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Drug Resistance pp 225–239Cite as

Human Immunodeficiency Virus Replication in the Presence of Antiretroviral Drugs: Analogies to Antineoplastic Drug Resistance

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Part of the book series: Cancer Treatment and Research ((CTAR,volume 87))

Abstract

Oncologists commonly care for patients with human immunodeficiency virus (HIV)-associated malignancies. In fact, the management of HIV-infected patients with Kaposi’s sarcoma, non-Hodgkin’s lymphoma, or squamous cell carcinoma of the cervix is common in many oncology practices. In addition, many hematologists care for patients with hemophilia and HIV infection, or patients with HIV-associated hematologic disorders, such as immune thrombocytopenia, antiphospholipid antibodies, chronic cytopenias, and thrombotic thrombocytopenic purpura.

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References

  1. Lewin B (1987) Genes III. New York: John Wiley.

    Google Scholar 

  2. Roberts JD, Bebenek K, Kunkel TA (1988) The accuracy of reverse transcriptase from HIV-1. Science 242:1171.

    Article  PubMed  CAS  Google Scholar 

  3. Katz RA, Skalka AM (1990) Generation of diversity in retroviruses. Ann Rev Genet 24:409.

    Article  PubMed  CAS  Google Scholar 

  4. Preston BD, Poiesz BJ, Loeb LA (1988) Fidelity of HIV-1 reverse transcriptase. Science 242:1168.

    Article  PubMed  CAS  Google Scholar 

  5. Varmus HE (1988) Retroviruses. Science 240:1427.

    CAS  Google Scholar 

  6. Hu WS, Temin HM (1990) Retroviral recombination and reverse transcription. Science 250:1227.

    Article  PubMed  CAS  Google Scholar 

  7. Cullen BR (1991) Human immunodeficiency virus as a prototypic complex retrovirus. J Virol 65:1053–1056.

    PubMed  CAS  Google Scholar 

  8. Luciw PA, Leung NJ (1992) Mechanism of retroviral replication. In JA Levy, ed. The Retroviridae, Vol. 1. New York: Plenum Press, pp 159–298.

    Chapter  Google Scholar 

  9. Temin HM (1989) Retrovirus variation and evolution. Genome 31:17.

    Article  PubMed  CAS  Google Scholar 

  10. Myers G, Pavlakis GN (1992) Evolutionary potential of complex retroviruses. In JA Levy, ed. The Retroviridae, Vol. 1. New York: Plenum Press, pp 51–104.

    Chapter  Google Scholar 

  11. Strair RK, Mellors JW (1994) Resistance of HIV-1 to antiretroviral drugs. AIDS Updates.

    Google Scholar 

  12. Mitsuya H, Weinhold KJ, Furman PA, et al. (1985) 3′-azido-3′-deoxythymidine (BWA509U): An antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy associated virus in vitro. Proc Natl Acad Sci USA 82:7096–7100.

    Article  PubMed  CAS  Google Scholar 

  13. Mitsuya H, Broder S (1986) Inhibition of the in vitro infectivity and cytopathic effect of human Tlymphotropic virus type III/lymphadenopathy associated virus (HTLV III/LAV) by 2′,3′-dideoxynucleosides. Proc Natl Acad Sci USA 83:1911–1915.

    Article  PubMed  CAS  Google Scholar 

  14. Richman DD (1992) Antiretroviral therapy: Azidothymidine and other deoxynucleoside analogues. In VT DeVita, S Hellman, SA Rosenberg, eds. AIDS: Etiology, Diagnosis, Treatment and Prevention. Philadelphia: JB Lippincott, pp 373–387.

    Google Scholar 

  15. Fischl MA, Richman DD, Grieco MH, et al. (1987) The efficacy of azidothymidine AZT in the treatment of patients with AIDS and the AIDS related complex. A double blind placebo controlled trial. N Engl J Med 317:185–191.

    Article  PubMed  CAS  Google Scholar 

  16. Ioannidis JP, Cappellen JC, Lau J, Skolnik PR, Melville B, Chalmers TC, Sacks HS (1995) Early or deferred zidovudine therapy in HIV-infected patients without an AIDS-defining illness. Ann Intern Med 122:856–866.

    PubMed  CAS  Google Scholar 

  17. Aboulker JP, Swart AM (1993) Preliminary analysis of the Concorde trial. Lancet 341:889–890.

    Article  PubMed  CAS  Google Scholar 

  18. Larder BA, Darby G, Richman DD (1989) HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 243:1731–1734.

    Article  PubMed  CAS  Google Scholar 

  19. Richman DD, Grimes JM, Lagakos SW (1990) Effect of stage of disease and drug dose on zidovudine susceptibilities of isolates of human immunodeficiency virus. J Acquir Immune Defic Syndr 3:743–746.

    PubMed  CAS  Google Scholar 

  20. Mohn H, Singh MK, Ching WTW, Ho DD (1993) Quantitation of zidovudine resistant human immunodeficiency virus type 1 in the blood of treated and untreated patients. Proc Natl Acad Sci USA 90:25–29.

    Article  Google Scholar 

  21. Larder BA, Kemp SD (1989) Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Science 246:1155–1158.

    Article  PubMed  CAS  Google Scholar 

  22. Kellam P, Boucher CA, Larder BA (1992) Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine. Proc Natl Acad Sci USA 89:1934–1938.

    Article  PubMed  CAS  Google Scholar 

  23. Dianzani F, Antonelli G, Turriziani O, Dong G, Capobianchi MR, Riva E (1992) In vitro selection of human immunodeficiency virus type 1 resistant to 3′-azido-3′-deoxythymidine. Antiviral Res 18:39–52.

    Article  PubMed  CAS  Google Scholar 

  24. Gao Q, Gu Z, Parniak MA, Li X, Wainberg MA (1992) In vitro selection of variants of human immunodeficiency virus type 1 resistant to 3′-azido-3′-deoxythymidine and 2′,3′-dideoxyinosine. J Virol 66:12–19.

    PubMed  CAS  Google Scholar 

  25. Richman DD, Guatelli JC, Grimes J, Tsiatis A, Gingeras T (1991) Detection of mutations associated with zidovudine resistance in human immunodeficiency virus by use of the polymerase chain reaction. J Infect Dis 164:1075–1081.

    Article  PubMed  CAS  Google Scholar 

  26. Boucher CAB, Tersmette M, Lange MA, et al. (1990) Zidovudine sensitivity of human immunodeficiency viruses from high-risk, symptom-free individuals during therapy. Lancet 336:585–590.

    Article  PubMed  CAS  Google Scholar 

  27. Boucher CAB, O’Sullivan E, Mulder JW, et al. (1992) Ordered appearance of zidovudine resistance mutations during treatment of 18 human immunodeficiency virus positive subjects. J Infect Dis 165:105–110.

    Article  PubMed  CAS  Google Scholar 

  28. Kohlstaedt LAW J, Friedman JM, Rice PA, Steitz TA (1992) Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256:1783–1790.

    Article  PubMed  CAS  Google Scholar 

  29. Jacobo-Molina A, Ding J, Nanni RG, et al. (1993) Structure of HIV-1 reverse transcriptase complexed with double stranded DNA at 3.0 A resolution shows bent DNA. Proc Natl Acad Sci USA 90:6320–6324.

    Article  PubMed  CAS  Google Scholar 

  30. Boyer PL, Tantillo C, Jacobo-Molina A, et al. (1993) Structural and biochemical analysis shows nucleoside analog resistance of HIV-1 RT variants involves alterations in template: primer positioning. Third Workshop on Viral Resistance, Gaithersburg, Maryland.

    Google Scholar 

  31. Richman DD and the ACTG 164/168 Study Team (1993) Nevirapine resistance during clinical trials. Second International HIV-1 Drug Resistance Workshop. Noordwijk, the Netherlands.

    Google Scholar 

  32. Saag MS, Emini EA, Laskin OL, et al. (1993) A short-term clinical evaluation of L-697,661, a nonnucleoside inhibitor of HIV-1 reverse transcriptase. N Engl J Med 329:1065–1072.

    Article  PubMed  CAS  Google Scholar 

  33. Richman D, Shih CK, Lowy I, et al. (1991) Human immunodeficiency virus type 1 mutants resistant to nonucleoside inhibitors of reverse transcriptase arise in tissue culture. Proc Natl Acad Sci USA 88:11241–11244.

    Article  PubMed  CAS  Google Scholar 

  34. Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsh P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH, Saag MS, Shaw GM (1995) Viral dynamics in HIV-1 infection. Nature 373:117.

    Article  PubMed  CAS  Google Scholar 

  35. Havlir D, Eastman S, Richman DD (1995) HIV-1 kinetics: Rates of production and clearance of viral populations in asymptomatic patients treated with nevirapine. Abstract 229. Second National Conference: Human Retroviruses and Related Infections.

    Google Scholar 

  36. Strair RK, Medina DJ, Nelson CJ, Graubert T, Mellors JW (1993) Recombinant retrviral systems for the analysis of drug-resistant HIV. Nucleic Acids Res 21:4836–4842.

    Article  PubMed  CAS  Google Scholar 

  37. Loveday C, Kaye S, Tenant-Flowers M, Semple M, Ayliffe U, Weiler IVD, Tedder RS (1995) HIV-1 RNA serum-load and resistant viral genotypes during early zidovudine therapy. Lancet 345:820–824.

    Article  PubMed  CAS  Google Scholar 

  38. Dudley MN (1995) Clinical pharmacokinetics of nuclleoside antiretroviral agents. J Infect Dis 171(Suppl 2):S99–S112.

    Article  PubMed  Google Scholar 

  39. Stretcher BN, Pesce AJ, Frame PT, Stein DS (1994) Pharmacokinetics of zidovudine phosphorylation in peripheral blood mononuclear cells from patients infected with human immunodeficiency virus. Antimicrob Agents Chemother 38:1541–1547.

    PubMed  CAS  Google Scholar 

  40. Spira AI, Ho DD (1995) Effect of different donor cells on human immunodeficiency virus replication and selection in vitro. J Virol 69:422.

    PubMed  CAS  Google Scholar 

  41. Zhang H, Bagasra O, Niikura M, Poiesz BJ, Pomerantz RJ (1994) Intravirion reverse transcripts in the peripheral blood plasma on human immunodeficiency virus type 1-infected individuals. J Virol 68:7591.

    PubMed  CAS  Google Scholar 

  42. Hostetler KY, Richman DD, Carson DA, et al. (1992) Greatly enhanced inhibition of human immunodeficiency virus type 1 replication in CEM and HT4–6C cells by 3′-deoxythymidine diphosphate dimyristoylglycerol, a lipid prodrug of 3′-deoxythymidine. Antimicrob Agents Chemother 36:2025–2029.

    PubMed  CAS  Google Scholar 

  43. Balzarini J, Cooney DA, Dalai M (1987) 2′,3′-Dideoxycytidine: Regulation of its metabolism and antiretroviral potency by natural pyrimidine nucleosides and by inhibitors of pyrimidine nuclleotide synthesis. Mol Pharmacol 32:798.

    PubMed  CAS  Google Scholar 

  44. Furman PH, Fyfe JA, St. Clair MH, et al. (1986) Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′-triphosphate with human immunodeficiency virus reverse transcriptase. Proc Natl Acad Sci USA 83:8333–8337.

    Article  Google Scholar 

  45. Gao W-Y, Shirasaka T, Johns DG, Broder S, Mitsuya H (1993) Differential phosphorylation of azidothymidine, dideoxycytidine and dideoxyinosine in resting and activated peripheral blood mononuclear cells. J Clin Invest 91:2326–2333.

    Article  PubMed  CAS  Google Scholar 

  46. Johnson MA, Ahluwalia G, Connelly MC (1988) Metabolic pathways for the activation of the antiretroviral agent 2,′,3′-dideoxyadenosine in human lymphoid cells. J Biol Chem 263:15354.

    PubMed  CAS  Google Scholar 

  47. Richman DD, Kornbluth RS, Carson DA (1987) Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages. J Exp Med 166:1144.

    Article  PubMed  CAS  Google Scholar 

  48. Perno CF, Yarchoan R, Cooney DA, et al. (1988) Inhibition of human immunodeficiency virus replication in fresh and cultured human peripheral blood monocytes/macrophages by azidothymidine and related 2′,3′-dideoxynucleosides. J Exp Med 168:1111.

    Article  PubMed  CAS  Google Scholar 

  49. Skalski V, Chang CN, Dutschman GE, Liu SH, Cheng YC (1993) Identification of a human cytosolic exonuclease: Implication in multidrug resistance. Third Workshop on Viral Resistance, Gaithersburg, Maryland.

    Google Scholar 

  50. Mukherji E, Au JLS, Mathes LE (1994) Differential antiviral activities and intracellulalr metabolism of 3′-azido-3′-deoxythymidine and 2′,3′-dideoxyinosine in human cells. Antimicrob Agents Chemother 38:1573–1579.

    PubMed  CAS  Google Scholar 

  51. Dianzani F, Antonelli G, Torriziani O, Riva E, Simeoni E, Sagnoretti C, Stroselle S, Cianfriglia M (1994) Zidovudine induces the expression of cellular resistance affecting its antiviral activity. AIDS Res Hum Retroviruses 10:1471.

    Article  PubMed  CAS  Google Scholar 

  52. Agarwal RP, Mian AM (1991) Thymidine and zidovudine metabolism in chronically zidovudineexposed cells in vitro. Biochem Pharmacol 42:905–911.

    Article  PubMed  CAS  Google Scholar 

  53. Riva E, Turriziani O, Simeoni E, Di Marco P, Bellarosa D, Romagnoli G, Cianfriglia M, Antonelli G, Dianzani F (1994) Cellular resistance induced by in vitro AZT-treatment of CEM cells. Int Conf AIDS 10:104 (abstract no. PA0297).

    Google Scholar 

  54. Wu S, Liu X, Solorzano MM, Kwock R, Avramis VI (1995) Development of Zidovudine resistance in Jurkat T cells is associated with decreased expression of the thymidine kinase gene and hypermethylation of the 5′ end of the human TK gene. J AIDS Human Retroviruses 8:1.

    CAS  Google Scholar 

  55. Nyce J, Leonard S, Canupp D, Schulz S, Wong S (1993) Epigenetic mechanisms of drug resistance: Drug induced DNA hypermethylation and drug resistance. Proc Natl Acad Sci USA 90:2960–2964.

    Article  PubMed  CAS  Google Scholar 

  56. Avramis VI, Kwock R, Solorzano MM, Gomperts E (1993) Evidence of in vitro development of drug resistance to azidothymidine in T-lymphocytic leukemia cell lines and in pediatric patients with HIV-1 infection. J Acqu Immune Defic Syndr 6:1287–1293.

    CAS  Google Scholar 

  57. Zack JA, Haislip AM, Krogstad P, Chen IS (1992) Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. J Virol 66:1717–1725.

    PubMed  CAS  Google Scholar 

  58. Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M (1992) Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science 254:423–427.

    Article  Google Scholar 

  59. Hao Z, Cooney DA, Hartman NR, Perno CF, Fridland A, DeVico AL, et al. (1988) Factors determining the activity of 2′,3′-dideoxynucleotides in suppressing HIV in vitro. Mol Pharmacol 34:431.

    PubMed  CAS  Google Scholar 

  60. Tornevik Y, Jacobsson B, Britton S, Eriksson S (1991) Intracellular metabolism of 3′-azidothymidine in isolalted human peripheral blood mononuclear cells. AIDS Res Hum Retroviruses 7:751–759.

    Article  PubMed  CAS  Google Scholar 

  61. Medina DJ, Tung PP, Lerner-Tung MB, Nelson CJ, Mellors JW, Strair RK (1995) Sanctuary growth of HIV in the presence of 3′-azido-3′-deoxythymidine. J Virol 69:1606–1611.

    PubMed  CAS  Google Scholar 

  62. Lacey SF, Reardon JE, Furfine ES, et al. (1992) Biochemical studies on the reverse transcriptase and RNase H activities from human immunodeficiency virus strains resistant to 3′-azido-3′-deoxythymidine. J Biol Chem 267:15789–15794.

    PubMed  CAS  Google Scholar 

  63. Antonelli G, Turriziano O, Cianfriglia M, Riva E, Dong G, Fattorossi A, Dianzani F (1992) Resistance of HIV-1 to AZT might also involve the cellular expression of multidrug resistance Pglycoprotein. AIDS Res Hum Retroviruses 8:1839–1844.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Roger K. Strair
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  2. Daniel J. Medina
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Editor information

Editors and Affiliations

  1. The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA

    William N. Hait M.D., Ph.D.

  2. Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA

    William N. Hait M.D., Ph.D.

  3. Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA

    William N. Hait M.D., Ph.D.

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© 1996 Kluwer Academic Publishers

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Strair, R.K., Medina, D.J. (1996). Human Immunodeficiency Virus Replication in the Presence of Antiretroviral Drugs: Analogies to Antineoplastic Drug Resistance. In: Hait, W.N. (eds) Drug Resistance. Cancer Treatment and Research, vol 87. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1267-3_9

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  • DOI: https://doi.org/10.1007/978-1-4613-1267-3_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8540-3

  • Online ISBN: 978-1-4613-1267-3

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