title: Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase.
abstract: 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.
authors.affiliation: Division of Virology, Burroughs Wellcome Co., Research Triangle Park, NC 27709.
authors.forename: M H
authors.initials: MH
authors.lastname: St Clair
authors.forename: J L
authors.initials: JL
authors.lastname: Martin
authors.forename: G
authors.initials: G
authors.lastname: Tudor-Williams
authors.forename: M C
authors.initials: MC
authors.lastname: Bach
authors.forename: C L
authors.initials: CL
authors.lastname: Vavro
authors.forename: D M
authors.initials: DM
authors.lastname: King
authors.forename: P
authors.initials: P
authors.lastname: Kellam
authors.forename: S D
authors.initials: SD
authors.lastname: Kemp
authors.forename: B A
authors.initials: BA
authors.lastname: Larder
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000382:microbiology; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics*; D016049:Didanosine / Q000494:pharmacology* / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D005838:Genotype; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D012194:RNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D015215:Zidovudine; D012194:RNA-Directed DNA Polymerase; D016049:Didanosine