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- W2060338082 abstract "While many point mutations in the HIV-1 reversetranscriptase (RT) confer resistance to antiretroviral drugs, insertsor deletions in this gene have not been previously characterized. Inthis report, 14 RT inhibitor–treated patients were found to have HIV-1strains possessing a 6-basepair insert between codons 69 and 70 of theRT gene. Known drug resistance mutations were also observed in thesestrains, with T215Y appearing in all strains. Genotypic analysisindicated that the inserts had substantial nucleotide variability thatresulted in relatively restricted sets of amino acid sequences. Linkageof patients' treatment histories with longitudinal sequencing datashowed that insert strains appeared during drug regimens containing ddIor ddC, with prior or concurrent AZT treatment. Drug susceptibilitytests of recombinant patient isolates showed reduced susceptibility tonearly all nucleoside RT inhibitors. Site-directed mutagenesis studiesconfirmed the role of the inserts alone in conferring reducedsusceptibility to most RT inhibitors. The addition of AZT-associateddrug resistance mutations further increased the range and magnitude ofresistance. These results establish that inserts, like point mutations,are selected in vivo during antiretroviral therapy and provideresistance to multiple nucleosideanalogs." @default.
- W2060338082 created "2016-06-24" @default.
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- W2060338082 date "1999-06-16" @default.
- W2060338082 modified "2023-09-23" @default.
- W2060338082 title "A New Source of Resistance to HIV Drugs" @default.
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- W2060338082 doi "https://doi.org/10.1001/jama.281.23.2169" @default.
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