Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy

D. L. Mayers, A. J. Japour, J. M. Arduino, S. M. Hammer, R. Reichman, K. F. Wagner, R. Chung, J. Lane, C. S. Crumpacker, G. X. McLeod, Laurel A Beckett, C. R. Roberts, D. Winslow, D. Burke, N. Ruiz, M. Fujimara-Justice, P. Kernozek, J. Koch, C. Brewer

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Abstract

Human immunodeficiency virus type 1 (HIV-1) isolates resistant to zidovudine (ZDV) have previously been demonstrated to exhibit in vitro cross- resistance to other similar dideoxynucleoside agents which contain a 3'- azido group. However, cross-resistance to didanosine (ddI) or dideoxycytidine (ddC) has been less well documented. ZDV, ddI, and ddC susceptibility data have been collected from clinical HIV-1 isolates obtained by five clinical centers and their respective retrovirology laboratories. All subjects were treated only with ZDV. Clinical HIV-1 isolates were isolated, amplified, and assayed for drug susceptibility in standardized cultures of phytohemagglutinin-stimulated donor peripheral blood mononuclear cells obtained from healthy seronegative donors. All five cohorts showed a correlation between decreased in vitro susceptibility to ZDV and decreased susceptibility to ddI and ddC. For each 10-fold decrease in ZDV susceptibility, an average corresponding decrease of 2.2-fold in ddI susceptibility was observed (129 isolates studied; P < 0.001, Fisher's test of combined significance). Similarly, susceptibility to ddC decreased 2.0- fold for each 10-fold decrease in ZDV susceptibility (82 isolates studied; P < 0.001, Fisher's test of combined significance). These data indicate that a correlation exists between HIV-1 susceptibilities to ZDV and ddI or ddC for clinical HIV-1 isolates.

Original languageEnglish (US)
Pages (from-to)307-314
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume38
Issue number2
StatePublished - 1994
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Mayers, D. L., Japour, A. J., Arduino, J. M., Hammer, S. M., Reichman, R., Wagner, K. F., Chung, R., Lane, J., Crumpacker, C. S., McLeod, G. X., Beckett, L. A., Roberts, C. R., Winslow, D., Burke, D., Ruiz, N., Fujimara-Justice, M., Kernozek, P., Koch, J., & Brewer, C. (1994). Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. Antimicrobial Agents and Chemotherapy, 38(2), 307-314.