Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naïve patients

Atsuko Hachiya, Hiroyuki Gatanaga, Eiichi Kodama, Mieko Ikeuchi, Masao Matsuoka, Shigeyoshi Harada, Hiroaki Mitsuya, Satoshi Kimura, Shinichi Oka

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17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)215-224
Number of pages10
JournalVirology
Volume327
Issue number2
DOIs
Publication statusPublished - 2004 Oct 1
Externally publishedYes

Keywords

  • Drug-naïve
  • Human immunodeficiency virus type 1
  • K238S
  • Nevirapine-resistant

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Hachiya, A., Gatanaga, H., Kodama, E., Ikeuchi, M., Matsuoka, M., Harada, S., Mitsuya, H., Kimura, S., & Oka, S. (2004). Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naïve patients. Virology, 327(2), 215-224. https://doi.org/10.1016/j.virol.2004.07.001