[Molecular basis and clinical significance of HIV-1 resistance to nucleoside compounds]

C R Acad Sci III. 1995 Mar;318(3):315-28.
[Article in French]


The prolonged use of anti-viral nucleosides (ZDV, ddI, ddC) in HIV-infected patients has given rise to the isolation of viral variants that display resistance against these compounds. Tissue culture selection experiments, involving increasing concentrations of anti-viral compounds, have likewise been shown to select for drug-resistant strains of HIV. Cloning, sequencing and site-directed mutagenesis have shown that a series of point mutations in the viral reverse transcriptase (RT) are responsible for this phenomenon. A different series of mutations in RT are responsible for resistance against non-nucleoside inhibitors of this enzyme. These mutations are due to the error-prone nature of RT during viral replication. Mutated forms of recombinant RT, that derive from drug-resistant viruses, have reduced affinity for relevant triphosphorylated nucleosides.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Drug Resistance, Multiple
  • Genotype
  • HIV Reverse Transcriptase
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Mutation
  • Nucleosides / pharmacology*
  • RNA-Directed DNA Polymerase / genetics
  • RNA-Directed DNA Polymerase / metabolism


  • Nucleosides
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase