AMINOTRANSFERASE; AMYLASE; ASPARTATE AMINOTRANSFERASE; CHOLESTEROL; COBICISTAT PLUS ELVITEGRAVIR PLUS EMTRICITABINE PLUS TENOFOVIR ALAFENAMIDE; COBICISTAT PLUS ELVITEGRAVIR PLUS EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; CREATINE KINASE; GAMMA GLUTAMYLTRANSFERASE; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; TENOFOVIR ALAFENAMIDE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; VIRUS RNA; ADENINE; CREATININE; GS-7340; PRODRUG;

ABNORMAL DREAMING; ABNORMAL LABORATORY RESULT; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALBUMINURIA; ALLERGY; AMYLASE BLOOD LEVEL; ANXIETY DISORDER; AREA UNDER THE CURVE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BACKACHE; BONE DENSITY; BRONCHITIS; CD4 LYMPHOCYTE COUNT; CONDYLOMA ACUMINATUM; CONFERENCE PAPER; CONJUNCTIVITIS; CONTROLLED STUDY; COUGHING; CREATINE KINASE BLOOD LEVEL; CREATININE CLEARANCE; DEPRESSION; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEMALE; FLATULENCE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GASTROINTESTINAL SYMPTOM; GLUCOSE BLOOD LEVEL; HEADACHE; HEMATURIA; HIP; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HYPERCHOLESTEROLEMIA; HYPOPHOSPHATEMIA; INFLUENZA; INSOMNIA; LIMB PAIN; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; NECK PAIN; NEUTROPENIA; PARESTHESIA; PHARYNGITIS; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN URINE LEVEL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL; RASH; RHINOPHARYNGITIS; SINGLE TABLET REGIMEN; SINUSITIS; SKIN PAPILLOMA; SPINE; SYPHILIS; TABLET FORMULATION; TREATMENT DURATION; TREATMENT OUTCOME; TRIACYLGLYCEROL BLOOD LEVEL; UPPER RESPIRATORY TRACT INFECTION; VIRUS LOAD; VOMITING; ANALOGS AND DERIVATIVES; BLOOD; CLINICAL TRIAL; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS 1; ISOLATION AND PURIFICATION; METABOLISM; ORAL DRUG ADMINISTRATION; PHOTON ABSORPTIOMETRY; UNITED STATES; URINE; VIROLOGY;

ABSORPTIOMETRY, PHOTON; ADENINE; ADMINISTRATION, ORAL; ADULT; BONE DENSITY; CD4 LYMPHOCYTE COUNT; CHOLESTEROL; CREATININE; DOUBLE-BLIND METHOD; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; MALE; PRODRUGS; PROTEINURIA; RNA, VIRAL; UNITED STATES;

EID: 84906080271     PISSN: 15254135     EISSN: 10779450     Source Type: Journal    
DOI: 10.1097/QAI.0000000000000225     Document Type: Conference Paper

References (41)

1. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338: 853-860.
2. Mocroft A, Vella S, Benfield TL, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet. 1998;352:1725-1730.
3. Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med. 2009;360:1815-1826.
4. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493-505.
5. Mayer K, Gazzard B, Zuniga JM, et al. Controlling the HIV epidemic with antiretrovirals: IAPAC consensus statement on treatment as prevention and preexposure prophylaxis. J Int Assoc Provid AIDS Care. 2013;12:208-216.
6. Wood E, Milloy MJ, Montaner JS. HIV treatment as prevention among injection drug users. Curr Opin HIV AIDS. 2012;7:151-156.
7. Capeau J. Premature aging, premature age-related comorbidities in HIV-infected patients: facts and hypotheses. Clin Infect Dis. 2011;53: 1127-1129.
8. Centers for Disease Research. HIV/AIDS Surveillance Report 2005. 17th ed. Atlanta; 2007: 1-54.
9. Guaraldi G, Zona S, Menozzi M, et al. Cost of noninfectious comorbid-ities in patients with HIV. Clinicoecon Outcomes Res. 2013;5:481-488.
10. Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbid-ities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011;53:1120-1126.
11. US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of anti-retrovira agents in HIV-1 infected adults and adolescents. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL. pdf. 2013. Accessed October 15, 2013.
12. Chesney MA. Factors affecting adherence to antiretroviral therapy. Clin Infect Dis. 2000;30(suppl 2):S171-S176.
13. Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a difference? Curr Med Res Opin. 2014;30:89-97.
14. Sterrantino G, Santoro L, Bartolozzi D, et al. Self-reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era. Patient Prefer Adherence. 2012;6:427-433.
15. Hall AM, Hendry BM, Nitsch D, et al. Tenofovir-Associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011;57:773-780.
16. Post FA, Moyle GJ, Stellbrink HJ, et al. Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr. 2010;55:49-57.
17. VIREAD (Tenofovir Disoproxil Fumarate) Tablets and Powder. US Prescribing Information. Foster City CA: CGSI; 2012.
18. Stellbrink HJ, Orkin C, Arribas JR, et al. Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis. 2010;51:963-972.
19. Schafer JJ, Manlangit K, Squires KE. Bone health and human immunodeficiency virus infection. Pharmacotherapy. 2013;33:665-682.
20. Lee WA, He GX, Eisenberg E, et al. Selective intracellular activation of a novel prodrug of the human immunodeficiency virus reverse transcrip-tase inhibitor tenofovir leads to preferential distribution and accumulation in lymphatic tissue. Antimicrob Agents Chemother. 2005;49:1898-1906.
21. 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;74:92-100.
22. Birkus G, Wang R, Liu X, et al. Cathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131. Antimicrob Agents Chemother. 2007;51:543-550.
23. Van Rompay KK, Durand-Gasselin L, Brignolo LL, et al. Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virolog-ical effects. Antimicrob Agents Chemother. 2008;52:3144-3160.
24. Poizot-Martin I, Solas C, Allemand J, et al. Renal impairment in patients receiving a tenofovir-cART regimen: impact of tenofovir trough concentration. J Acquir Immune Defic Syndr. 2013;62:375-380.
25. Rodriguez-Novoa S, Labarga P, D'Avolio A, et al. Impairment in kidney tubular function in patients receiving tenofovir is associated with higher tenofovir plasma concentrations. AIDS. 2010;24:1064-1066.
26. Ray AS, Cihlar T, Robinson KL, et al. Mechanism of active renal tubular efflux of tenofovir. Antimicrob Agents Chemother. 2006;50:3297-3304.
27. 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; ePub ahead of print, April 4, 2014, 10.3851/IMP2770.
28. 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;63:449-455.
29. Margot N, Liu Y, Babusis D, Miller MD, et al. Antiviral activity of teno-fovir alafenamide (TAF) against major NRTI-resistant viruses: improvement over TDF/TFV is driven by higher TFV-DP loading in target cells. Paper presented at: International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies. Toronto, Canada: 2013.
30. Lepist EI, Phan TK, Roy A, et al. Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro. Antimicrob Agents Chemother. 2012;56: 5409-5413.
31. Ramanathan SWX, Custodio J, Wang H, et al. Pharmacokinetics of a novel EVG/COBI/TFC/GS-7340 single tablet regimen. Paper presented at: 13th International Workshop on Clinical Pharmacology of HIV Therapy. Barcelona, Spain: 2012.
32. Smith FH, Soon T, Zhou G, et al. A meta-Analysis to assess the FDA DAVP's TLOVR algorithm in HIV submissions. Drug Inf J. 2011;45: 291-300.
33. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of The National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment panel III). JAMA. 2001;285:2486-2497.
34. McComsey GA, Kitch D, Daar ES, et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abaca-vir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203:1791-1801.
35. DeJesus E, Rockstroh JK, Henry K, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and teno-fovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012;379: 2429-2438.
36. Sax PE, DeJesus E, Mills A, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricita-bine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379:2439-2448.
37. German P, Liu HC, Szwarcberg J, et al. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J Acquir Immune Defic Syndr. 2012;61:32-40.
38. Hall AM, Edwards SG, Lapsley M, et al. Subclinical tubular injury in HIV-infected individuals on antiretroviral therapy: a cross-sectional analysis. Am J Kidney Dis. 2009;54:1034-1042.
39. Post FA, Wyatt CM, Mocroft A. Biomarkers of impaired renal function. Curr Opin HIV AIDS. 2010;5:524-530.
40. Behrens G, Maserati R, Rieger A, et al. Switching to tenofovir/emtrici- tabine from abacavir/lamivudine in HIV-infected adults with raised cholesterol: effect on lipid profiles. Antivir Ther. 2012;17:1011-1020.
41. Tungsiripat M, Kitch D, Glesby MJ, et al. A pilot study to determine the impact on dyslipidemia of adding tenofovir to stable background antire-troviral therapy: ACTG 5206. AIDS. 2010;24:1781-1784.