title: Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure.
abstract: K103N mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) confers high-level resistance against non-nucleoside RT inhibitors (NNRTIs) and it easily occurs partly because it arises by a single nucleotide substitution from wild-type K103. There are polymorphisms at codon 103 of HIV-1 RT. We found K103R polymorphic mutation in 3.3% of treatment-naive HIV-1-infected patients. R103N does not seem to occur as easily as K103N because R103N requires two nucleotide substitutions. To induce NNRTI resistance-associated mutations, HIV-1K103R was propagated in the presence of increasing concentrations of efavirez (EFV) or nevirapine (NVP). V179D emerged in all three EFV cultures and in two of four NVP cultures. R103G emerged by a single nucleotide substitution in one of three EFV cultures. R103N did not emerge in any of 7 NNRTI cultures. Analysis of recombinant HIV-1s showed that HIV-1K103R/V179D was significantly resistant and HIV-1K103G was moderately resistant against EFV and NVP.
authors.affiliation: AIDS Clinical Center, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. higatana@imcj.acc.go.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hachiya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D024921:Drug Resistance, Multiple, Viral; D015658:HIV Infections / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D012641:Selection, Genetic
chemical_list: D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase