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Stavudine (d4T, Zerit®)

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Antiviral Chemotherapy 4

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 394))

Abstract

Stavudine, 2′,3′-didehydro-3′-deoxythymidine (D4T), has recently been approved by the U.S. Food and Drug Administration for the treatment of advanced HIV-1 infection in adults who are 1) intolerant to approved therapies with proven clinical benefit, or 2) have experienced significant clinical or immunologic deterioration while receiving these therapies, or 3) for whom such therapies are contraindicated. Approval was based on studies in over 11,000 patients, almost all of whom had received prior zidovudine therapy, showing that stavudine had a beneficial effect upon surrogate markers and acceptable toxicity. The effect of stavudine in delaying progression of HIV disease awaits the completion of clinical trials which are currently in progress.

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References

  1. August EM, Birks EM, Prusoff WH. 3’-Deoxythymidin-2 ` -ene permeation of human lymphocyte H9 cells by non-facilitated diffusion. Mol. Pharmacol. 1991; 39: 246–249.

    CAS  PubMed  Google Scholar 

  2. Ho H-T., Hitchcock MJM. Cellular pharmacology of 2’, 3’–dideoxy-2’, 2’–didehydrothymidine, a nucleoside analog active against human immunodeficiency virus. Antimicrob. Agents Chemother. 1989; 33: 844–849.

    Article  CAS  PubMed  Google Scholar 

  3. Riddler SA, Anderson RE, Mellors JW. Antiretroviral Activity of Stauvudine (2’, 3’-didehydro-3’deoxythynidine, D4T) J. Antiviral Research (in press).

    Google Scholar 

  4. Lin T-S, Schinazi RF, Prusoff WH. Potent and selective in vitro activity of 3’–deoxythymidin-2’–ene (3’–deoxy-2’, 3’ -didehydrothymidine) against human immunodeficiency birus. Biochem. Pharmacol. 1987; 36: 2713–2718.

    CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Lacey SF, Larder BA. Novel mutation (V75T) in human immunodeficiency virus type 1 reverse transcriptase confers resistance to 2’, 3’–didehydro-2’, 3’–dideoxythymidine in cell culture. Antimicrob. Agents Chemother. 1994; 38: 1428–1432.

    Article  CAS  PubMed  Google Scholar 

  7. Larder BA, Chesebro B, Richman DD. Susceptibilities of zidouvudine-susceptible and -resistant human immunodeficiency virus isolates to antiviral agents determined by using a quantitative plaque reduction assay. Antimicrob. Agents Chemother 1990; 34: 436–441.

    Article  CAS  PubMed  Google Scholar 

  8. Richman DD. Susceptibility to nucleoside analogues of zidovudine-resistant isolates of human immunodeficiency virus. Am. J. Med. 1990; 99 (Suppl 5B), 8S - 10S.

    Article  Google Scholar 

  9. Mellors JW, Dutschman GE, Im GJ, Tramontano E, Winkler SR, Cheng Y-C. In vitro selection and molecular characterization of human immunodeficiency virus-1 resistant to non-nucleoside inhibitors of reverse transcriptase. Mo 1. Pharmacol. 1992; 41: 446–451.

    CAS  Google Scholar 

  10. Brankovan V, Tarantini K, Datema R, Chou TC. Strong synergistic anti-HIV activity of a purine and a pyrimidine nucleoside analog, ddI and d4T. V International Conference of AIDS, Montreal 1991; Abstract M.C.P. 128.

    Google Scholar 

  11. Sorensen AM, Nielsen C, Evaluation of the combination effect of different antiviral compounds against HIV in vitro. Scandanavian J Infect Dis 1993; 25: 365–371.

    Article  CAS  Google Scholar 

  12. Denman SL, Dunkle LM, Kaul S, McLaren C, Skowron G, Kouttab NM, Kennedy TA, Weitberg AB, Curt GA. 2’, 3’–Didehydro-3’–deoxythymidine (d4T) in patients with AIDS or AIDS-related complex: A phase I trial. J. Infect. Dis. 1993; 167: 21–29.

    Article  Google Scholar 

  13. Browne MJ, Mayer KH, Chafee SBD, Dudley MN, Graham KK, Kaul S, Geletko S, Dunkle L, Browne M, Mayer K. Pharmacokinetics of stavudine in patients with AIDS or AIDS-related complex. J. Infect. Dis. 1992; 166: 480–485.

    Article  PubMed  Google Scholar 

  14. Kim GP, Brett-Smith H, Friedland GH, Chang CP, Griffith B, Prusoff W, Cheng YC, Toxicity and Pharmacokinetics of 2’3’ didehydro 3’deoxy thymidine (D4T) at low/moderate doses, 32 1CAAC, Anaheim Calif., 1992, Abstr. no. 561.

    Google Scholar 

  15. Brett-Smith H, Griffith B, Kim G, Walesky M, Friedland G. Magintude and duration of stavudine antiretroviral effect. First National Conference of Human Retroviruses and related Infections, Washington D.C., Dec. 1993.

    Google Scholar 

  16. Dunkle L, Anderson R, McLarin C et al, Stavudine: A Promising Anti-retroviral Agent VIII International Conference on AIDS, Amsterdam, 1992, Abstr. WEB 1011.

    Google Scholar 

  17. Dunkle LM, Pavia A, Messina M, Cross A, The BMS-019 Study Group, Stavudine (d4t) vs. zidovudine (ZDV) for the treatment of HIV-infected patients wit CD4 counts of 50-S00cells/mm3 following at least 6 months zidovudine, 34th ICAAC, Orlando Fla. 1994.

    Google Scholar 

  18. Smaldone L. Personal Communication.

    Google Scholar 

  19. Lin PF, Samanta H, Rose RE, Patrick AK, et al. Genotypic and phenotypic analysis of human immunodeficiency virus type 1 isolates from patients on prolonged stavudine therapy. J Infect Dis 1994; 170: 1157–64.

    Article  CAS  PubMed  Google Scholar 

  20. Gonzalez C, Cheng YC, Griffith B, Friedland G, (unpublished).

    Google Scholar 

  21. Anderson RE, et al. Response to Stavudine (d4t) in Zidovudine naive subjects, 34th ICAAC, Orlando Fla. 1994.

    Google Scholar 

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© 1996 Springer Science+Business Media New York

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Friedland, G., Dunkle, L.W., Cross, A.P. (1996). Stavudine (d4T, Zerit®). In: Mills, J., Volberding, P.A., Corey, L. (eds) Antiviral Chemotherapy 4. Advances in Experimental Medicine and Biology, vol 394. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9209-6_24

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  • DOI: https://doi.org/10.1007/978-1-4757-9209-6_24

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9211-9

  • Online ISBN: 978-1-4757-9209-6

  • eBook Packages: Springer Book Archive

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