title: Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naïve patients.
abstract: Several reports have recently shown that drug-resistant human immunodeficiency virus type 1 (HIV-1) is often isolated from treatment-naïve patients. We phenotypically analyzed HIV-1 strains isolated from 44 treatment-naïve individuals and found two strains highly resistant (69- and >310-fold) against nevirapine (NVP). Direct sequencing showed these two isolates had a novel mutation, K238S, in reverse transcriptase (RT), but did not have any reported NVP resistance-associated mutation. A 48-h culture in the presence of NVP, however, selected HIV-1 carrying NVP resistance-associated mutations, V106A, V108I, or both, suggesting that minor viral populations of these two isolates had harbored these mutations. Replication kinetic studies of recombinant HIV-1 clones suggested that K238S conferred a significant resistance against NVP, especially when accompanied with V106A (530-fold) or V108I (56-fold). Our study identified a novel NVP resistance-associated mutation, K238S, which could be persistently detected by genotypic assay longer than V106A and V108I during off-treatment period.
authors.affiliation: AIDS Clinical Center, International Medical Center of Japan, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hachiya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kodama
authors.forename: Mieko
authors.initials: M
authors.lastname: Ikeuchi
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Harada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology*; D010802:Phylogeny; D011995:Recombination, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase