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  • Title: Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naïve patients.
    Author: Hachiya A, Gatanaga H, Kodama E, Ikeuchi M, Matsuoka M, Harada S, Mitsuya H, Kimura S, Oka S.
    Journal: Virology; 2004 Oct 01; 327(2):215-24. PubMed ID: 15351209.
    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.
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