Reverse transcriptase mutations in sequential HIV-1 isolates in a patient with AIDS.
Sequential human immunodeficiency virus type 1 (HIV-1) isolates were obtained over a 29-month period from a person before, during, and after AZT therapy. DNA sequence analysis of polymerase chain-amplified reverse-transcriptase gene showed a gradual accumulation of mutations to peak resistance (IC50 2.13 microM AZT) in association with mutations at codons 44, 210, and 369, as well as at 41, 67, 70, and 215. Eight months after cessation of AZT therapy, when an HIV-1 isolate from the patient was again sensitive to AZT, these mutations had all returned to the pretherapy sequence.
Gurusinghe
A D
AD
AIDS Molecular Biology Laboratory, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia.
Land
S A
SA
Birch
C
C
McGavin
C
C
Hooker
D J
DJ
Tachedjian
G
G
Doherty
R
R
Deacon
N J
NJ
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000821:virology*; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral; D004352:Drug Resistance, Microbial; D005260:Female; D005500:Follow-Up Studies; D005814:Genes, Viral; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D015215:Zidovudine / Q000627:therapeutic use*
D004279:DNA, Viral; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase