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

✍ Scribed by S. Gloria Selabe; Ernest Song; Rosemary J. Burnett; M. Jeffrey Mphahlele

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 83 KB
• Volume: 81
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.21479

✦ Synopsis

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.