Tenofovir disoproxil fumarate: A nucleotide reverse transcriptase inhibitor for the treatment of HIV infection

Clinical Therapeutics

Volumn 24, Issue 10, 2002, Pages 1515-1548

  Fung, Horatio B ^a   Stone, Elizabeth A ^b   Piacenti, Frank J ^a  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b LONG ISLAND UNIVERSITY   (United States)

Author keywords

HIV infection; Nucleotide reverse transcriptase inhibitor; PMPA; Tenofovir; Tenofovir disoproxil fumarate

Indexed keywords

ABACAVIR; ADEFOVIR; ALANINE AMINOTRANSFERASE; AMYLASE; ANTIRETROVIRUS AGENT; ASPARTATE AMINOTRANSFERASE; CIDOFOVIR; CREATINE KINASE; DELAVIRDINE; DIDANOSINE; EFAVIRENZ; INDINAVIR; LAMIVUDINE; LOPINAVIR; NEVIRAPINE; PLACEBO; PLASMA PROTEIN; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; TENOFOVIR; TENOFOVIR DISOPROXIL; TRIACYLGLYCEROL; VIRUS RNA; ZALCITABINE; ZIDOVUDINE;

ABDOMINAL PAIN; ADULT; ANOREXIA; ANTIVIRAL ACTIVITY; ARTICLE; ASTHENIA; CLINICAL TRIAL; DEPRESSION; DIARRHEA; DISTRIBUTION VOLUME; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG TOLERABILITY; DRUG URINE LEVEL; DRUG WITHDRAWAL; FATIGUE; FATTY LIVER; FEMALE; FEVER; FLATULENCE; GLUCOSURIA; HEADACHE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERGLYCEMIA; HYPOPHOSPHATEMIA; INCIDENCE; KIDNEY TUBULE ACIDOSIS; LACTIC ACIDOSIS; LIPODYSTROPHY; MALE; METABOLIC DISORDER; MYOPATHY; NAUSEA; NEPHROTOXICITY; NEURITIS; NEUTROPENIA; NONHUMAN; PANCREATITIS; PERIPHERAL NEUROPATHY; PHOSPHORYLATION; PNEUMONIA; PROTEINURIA; SINUSITIS; UNITED STATES; VOMITING;

EID: 0036811720     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/S0149-2918(02)80058-3     Document Type: Article

References (70)

1. Mouton Y, Alfandari S, Valette M, et al, for the Federation National des Centres de Lutte contre le SIDA. Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. AIDS. 1997;11:F101-F105.
2. Palella FJ Jr, Delaney KM, Moorman AC, et al, for the HIV Outpatient Study Investigators. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338:853-860.
3. Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents (February 4, 2002). Available at: http://www.hivatis.org./guidelines/adult/May23_02/AAMay23.pdf. Accessed March 1, 2002.
4. Streicher HZ, Reitz MS Jr, Gallo RC. Human immunodeficiency viruses. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th Ed. New York: Churchill Livingstone; 2000:1874-1887.
5. Kuritzkes D. Fourth International Workshop on HIV Drug Resistance and Treatment Strategies. Available at: http//www.medscape.com/Medscape/HIV/journal/2000/v06.n03/mha0630.kuri/ mha0630.kuri-01.html. Accessed July 2, 2000.
6. Deeks SG. Reports from the 3rd International Workshop on Salvage Therapy for HIV Infection. Available at: http//www.medscape.com/Medscape/HIVjournal/2000/v06.n03/mha0510.deek/ mha0510.deek-01.html. Accessed November 14, 2000.
7. Flexner C. HIV-protease inhibitors. N Engl J Med. 1998;338:1281-1292.
8. Rosenwirth B, Bogers WM, Nieuwenhuis IG, et al. An anti-HIV strategy combining chemotherapy and therapeutic vaccination. J Med Primatol. 1999;28:195-205.
9. Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133:21-30.
10. Balzarini J, Holy A, Jindrich J, et al. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: Potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob Agents Chemother. 1993;37:332-338.
11. Zidek Z, Frankova D, Holy A. Macrophage activation by antiviral acyclic nucleoside phosphonates in dependence on priming immune stimuli. Int J Immunopharmacol. 2000;22:1121-1129.
12. De Clercq E. In search of a selective antiviral chemotherapy. Clin Microbiol Rev. 1997;10:674-693.
13. Naeger LK, Margot NA, Miller MD. Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: Analysis of enzyme processivity, chain-terminator removal and viral replication. Antiviral Ther. 2001;6:115-126.
14. Squires KE. An introduction to nucleoside and nucleotide analogues. Antiviral Ther. 2001;6(Suppl 3):1-14.
15. Deeks SG, Barditch-Crovo P, Lietman PS, et al. Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(phosphonomethoxy)propyl]adenine, a novel anti-HIV therapy, in HIV-infected adults. Antimicrob Agents Chemother. 1998;42:2380-2384.
16. Balzarini J, Vahlenkamp T, Egberink H, et al. Antiretroviral activities of acyclic nucleoside phosphonates [9-(2-phosphonylmethoxyethyl)adenine, 9-(2-phosphonylmethoxyethyl)guanine, (R)-9-(2-phosphonylmethoxypropyl)adenine, and MDL 74,968] in cell cultures and murine sarcoma virus-infected newborn NMRI mice. Antimicrob Agents Chemother. 1997;41:611-616.
17. Cihlar T, Ho ES, Lin DC, Mulato AS. Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs. Nucleosides Nucleotides Nucleic Acids. 2001;20:641-648.
18. Barriere S, Winslow D, Coakley D, Rooney J. Safety of adefovir dipivoxil in the treatment of HIV infection. In: Program and Abstracts of the XII World Conference on AIDS; June 28-July 3, 1998; Geneva, Switzerland. Abstract 12386.
19. Tsai CC, Follis KE, Sabo A, et al. Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science. 1995;270:1197-1199.
20. Cohen J. AIDS research. New drug shows promise in monkeys. Science. 1995;270:1121-1122.
21. Viread® [package insert]. Foster City, Calif: Gilead Sciences, Inc; 2001.
22. Brinkman K, ter Hofstede HJ, Burger DM, et al. Adverse effects of reverse transcriptase inhibitors: Mitochondrial toxicity as common pathway. AIDS. 1998;12:1735-1744.
23. Zidek Z, Holy A, Frankova D. Antiretroviral agent (R)-9-(2-phosphonomethoxypropyl)adenine stimulates cytokine and nitric oxide production. Eur J Pharmacol. 1997;331:245-252.
24. Zidek Z, Frankova D, Holy A. Activation by 9-(R)-[2-(phosphonomethoxy)propyl] adenine of chemokine (RANTES, macrophage inflammatory protein 1α) and cytokine (tumor necrosis factor alpha, interleukin-10 [IL-10], IL-1β) production. Antimicrob Agents Chemother. 2001;45:3381-3386.
25. Srinivas RV, Fridland A. Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl)PMPA against various drug-resistant human immunodeficiency virus strains. Antimicrob Agents Chemother. 1998;42:1484-1487.
26. Robbins BL, Srinivas RV, Kim C, et al. Anti-human immunodeficiency virus activity and cellular metabolism of a potential prodrug of the acyclic nucleoside phosphonate 9-R-(2-phosphonomethoxypropyl)adenine (PMPA), bis(isopropyloxymethylcarbonyl)PMPA. Antimicrob Agents Chemother. 1998;42:612-617.
27. Shaw JP, Sueoka CM, Oliyai R, et al. Metabolism and pharmacokinetics of novel oral prodrugs of 9-[(R)-2-(phosphonomethoxy)propyl]adenine (PMPA) in dogs. Pharm Res. 1997;14:1824-1829.
28. Cundy KC, Sueoka C, Lynch GR, et al. Pharmacokinetics and bioavailability of the anti-human immunodeficiency virus nucleotide analog 9-[(R)-2-(phosphonomethoxy)propyl] adenine (PMPA) in dogs. Antimicrob Agents Chemother. 1998;42:687-690.
29. Barditch-Crovo P, Deeks SG, Collier A, et al. Phase i/ii trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults. Antimicrob Agents Chemother. 2001;45:2733-2739.
30. Kearney BP, Gill SC, Flaherty JF, et al. Effect of demographic variable on the pharmacokinetics of tenofovir DF in HIV-infected patients and healthy subjects. In: Program and Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2001; Chicago, Ill. Abstract 504.
31. FDA Advisory Committee Briefing Document: Viread™ (Tenofovir DF) for the Treatment of HIV-1 Infection in Adults in Combination with Other Antiretroviral Agents. NDA 21-356. Gilead Sciences, Inc; August 30, 2001. Available at: http://www.fda.gov/ohrms/dockets/ac/01/briefing/3792b1_01_gilead.pdf. Accessed April 10, 2002.
32. Mulato AS, Cherrington JM. Anti-HIV activity of adefovir (PMEA) and PMPA in combination with antiretroviral compounds: In vitro analyses. Antiviral Res. 1997;36:91-97.
33. Cherrington J, Mulato AS. Adefovir (PMEA) and PMPA show synergistic or additive inhibition of HIV replication in vitro in combination with other anti-HIV agents. In: Program and Abstracts of the 12th World Conference on AIDS; June 28-July 3, 1998; Geneva, Switzerland. Abstract 41195.
34. Hossain M, Margolis D. Low concentrations of mycophenolic acid augment the antiretroviral activity of abacavir, didanosine, tenofovir and the combination of abacavir and didanosine in vitro. In: Program and Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; February 4-8, 2001; Chicago, Ill. Abstract 307.
35. Palmer S, Shafer RW, Merigan TC. Hydroxyurea enhances the activities of didanosine, 9-[2-(phosphonylmethoxy)ethyl] adenine, and 9-[2-(phosphonylmethoxy) propyl]adenine against drug-susceptible and drug-resistant human immunodeficiency virus isolates. Antimicrob Agents Chemother. 1999;43:2046-2050.
36. Deeks SG, Barditch-Crovo P, Collier A, et al. Hydroxyurea does not enhance the anti-HIV activity of low-dose tenofovir disoproxil fumarate. J Acquired Immune Defic Syndr. 2001;28:336-339.
37. Tsai CC, Follis KE, Beck TW, et al. Effects of (R)-9-(2-phosphonylmethoxypropyl)adenine monotherapy on chronic SIV infection in macaques. AIDS Res Hum Retroviruses. 1997;13:707-712.
38. van Rompay KK, Dailey PJ, Tarara RP, et al. Early short-term 9-[2-(R)-(phosphonomethoxy)propyl]adenine treatment favorably alters the subsequent disease course in simian immunodeficiency virus-infected newborn Rhesus macaques. J Virol. 1999;73:2947-2955.
39. Kumar A, Bischofberger N, Lifson J, Narayan O. Development of virus specific immune responses in SHIVKU infected macaques treated with PMPA. In: Program and Abstracts of the 13th International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract MoOrA101.
40. Schooley RT, Ruane P, Myers RA, et al. Tenofovir DF in antiretroviral-experienced patients: Results from a 48-week, randomized, double-blind study. AIDS. 2002;16:1257-1263.
41. Schooley R, Myers R, Ruane P, et al. A double-blind placebo-controlled study of tenofovir disoproxil fumarate for the treatment of HIV infection. In: Program and Abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 26-29, 1999; San Francisco, Calif. Abstract LB-19.
42. Squires K, Pierone G, Berger D, et al. Tenofovir DF: A 24-week interim analysis from a phase III double-blind placebo-controlled study in antiretroviral experienced patients. In: Program and Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2001; Chicago, Ill. Abstract 666.
43. Squires K, Pierone G, Berger D, et al. Tenofovir DF: A 48-week final analysis from a phase III randomized double-blind placebo-controlled study in antiretroviral experienced patients. In: Program and Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Wash. Abstract 413-W.
44. Louie M, Hogan C, Hurley A, et al. Determining the relative efficacy of tenofovir DF using frequent measurements of HIV-RNA during a short course of monotherapy in antiretroviral drug naive individuals. In: Program and Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Wash. Abstract 3.
45. FDA Antiviral Drugs Advisory Committee meeting on NDA 21-356, Viread. October 3, 2001. Available at: http://www.fda.gov/ohrms/dockets/ac/01/transcripts/3792t1.htm. Accessed April 10, 2002.
46. Schooley R, Ruane P, Myers R, et al. Tenofovir DF: An interim analysis of the open label extension phase from a 48-week randomized double-blind placebo-controlled study in antiretroviral experienced patients. In: Program and Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2001; Chicago, Ill. Abstract 1929.
47. Coakley D, Lamy P, Cheng A, et al. Tenofovir DF 300 mg consistently demonstrates anti-HIV activity regardless of baseline demographic characteristics in antiretroviral-experienced HIV-1-infected patients. In: Program and Abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV Infection; October 28-31, 2001; Athens, Greece. Abstract 56.
48. Follansbee S, Reynes J, Nelson M, et al. The Viread Expanded Access Program: Safety and efficacy of tenofovir disoproxil fumarate in antiretroviral treatment-experienced patients. In: Program and Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Wash. Abstract 415-W.
49. Ying C, De Clercq E, Nicholson W, et al. Inhibition of the replication of the DNA polymerase M550V mutation variant of human hepatitis B virus by adefovir, tenofovir, L-FMAU, DAPD, penciclovir and lobucavir. J Viral Hepat. 2000;7:161-165.
50. Bochet M, Tubiana R, Benhamou Y, et al. Tenofovir disoproxil fumarate suppresses lamivudine-resistant HBV replication in patients co-infected with HIV/HBV. In: Program and Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Wash. Abstract 675-M.
51. Cooper D, Cheng A, Coakley D, et al. Anti-HBV activity of tenofovir DF in HIV/HBV co-infected patients. In: Program and Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Wash. Presentation 124.
52. Gazzard BG. The potential place of tenofovir in antiretroviral treatment regimens. Int J Clin Pract. 2001;55:704-709.
53. Wainberg MA, Miller MD, Quan Y, et al. In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Antiviral Ther. 1999;4:87-94.
54. Harrigan PR, Miller MD, McKenna P, et al. Phenotypic susceptibilities to tenofovir in a large panel of clinically derived human immunodeficiency virus type 1 isolates. Antimicrob Agents Chemother. 2002;46:1067-1072.
55. Miller MD, Margot NA, Hertogs K, et al. Antiviral activity of tenofovir (PMPA) against nucleoside-resistant clinical HIV samples. Nucleosides Nucleotides Nucleic Acids. 2001;20:1025-1028.
56. Hertogs K, De Vroey V, Van Den Eynde C, et al. Common rare and new HIV-1 resistance profiles observed in routine clinical practice: A survey of over 5,000 isolates and the characterization of novel 3TC resistance mutational profile lacking 184V. In: Program and Abstracts of the 7th Conference on Retroviruses and Opportunistic Infections; January 30-February 4, 2000; San Francisco, Calif. Abstract 740.
57. Miller MD, Margot N, Coakley D, Cheng A. Anti-HIV responses and development of RT mutations in antiretroviral-experienced patients adding tenofovir DF therapy: Baseline and week-24 genotypic analyses of study 907. In: Program and Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2001; Chicago, Ill. Abstract 1928.
58. Margot NA, Johnson A, Cheng A, et al. Final 48-week genotypic and phenotypic analyses of study 907: Tenofovir DF added to stable background regimens. In: Program and Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Wash. Abstract 414-W.
59. Struble K, Piscitelli SC. Syndromes of abnormal fat redistribution and metabolic complications in HIV-infected patients. Am J Health Syst Pharm. 1999;56:2343-2348.
60. Birkus G, Hitchcock MJ, Cihlar T. Assessment of mitochondrial toxicity in human cells treated with tenofovir: Comparison with other nucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2002;46:716-723.
61. Cihlar T, Birkus G, Greenwalt DE, Hitchcock MJ. Tenofovir exhibits low cytotoxicity in various human cell types: Comparison with other nucleoside reverse transcriptase inhibitors. Antiviral Res. 2002;54:37-45.
62. Tebas P, Powderly WG, Claxton S, et al. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS. 2000;14:F63-F67.
63. Mora S, Sala N, Bricalli D, et al. Bone mineral loss through increased bone turnover in HIV-infected children treated with highly active antiretroviral therapy. AIDS. 2001;15:1823-1829.
64. Becker S, Ruane P, Cimoch P, et al. Safety profile of tenofovir disoproxil fumarate in patients with advanced HIV disease. In: Program and Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2001; Chicago, Ill. Abstract 1930.
65. Cheng A, Barriere S, Coakley DF, et al. Safety profile of tenofovir DF in antiretroviral-experienced patients from randomized double-blind placebo-controlled clinical trials. In: Program and Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Wash. Abstract 416-W.
66. McGowan I, Cheng A, Coleman S, et al. Assessment of bone mineral density in HIV-infected antiretroviral therapy-naive patients. In: Program and Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; February 4-8, 2001; Chicago, Ill. Abstract 628.
67. Ho ES, Lin DC, Mendel DB, Cihlar T. Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J Am Soc Nephrol. 2000;11:383-393.
68. Cheng A, Barriere S, Coakley D, et al. Safety profile of tenofovir DF in treatment-experienced patients from randomized placebo-controlled clinical trials. In: Program and Abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV Infection; October 28-31, 2001; Athens, Greece. Abstract 227.
69. Kearney BP, Flaherty J, Wolf J, et al. Lack of clinically relevant drug-drug interactions between tenofovir DF and efavirenz, indinavir, lamivudine and lopinavir/ritonavir in healthy subjects. In: Program and Abstracts of the 8th European Conference on Clinical Aspects and Treatment of HIV Infection; October 28-31, 2001; Athens, Greece. Abstract 171.
70. Flaherty J, Kearney B, Wolf J, et al. Coadministration of tenofovir DF and didanosine: A pharmacokinetic and safety evaluation. In: Program and Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2001; Chicago, Ill. Abstract 1729.