In vivo antagonism with zidovudine plus stavudine combination therapy

Diane V. Havlir, Camlin Tierney, Gerald H. Friedland, Richard B. Pollard, Laura Smeaton, Jean Pierre Sommadossi, Fox Lawrence, Harold Kessler, Kenneth Fife, Douglas D. Richman

Research output: Contribution to journalArticle

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Abstract

Human immunodeficiency virus (HIV)-infected subjects receiving zidovudine were randomized either to add stavudine (d4T) or didanosine (ddI) to their current regimen or to switch to ddI or d4T monotherapy. After 16 weeks of therapy, the mean reduction in HIV RNA from baseline was 0.14 log10 copies/mL in patients receiving d4T or zidovudine plus d4T. In subjects receiving ddI or ddI plus zidovudine, reductions were 0.39 and 0.56 log10, respectively. CD4 cell counts remained stable or showed modest increases in all arms except the zidovudine plus d4T arm. Patients receiving zidovudine plus d4T showed progressive declines in CD4 cell counts with a median of 22 cells/mm3 below baseline by 16 weeks. Examination of intracellular levels of d4T-triphosphate in 6 subjects was consistent with previous in vitro studies demonstrating pharmacologic antagonism between zidovudine and d4T. Analysis of these data suggests that zidovudine and d4T should not be prescribed in combination and that ddI provides greater antiviral activity than d4T in zidovudine-treated patients.

Original languageEnglish
Pages (from-to)321-325
Number of pages5
JournalJournal of Infectious Diseases
Volume182
Issue number1
DOIs
StatePublished - 2000

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Stavudine
Zidovudine
Didanosine
Therapeutics
CD4 Lymphocyte Count
HIV
Antiviral Agents
RNA

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Havlir, D. V., Tierney, C., Friedland, G. H., Pollard, R. B., Smeaton, L., Sommadossi, J. P., ... Richman, D. D. (2000). In vivo antagonism with zidovudine plus stavudine combination therapy. Journal of Infectious Diseases, 182(1), 321-325. https://doi.org/10.1086/315683

In vivo antagonism with zidovudine plus stavudine combination therapy. / Havlir, Diane V.; Tierney, Camlin; Friedland, Gerald H.; Pollard, Richard B.; Smeaton, Laura; Sommadossi, Jean Pierre; Lawrence, Fox; Kessler, Harold; Fife, Kenneth; Richman, Douglas D.

In: Journal of Infectious Diseases, Vol. 182, No. 1, 2000, p. 321-325.

Research output: Contribution to journalArticle

Havlir, DV, Tierney, C, Friedland, GH, Pollard, RB, Smeaton, L, Sommadossi, JP, Lawrence, F, Kessler, H, Fife, K & Richman, DD 2000, 'In vivo antagonism with zidovudine plus stavudine combination therapy', Journal of Infectious Diseases, vol. 182, no. 1, pp. 321-325. https://doi.org/10.1086/315683
Havlir DV, Tierney C, Friedland GH, Pollard RB, Smeaton L, Sommadossi JP et al. In vivo antagonism with zidovudine plus stavudine combination therapy. Journal of Infectious Diseases. 2000;182(1):321-325. https://doi.org/10.1086/315683
Havlir, Diane V. ; Tierney, Camlin ; Friedland, Gerald H. ; Pollard, Richard B. ; Smeaton, Laura ; Sommadossi, Jean Pierre ; Lawrence, Fox ; Kessler, Harold ; Fife, Kenneth ; Richman, Douglas D. / In vivo antagonism with zidovudine plus stavudine combination therapy. In: Journal of Infectious Diseases. 2000 ; Vol. 182, No. 1. pp. 321-325.
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