title: Genotypic evolution of HIV-1 isolates from patients after a switch of therapy from zidovudine to didanosine.
abstract: The existence of zidovudine (ZDV)-resistant and didanosine (ddI)-resistant human immunodeficiency-1 (HIV-1) variants mutated in the reverse transcriptase (RT) gene has been previously demonstrated. In this study, we tried to follow up the genotypic changes in the RT after the switch of therapy from ZDV to ddI. We studied HIV-1 isolates from 11 patients undergoing ddI therapy. Genotypic data were obtained with differential polymerase chain reaction (PCR) and with direct sequencing after PCR. The prevalence of ZDV resistance-related mutations showed a very slow decrease, particularly when patients had been treated with ZDV for a long time. The appearance of a mutation at codon 74 seemed to be independent of the presence or absence of ZDV resistance-related mutations. The broad genotypic heterogeneity of the isolates and the complexity of the evolution in one patient's isolates plead for large sequencing studies of the RT genome in new therapeutic approaches.
authors.affiliation: Laboratoire de Virologie, Université de Bordeaux II, France.
authors.forename: B
authors.initials: B
authors.lastname: Masquelier
authors.forename: I
authors.initials: I
authors.lastname: Pellegrin
authors.forename: A
authors.initials: A
authors.lastname: Ruffault
authors.forename: J M
authors.initials: JM
authors.lastname: Ragnaud
authors.forename: P
authors.initials: P
authors.lastname: Morlat
authors.forename: C
authors.initials: C
authors.lastname: Michelet
authors.forename: F
authors.initials: F
authors.lastname: Doignon
authors.forename: N
authors.initials: N
authors.lastname: Biteau
authors.forename: H J
authors.initials: HJ
authors.lastname: Fleury
mesh_terms: D001483:Base Sequence; D005075:Biological Evolution; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016049:Didanosine