Frequent detection of hepatitis B virus variants associated with lamivudine resistance in treated South African patients infected chronically with different HBV genotypes

Authors

  • S. Gloria Selabe,

    Corresponding author
    1. HIV and Hepatitis Research Unit, Department of Virology, University of Limpopo, Medunsa Campus, Pretoria, South Africa
    • HIV and Hepatitis Research Unit, Department of Virology, P.O. Box 173, Medunsa Campus, Pretoria 0204, South Africa.
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  • Ernest Song,

    1. Hepatology Division, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa
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  • Rosemary J. Burnett,

    1. Department of Epidemiology, National School of Public Health, University of Limpopo, Medunsa Campus, Pretoria, South Africa
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  • M. Jeffrey Mphahlele

    1. HIV and Hepatitis Research Unit, Department of Virology, University of Limpopo, Medunsa Campus, Pretoria, South Africa
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Abstract

This retrospective study investigated and characterized the YMDD motif of the hepatitis B virus (HBV) reverse transcriptase (RT) gene, in sequential samples of 17 South African patients with chronic hepatitis B infection on lamivudine treatment. The profile of HBV genotypes as well as the genetic variability of pre-core (pre-C) and basal core promoter regions (BCP) were also determined in these patients. Mutations within the RT gene were determined by direct sequencing using SpectruMedix SCE 2410 genetic analyzer and INNO-LiPA HBV DR (Innogenetics), while the genetic variability of the pre-C/BCP and surface gene were determined by direct sequencing only. HBV genotypes were determined by analysis of the surface, core and RT genes using a web-based genotyping tool (NCBI). HBV DNA was quantified using Cobas Amplicor HBV Monitor assay (Roche Diagnostics). Of the 17 patients, 13 (76.5%) carried YMDD mutations: 7 with rtM204I (2 HBeAg-positive and 5 HBeAg-negative) and 6 with rtM204V (4 HBeAg-positive and 2 HBeAg-negative). Of the 13 patients with resistant HBV strains, 8 (61.5%) carried genotype A, 3 (23%) genotype B, and 2 (15.3%) genotype C. Overall, only 5 of 13 (38%) patients with YMDD mutations experienced genotypic viral drug resistance and treatment failure. Of the 17 patients, 3 carried both pre-C (G1896A) and BCP (A1762T/G1764A) mutants, 1 pre-C only and 1 BCP only. This study demonstrated frequent detection of mutations associated with lamivudine-resistance in therapy-experienced South African patients infected chronically with different HBV genotypes, and confirmed that these mutations are not always accompanied by clinical relapse. J. Med. Virol. 81:996–1001, 2009. © 2009 Wiley-Liss, Inc.

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