Inhibition of purified recombinant reverse transcriptase from wild-type and zidovudine-resistant clinical isolates of human immunodeficiency virus type 1 by zidovudine, stavudine, and lamivudine triphosphates

J Infect Dis. 2001 Nov 15;184(10):1336-40. doi: 10.1086/323995. Epub 2001 Oct 15.

Abstract

Cross-resistance between zidovudine, stavudine, and lamivudine was studied, using purified recombinant reverse transcriptase from a zidovudine-susceptible and -resistant pair of clinical isolates of human immunodeficiency virus type 1. The zidovudine-resistant isolate exhibited low-level cross-resistance to both stavudine and lamivudine in drug susceptibility assays. Enzyme from the resistant isolate demonstrated reduced inhibition by zidovudine triphosphate and stavudine triphosphate and, to a lesser extent, lamivudine triphosphate. These findings provide additional evidence at the viral and enzyme level for cross-resistance between zidovudine and stavudine, and they suggest a possible effect of zidovudine resistance on susceptibility to lamivudine.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Cytidine Triphosphate / analogs & derivatives*
  • Cytidine Triphosphate / pharmacology
  • Dideoxynucleotides
  • Dose-Response Relationship, Drug
  • Drug Resistance, Microbial
  • Escherichia coli / genetics
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Lamivudine / analogs & derivatives*
  • Lamivudine / pharmacology
  • RNA-Directed DNA Polymerase / biosynthesis
  • RNA-Directed DNA Polymerase / genetics
  • Recombinant Proteins / antagonists & inhibitors
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Stavudine / pharmacology
  • Thymine Nucleotides / pharmacology
  • Transfection
  • Zidovudine / analogs & derivatives*
  • Zidovudine / pharmacology
  • Zidovudine / therapeutic use

Substances

  • Anti-HIV Agents
  • Dideoxynucleotides
  • Recombinant Proteins
  • Reverse Transcriptase Inhibitors
  • Thymine Nucleotides
  • lamivudine triphosphate
  • Lamivudine
  • Zidovudine
  • Cytidine Triphosphate
  • zidovudine triphosphate
  • Stavudine
  • RNA-Directed DNA Polymerase