Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase

Science. 1991 Sep 27;253(5027):1557-9. doi: 10.1126/science.1716788.


Serial human immunodeficiency virus type-1 (HIV-1) isolates were obtained from five individuals with acquired immunodeficiency syndrome (AIDS) who changed therapy to 2',3'-dideoxyinosine (ddI) after at least 12 months of treatment with 3'-azido-3'-deoxythymidine (zidovudine, AZT). The in vitro sensitivity to ddI decreased during the 12 months following ddI initiation, whereas AZT sensitivity increased. Analysis of the reverse transcriptase coding region revealed a mutation associated with reduced sensitivity to ddI. When this mutation was present in the same genome as a mutation known to confer AZT resistance, the isolates showed increased sensitivity to AZT. Analysis of HIV-1 variants confirmed that the ddI resistance mutation alone conferred ddI and 2',3'-dideoxycytidine resistance, and suppressed the effect of the AZT resistance mutation. The use of combination therapy for HIV-1 disease may prevent drug-resistant isolates from emerging.

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / microbiology
  • Base Sequence
  • DNA, Viral / genetics*
  • Didanosine / pharmacology*
  • Didanosine / therapeutic use*
  • Drug Resistance, Microbial
  • Genotype
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / isolation & purification
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Oligodeoxyribonucleotides
  • RNA-Directed DNA Polymerase / genetics*
  • RNA-Directed DNA Polymerase / metabolism
  • Zidovudine / pharmacology
  • Zidovudine / therapeutic use*


  • DNA, Viral
  • Oligodeoxyribonucleotides
  • Zidovudine
  • RNA-Directed DNA Polymerase
  • Didanosine