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Chemical Compound Review

stavudine     1-[(2R,5R)-5-(hydroxymethyl)- 2,5...

Synonyms: Zerit, BMY-27857, BMY27857, BMY 27857, d4T, ...
 
 
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Disease relevance of stavudine

 

Psychiatry related information on stavudine

 

High impact information on stavudine

 

Chemical compound and disease context of stavudine

  • CONCLUSIONS: Stavudine was well tolerated and delayed progression of HIV disease in patients who had previously received 6 or more months of zidovudine treatment [2].
  • Proportions of patients with plasma HIV-1 RNA level <500 copies/ml (91% vs 42% and 60%) and <50 copies/ml (47% versus 4% and 9%) were significantly greater in the stavudine/didanosine group (P<0.001 for pairwise comparisons) [11].
  • Most of the information available on stavudine (d4T) comes from studies in patients with advanced human immunodeficiency virus (HIV) disease to whom stavudine was administered as monotherapy [12].
  • OBJECTIVE: To assess the durability of the antiretroviral effect in plasma and cerebrospinal fluid (CSF) of antiviral therapy intensification, produced by the addition of indinavir from week 12 onwards to the original regimen of zidovudine/lamivudine or stavudine/lamivudine, after 72 weeks of follow-up using an ultrasensitive HIV-1 RNA assay [13].
  • In HIV-2 isolates, the Q151M mutation alone impacts only the phenotypic susceptibility to stavudine and abacavir [14].
 

Biological context of stavudine

  • Significant phenotypic resistance to stavudine was observed only in 2 of 5 tested individuals, although IC50 values were increased only 6.6- and 9.2-fold, respectively [15].
  • It is known that stavudine is metabolized in cells to the mono-, di- and triphosphate nucleotides but the enzymes responsible for its phosphorylation are as yet unidentified [16].
  • Of the four remaining isolates, two appeared to have a multi-resistant phenotype to several nucleoside analogues and two had no detectable RT amino acid changes to account for the observed change in stavudine sensitivity [17].
  • HIV-1 reverse transcriptase (RT) genotypes were obtained from 13 patients treated with stavudine [18].
  • Diminished HIV-1 sensitivity to stavudine in patients on prolonged therapy occurs only at low levels and cannot be attributed to any single amino acid substitution in reverse transcriptase [19].
 

Anatomical context of stavudine

 

Associations of stavudine with other chemical compounds

 

Gene context of stavudine

 

Analytical, diagnostic and therapeutic context of stavudine

References

  1. Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine. Foudraine, N.A., Hoetelmans, R.M., Lange, J.M., de Wolf, F., van Benthem, B.H., Maas, J.J., Keet, I.P., Portegies, P. Lancet (1998) [Pubmed]
  2. Clinical efficacy of monotherapy with stavudine compared with zidovudine in HIV-infected, zidovudine-experienced patients. A randomized, double-blind, controlled trial. Bristol-Myers Squibb Stavudine/019 Study Group. Spruance, S.L., Pavia, A.T., Mellors, J.W., Murphy, R., Gathe, J., Stool, E., Jemsek, J.G., Dellamonica, P., Cross, A., Dunkle, L. Ann. Intern. Med. (1997) [Pubmed]
  3. Lactic acidosis and hepatic steatosis associated with use of stavudine: report of four cases. Miller, K.D., Cameron, M., Wood, L.V., Dalakas, M.C., Kovacs, J.A. Ann. Intern. Med. (2000) [Pubmed]
  4. Efficacy and tolerability of stavudine plus lamivudine in treatment-naive and treatment-experienced patients with HIV-1 infection. Katlama, C., Valantin, M.A., Matheron, S., Coutellier, A., Calvez, V., Descamps, D., Longuet, C., Bonmarchand, M., Tubiana, R., De Sa, M., Lancar, R., Agut, H., Brun-Vezinet, F., Costagliola, D. Ann. Intern. Med. (1998) [Pubmed]
  5. Fat distribution and metabolic abnormalities in HIV-infected patients on first combination antiretroviral therapy including stavudine or zidovudine: role of physical activity as a protective factor. Domingo, P., Sambeat, M.A., Pérez, A., Ordoñez, J., Rodriguez, J., Vázquez, G. Antivir. Ther. (Lond.) (2003) [Pubmed]
  6. Self-perception of body changes in persons living with HIV/AIDS: prevalence and associated factors. Santos, C.P., Felipe, Y.X., Braga, P.E., Ramos, D., Lima, R.O., Segurado, A.C. AIDS (2005) [Pubmed]
  7. Risk of HIV dementia and opportunistic brain disease in AIDS and zidovudine therapy. Baldeweg, T., Catalan, J., Gazzard, B.G. J. Neurol. Neurosurg. Psychiatr. (1998) [Pubmed]
  8. Lactic acidosis in HIV infected patients: a systematic review of published cases. Arenas-Pinto, A., Grant, A.D., Edwards, S., Weller, I.V. Sexually transmitted infections. (2003) [Pubmed]
  9. Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial. Carr, A., Workman, C., Smith, D.E., Hoy, J., Hudson, J., Doong, N., Martin, A., Amin, J., Freund, J., Law, M., Cooper, D.A. JAMA (2002) [Pubmed]
  10. Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study. Reijers, M.H., Weverling, G.J., Jurriaans, S., Wit, F.W., Weigel, H.M., Ten Kate, R.W., Mulder, J.W., Frissen, P.H., van Leeuwen, R., Reiss, P., Schuitemaker, H., de Wolf, F., Lange, J.M. Lancet (1998) [Pubmed]
  11. Results of the ALBI trial: a randomized comparison of stavudine/didanosine, zidovudine/lamivudine and alternating treatment in antiretroviral-naive patients. Molina, J.M., Chêuc, G., Ferchal, F., Journot, V., Pellegrin, I., Sombardier, M.N., Rancinan, C., Cotte, L., Madelaine, I., Debord, T., Decazes, J.M. Antivir. Ther. (Lond.) (1999) [Pubmed]
  12. Short-term efficacy and safety of stavudine in pretreated HIV-infected patients. Villalba, N., Soriano, V., Gómez-Cano, M., Castilla, J., Mas, A., González-Lahoz, J. Antivir. Ther. (Lond.) (1997) [Pubmed]
  13. Durable HIV-1 suppression with indinavir after failing lamivudine-containing double nucleoside therapy: a randomized controlled trial. Foudraine, N.A., Jurriaans, S., Weverling, G.J., Burger, D.M., Hoetelmans, R.M., Roos, M.T., Maas, J., Miedema, F., Reiss, P., Portegies, P., de Wolf, F., Lange, J.M. Antivir. Ther. (Lond.) (2001) [Pubmed]
  14. Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. Damond, F., Collin, G., Matheron, S., Peytavin, G., Campa, P., Delarue, S., Taieb, A., Bénard, A., Chêne, G., Brun-Vézinet, F., Descamps, D. Antivir. Ther. (Lond.) (2005) [Pubmed]
  15. Genotypic and phenotypic resistance to stavudine after long-term monotherapy. BMS-020 Spanish Study Group. Holguín, A., Dietrich, U., Immelmann, A., Soriano, V. Antivir. Ther. (Lond.) (1998) [Pubmed]
  16. Anti-HIV antiviral activity of stavudine in a thymidine kinase-deficient cellular line. Turriziani, O., Simeoni, E., Dianzani, F., Antonelli, G. Antivir. Ther. (Lond.) (1998) [Pubmed]
  17. Stavudine resistance: an update on susceptibility following prolonged therapy. Lin, P.F., González, C.J., Griffith, B., Friedland, G., Calvez, V., Ferchal, F., Schinazi, R.F., Shepp, D.H., Ashraf, A.B., Wainberg, M.A., Soriano, V., Mellors, J.W., Colonno, R.J. Antivir. Ther. (Lond.) (1999) [Pubmed]
  18. HIV-1 reverse transcriptase mutations found in a drug-experienced patient confer reduced susceptibility to multiple nucleoside reverse transcriptase inhibitors. Fitzgibbon, J.E., DiCola, B., Arnold, E., Das, K., Sha, B.E., Pottage, J.C., Nahass, R., Gaur, S., John, J.F. Antivir. Ther. (Lond.) (2001) [Pubmed]
  19. Diminished HIV-1 sensitivity to stavudine in patients on prolonged therapy occurs only at low levels and cannot be attributed to any single amino acid substitution in reverse transcriptase. Salomon, H., Montaner, J.S., Belmonte, A., Wainberg, M.A. Antivir. Ther. (Lond.) (1998) [Pubmed]
  20. Contribution of nucleoside-analogue reverse transcriptase inhibitor therapy to lipoatrophy from the population to the cellular level. Nolan, D., Hammond, E., James, I., McKinnon, E., Mallal, S. Antivir. Ther. (Lond.) (2003) [Pubmed]
  21. Selection of a T-cell line resistant to stavudine and zidovudine by prolonged treatment with stavudine. Turriziani, O., Scognolari, C., Bambacioni, F., Bellomi, F., Focher, F., Gentile, M., Antonelli, G. Antivir. Ther. (Lond.) (2002) [Pubmed]
  22. Antiretroviral drugs with adverse effects on adipocyte lipid metabolism and survival alter the expression and secretion of proinflammatory cytokines and adiponectin in vitro. Lagathu, C., Bastard, J.P., Auclair, M., Maachi, M., Kornprobst, M., Capeau, J., Caron, M. Antivir. Ther. (Lond.) (2004) [Pubmed]
  23. K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. Røge, B.T., Katzenstein, T.L., Obel, N., Nielsen, H., Kirk, O., Pedersen, C., Mathiesen, L., Lundgren, J., Gerstoft, J. Antivir. Ther. (Lond.) (2003) [Pubmed]
  24. Efficacy and safety of indinavir/ritonavir 400/100 mg twice daily plus two nucleoside analogues in treatment-naive HIV-1-infected patients with CD4+ T-cell counts <200 cells/mm3: 96-week outcomes. Mootsikapun, P., Chetchotisakd, P., Anunnatsiri, S., Boonyaprawit, P. Antivir. Ther. (Lond.) (2005) [Pubmed]
  25. Asymptomatic hyperlactataemia: predictive value, natural history and correlates. McComsey, G.A., Yau, L. Antivir. Ther. (Lond.) (2004) [Pubmed]
  26. Effects of zidovudine, stavudine and beta-aminoisobutyric acid on lipid homeostasis in mice: possible role in human fat wasting. Maisonneuve, C., Igoudjil, A., Begriche, K., Lettéron, P., Guimont, M.C., Bastin, J., Laigneau, J.P., Pessayre, D., Fromenty, B. Antivir. Ther. (Lond.) (2004) [Pubmed]
  27. Altered adipokine response in murine 3T3-F442A adipocytes treated with protease inhibitors and nucleoside reverse transcriptase inhibitors. Jones, S.P., Janneh, O., Back, D.J., Pirmohamed, M. Antivir. Ther. (Lond.) (2005) [Pubmed]
  28. Pyrimidine nucleoside depletion sensitizes to the mitochondrial hepatotoxicity of the reverse transcriptase inhibitor stavudine. Setzer, B., Lebrecht, D., Walker, U.A. Am. J. Pathol. (2008) [Pubmed]
  29. Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Pace, C.S., Martin, A.M., Hammond, E.L., Mamotte, C.D., Nolan, D.A., Mallal, S.A. Antivir. Ther. (Lond.) (2003) [Pubmed]
  30. The HIV-1 nucleoside reverse transcriptase inhibitors stavudine and zidovudine alter adipocyte functions in vitro. Caron, M., Auclair, M., Lagathu, C., Lombès, A., Walker, U.A., Kornprobst, M., Capeau, J. AIDS (2004) [Pubmed]
  31. Effect of the combination of interferon-alpha and stavudine on Friend virus infections in (B10.A x A.By)F1 mice. Sidwell, R.W., Warren, R.P., Okleberry, K., Burger, R.A., Morrey, J.D. J. Infect. Dis. (1995) [Pubmed]
  32. Low plasma level of adiponectin is associated with stavudine treatment and lipodystrophy in HIV-infected patients. Lindegaard, B., Keller, P., Bruunsgaard, H., Gerstoft, J., Pedersen, B.K. Clin. Exp. Immunol. (2004) [Pubmed]
  33. Antiretroviral activity of stavudine (2',3'-didehydro-3'-deoxythymidine, D4T). Riddler, S.A., Anderson, R.E., Mellors, J.W. Antiviral Res. (1995) [Pubmed]
  34. Body fat changes among antiretroviral-naive patients on PI- and NNRTI-based HAART in the Swiss HIV cohort study. Young, J., Rickenbach, M., Weber, R., Furrer, H., Bernasconi, E., Hirschel, B., Tarr, P.E., Vernazza, P., Battegay, M., Bucher, H.C. Antivir. Ther. (Lond.) (2005) [Pubmed]
  35. Didanosine plus stavudine with or without hydroxyurea in HIV-1-infected patients: 1 year follow-up. Swiss HIV Cohort Study. Rutschmann, O.T., Opravil, M., Iten, A., Malinverni, R., Vernazza, P.L., Bucher, H., Bernasconi, E., Perrin, L.H., Yerly, S., Hirschel, B. Antivir. Ther. (Lond.) (1998) [Pubmed]
 
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