Anti-HIV-1 activity of leflunomide: A comparison with mycophenolic acid and hydroxyurea

AIDS

Volumn 17, Issue 11, 2003, Pages 1613-1620

  Schläpfer, Erika ^a   Fischer, Marek ^a   Ott, Peter ^b   Speck, Roberto F ^a,b  

^a Hospital Epidemiology   (Switzerland)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

Antiretroviral therapy; HIV; Hydroxyurea; Leflunomide; Mycophenolic acid

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CD4 ANTIGEN; DIHYDROOROTATE DEHYDROGENASE; HYDROXYUREA; IMMUNOMODULATING AGENT; LEFLUNOMIDE; MYCOPHENOLIC ACID; URIDINE; VIRUS RNA;

ANTIVIRAL ACTIVITY; ARTICLE; BLOOD CELL; CANCER SURVIVAL; CELL LABELING; CELL SELECTION; CELL SURVIVAL; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; FLUORESCENCE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN TISSUE; INHIBITION KINETICS; LYMPHOCYTE; MOLECULAR MECHANICS; MONONUCLEAR CELL; PRIORITY JOURNAL; TONSIL CELL; VIRUS REPLICATION;

ANTI-HIV AGENTS; CD4-POSITIVE T-LYMPHOCYTES; CELL SURVIVAL; CELLS, CULTURED; DNA, VIRAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG COMBINATIONS; FLOW CYTOMETRY; HIV-1; HUMANS; HYDROXYUREA; ISOXAZOLES; LEUKOCYTES, MONONUCLEAR; MYCOPHENOLIC ACID;

EID: 0042128295     PISSN: 02699370     EISSN: None     Source Type: Journal    
DOI: 10.1097/00002030-200307250-00005     Document Type: Article

References (59)

1. Detels R, Tarwater P, Phair JP, Margolick J, Riddler SA, Munoz A. Effectiveness of potent antiretroviral therapies on the incidence of opportunistic infections before and after AIDS diagnosis. AIDS 2001, 15:347-355.
2. Palella FJ, Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, 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.
3. Ives NJ, Gazzard BG, Easterbrook PJ. The changing pattern of AIDS-defining illnesses with the introduction of highly active antiretroviral therapy (HAART) in a London clinic. J Infect 2001, 42:134-139.
4. Kartsonis NA, D'Aquila RT. Clinical monitoring of HIV-1 infection in the ERA of antiretroviral resistance testing. Infect Dis Clin North Am 2000, 14:879-899.
5. Richman DD. HIV chemotherapy. Nature 2001, 410;995-1001.
6. Stenzel MS, Carpenter CC. The management of the clinical complications of antiretroviral therapy. Infect Dis Clin North Am 2000, 14:851-178, vi.
7. Andrews L, Friedland G. Progress in HIV therapeutics and the challenges of adherence to antiretroviral therapy. Infect Dis Clin North Am 2000, 14:901-928.
8. Keiser P, Nassar N, Kvanli MB, Turner D, Smith JW, Skiest D. Long-term impact of highly active antiretroviral therapy on HIV-related health care costs. J Acquir Immune Defic Syndr 2001, 27:14-19.
9. Gao WY, Cara A, Gallo RC, Lori F. Low levels of deoxynucleotides in peripheral blood lymphocytes: a strategy to inhibit human immunodeficiency virus type 1 replication. Proc Natl Acad Sci USA 1993, 90:8925-8928.
10. Ravot E, Lisziewicz J, Lori F. New uses for old drugs in HIV infection: the role of hydroxyurea, cyclosporin and thalidomide. Drugs 1999, 58:953-963.
11. Ichimura H, Levy JA. Polymerase substrate depletion: a novel strategy for inhibiting the replication of the human immuno-deficiency virus. Virology 1995, 211:554-560.
12. Gao WY, Johns DG, Mitsuya H. Anti-human immunodeficiency virus type 1 activity of hydroxyurea in combination with 2′,3′-dideoxynucleosides. Mol Pharmacol 1994, 46:767-772.
13. Hartman NR, Ahluwalia GS, Cooney DA, Mitsuya H, Kageyama S, Fridland A, et al. Inhibitors of IMP dehydrogenase stimulate the phosphorylation of the anti-human immunodeficiency virus nucleosides 2′,3′-dideoxyadenosine and 2′,3′-dideoxyinosine. Mol Pharmacol 1991, 40:118-124.
14. Szekeres T, Fritzer-Szekeres M, Elford HL. The enzyme ribonucleotide reductase: target for antitumor and anti-HIV therapy. Crit Rev Clin Lab Sci 1997, 34:503-528.
15. Natsumeda Y, Carr SF. Human type I and II IMP dehydrogenases as drug targets. Ann N Y Acad Sci 1993, 696:88-93.
16. Hellinger JA, Iwane MK, Smith JJ, Fleishman AN, Torres RA, Schrader S, et al. A randomized study of the safety and antiretroviral activity of hydroxyurea combined with didanosine in persons infected with human immunodeficiency virus type 1. American Foundation for AIDS Research Community-Based Clinical Trials Network. J Infect Dis 2000, 181:540-547.
17. Zala C, Salomon H, Ochoa C, Kijak G, Federico A, Perez H, et al. Higher rate of toxicity with no increased efficacy when hydroxyurea is added to a regimen of stavudine plus didanosine and nevirapine in primary HIV infection. J Acquir Immune Defic Syndr 2002, 29:368-373.
18. Lafeuillade A, Poggi C, Chadapaud S, Hittinger G, Khiri H, Halfon P. Impact of immune interventions on proviral HIV-1 DNA decay in patients receiving highly active antiretroviral therapy. HIV Med 2001, 2:189-194.
19. Rodriguez CG, Vila J, Capurro AF, Maidana MM, Boffo Lissin LD. Combination therapy with hydroxyurea versus without hydroxyurea as first line treatment options for antiretroviral-naive patients. HIV Clin Trials 2000, 1:1-8.
20. Clotet B, Ruiz L, Cabrera C, Ibanez A, Canadas MP, Sirera G, et al. Short-term anti-HIV activity of the combination of didanosine and hydroxyurea. Antivir Ther 1996, 1:189-193.
21. Biron F, Ponceau B, Bouhour D, Boibieux A, Verrier B, Peyramond D. Long-term safety and antiretroviral activity of hydroxyurea and didanosine in HIV-infected patients. J Acquir Immune Defic Syndr 2000, 25:329-336.
22. Lori F, Jessen H, Lieberman J, Finzi D, Rosenberg E, Tinelli C, et al. Treatment of human immunodeficiency virus infection with hydroxyurea, didanosine, and a protease inhibitor before sero-conversion is associated with normalized immune parameters and limited viral reservoir. J Infect Dis 1999, 180:1827-1832.
23. Rutschmann OT, Vernazza PL, Bucher HC, Opravil M, Ledergerber B, Telenti A, et al. Long-term hydroxyurea in combination with didanosine and stavudine for the treatment of HIV-1 infection. Swiss HIV Cohort Study. AIDS 2000, 14:2145-2151.
24. Havlir DV, Gilbert PB, Bennett K, Collier AC, Hirsch MS, Tebas P, et al. Effects of treatment intensification with hydroxyurea in HIV-infected patients with virologic suppression. AIDS 2001, 15:1379-1388.
25. Coull JJ, Turner D, Melby T, Betts MR, Lanier R, Margolis DM. A pilot study of the use of mycophenolate mofetil as a component of therapy for multidrug-resistant HIV-1 infection. J Acquir Immune Defic Syndr 2001, 26:423-434.
26. Press N, Kimel G, Harris M, Yip B, Craib KJ, Montaner JS. Case series assessing the safety of mycophenolate as part of multidrug rescue treatment regimens. HIV Clin Trials 2002, 3:17-20.
27. Chapuis AG, Paolo RG, D'Agostino C, Attinger A, Knabenhans C, Fleury S, et al. Effects of mycophenolic acid on human immuno-deficiency virus infection in vitro and in vivo. Nat Med 2000, 6:762-768.
28. Lafeuillade A, Hittinger G, Chadapaud S, Maillefet S, Rieu A, Poggi C. The HYDILE trial: efficacy and tolerance of a quadruple combination of reverse transcriptase inhibitors versus the same regimen plus hydroxyurea or hydroxyurea and interleukin-2 in HIV-infected patients failing protease inhibitor-based combinations. HIV Clin Trials 2002, 3:263-271.
29. Simonelli C, Nasti G, Vaccher E, Tirelli U, Zanussi S, de Paoli P, et al. Hydroxyurea treatment in HIV-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol 1996, 13:462-464.
30. Giacca M, Zanussi S, Comar M, Simonelli C, Vaccher E, de Paoli P, et al. Treatment of human immunodeficiency virus infection with hydroxyurea: virologic and clinical evaluation. J Infect Dis 1996, 174:204-209.
31. Sousa AE, Carneiro J, Meier-Schellersheim M, Grossman Z, Victorino RM. CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J Immunol 2002, 169:3400-3406.
32. Prakash A, Jarvis B. Leflunomide: a review of its use in active rheumatoid arthritis. Drugs 1999, 58:1137-1164.
33. Hermann E, Idziorek T, Kusnierz JP, Mouton Y, Capron A, Bahr GM. Role of nitric oxide in the regulation of lymphocyte apoptosis and HIV-1 replication. Int J Immunopharmacol 1997, 19:387-397.
34. Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA. The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase. Biochemistry 1996, 35:1270-1273.
35. Ruckemann K, Fairbanks LD, Carrey EA, Hawrylowicz CM, Richards DF, Kirschbaum B, et al. Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humans. J Biol Chem 1998, 273:21682-21691.
36. Fairbanks LD, Bofill M, Ruckemann K, Simmonds HA. Importance of ribonucleotide availability to proliferating T- lymphocytes from healthy humans. Disproportionate expansion of pyrimidine pools and contrasting effects of de novo synthesis inhibitors. J Biol Chem 1995, 270:29682-29689.
37. Herrmann ML, Schleyerbach R, Kirschbaum BJ. Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology 2000, 47:273-289.
38. Breedveld FC, Dayer JM. Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis 2000, 59:841-849.
39. Korin YD, Zack JA. Progression to the G1b phase of the cell cycle is required for completion of human immunodeficiency virus type 1 reverse transcription in T cells. J Virol 1998, 72:3161-3168.
40. Greene WC, Peterlin BM. Charting HIV's remarkable voyage through the cell: basic science as a passport to future therapy. Nat Med 2002, 8:673-680.
41. Moore JP, McKeating JA, Weiss RA, Sattentau QJ. Dissociation of gp120 from HIV-1 virions induced by soluble CD4. Science 1990, 250:1139-1142.
42. Christopherson C, Kidane Y, Conway B, Krowka J, Sheppard H, Kwok S. PCR-Based assay to quantify human immunodeficiency virus type 1 DNA in peripheral blood mononuclear cells. J Clin Microbiol 2000, 38:630-634.
43. Bisset LR, Bosbach S, Tomasik Z, Lutz H, Schupbach J, Boni J. Quantification of in vitro retroviral replication using a one-tube real- time RT-PCR system incorporating direct RNA preparation. J Virol Meth 2001, 91:149-155.
44. Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, Rabson A, et al. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol 1986, 59:284-291.
45. Johnson HJ, Swan SK, Heim-Duthoy KL, Nicholls AJ, Tsina I, Tarnowski T. The pharmacokinetics of a single oral dose of mycophenolate mofetil in patients with varying degrees of renal function. Clin Pharmacol Ther 1998, 63:512-518.
46. Luzzati R, Di Perri G, Fendt D, Ramarli D, Broccali G, Concia E. Pharmacokinetics, safety and anti-human immunodeficiency virus (HIV) activity of hydroxyurea in combination with didanosine. J Antimicrob Chemother 1998, 42:565-566.
47. Villani P, Maserati R, Regazzi MB, Giacchino R, Lori F. Pharmacokinetics of hydroxyurea in patients infected with human immunodeficiency virus type I. J Clin Pharmacol 1996, 36:117-121.
48. Hossain MM, Margolis DM. Inhibition of HIV replication by A77 1726, the active metabolite of leflunomide, in combination with pyrimidine nucleoside reverse transcriptase inhibitors. J Acquir Immune Defic Syndr 2001, 28:199-201.
49. Mills GC, Schmalstieg FC, Trimmer KB, Goldman AS, Gordblum RM. Purine metabolism in adenosine deaminase deficiency. Proc Natl Acad Sci USA 1976, 73:2867-2871.
50. Heredia A, Margolis D, Oldach D, Hazen R, Le N, Redfield R. Abacavir in combination with the inosine monophosphate dehydrogenase (IMPDH)-inhibitor mycophenolic acid is active against multidrug- resistant HIV-1. J Acquir Immune Defic Syndr 1999, 22:406-407.
51. Daxecker H, Raab M, Cichna M, Markl P, Muller MM. Determination of the effects of mycophenolic acid on the nucleotide pool of human peripheral blood mononuclear cells in vitro by high- performance liquid chromatography. Clin Chim Acta 2001, 310:81-87.
52. Glushakova S, Baibakov B, Margolis LB, Zimmerberg J. Infection of human tonsil histocultures: a model for HIV pathogenesis. Nat Med 1995, 1:1320-1322.
53. Grivel JC, Penn ML, Eckstein DA, Schramm B, Speck RF, Abbey NW, et al. Human immunodeficiency virus type 1 coreceptor preferences determine target T-cell depletion and cellular tropism in human lymphoid tissue. J Virol 2000, 74:5347-5351.
54. Grivel JC, Margolis LB. CCR5- and CXCR4-tropic HIV-1 are equally cytopathic for their T-cell targets in human lymphoid tissue [see comments]. Nat Med 1999, 5:344-346.
55. Berger EA, Murphy PM, Farber JM. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 1999, 17:657-700.
56. Platt EJ, Madani N, Kozak SL, Kabat D. Infectious properties of human immunodeficiency virus type 1 mutants with distinct affinities for the CD4 receptor. J Virol 1997, 71:883-890.
57. Platt EJ, Wehrly K, Kuhmann SE, Chesebro B, Kabat D. Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. J Virol 1998, 72:2855-2864.
58. Wu L, Paxton WA, Kassam N, Ruffing N, Rottman JB, Sullivan N, et al. CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J Exp Med 1997, 185:1681-1691.
59. Speck RF, Wehrly K, Platt EJ, Atchison RE, Charo IF, Kabat D, et al. Selective employment of chemokine receptors as human immuno-deficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop. J Virol 1997, 71:7136-7139.