Predominance of codon 215 mutation in reverse transcriptase-coding region of 3'-azido-3'-deoxythymidine (AZT)-resistant HIV-1 isolates after long-term AZT therapy.
Among human immunodeficiency type 1 viruses (HIV-1) isolated during long-term 3'-azido-3'-deoxythymidine (AZT) therapy, 4 condoms (Asp67, Lys70, Thr215, and Lys219) in the HIV-1-reverse transcriptase (RT)-coding region have been considered to be related to the AZT resistance of HIV-1. Therefore we determined these mutation patterns in HIV-1 isolates from patients undergoing long-term AZT treatment. In 41 clones of HIV-1 from 7 patients, the Thr215 mutation was the most predominant (97.6%), and more frequent than Asp67 (48.8%), Lys70 (31.7%) and Lys219 (9.8%) mutations. All 22 clones from isolates cultured in the presence of 1 microM AZT Thr215 mutation; such a high frequency was not found for the other 3 codon mutations. In a clinical follow-up study, Thr215 mutation appeared in the late stage of AZT treatment parallel with the emergence of AZT insusceptibility. It is worth noting that this Thr215 mutation to Tyr or Phe is a 2-nucleotide mutation in contrast to the 1-nucleotide mutations seen in the other 3 codons. Isolates with the single amino acid change of Thr215 of the RT-coding region obtained after long-term AZT treatment grew in the presence of 1 microM AZT. This single amino acid mutation in the Thr215 codon is the most important factor in AZT resistance.
Kondo
M
M
Department of Virology, Kanagawa Prefectural Public Health Laboratory, Japan.
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology*; D000596:Amino Acids / Q000235:genetics; D000998:Antiviral Agents / Q000008:administration & dosage*; D003062:Codon / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D015215:Zidovudine / Q000008:administration & dosage*
D000596:Amino Acids; D000998:Antiviral Agents; D003062:Codon; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase