title: Frequent detection of hepatitis B virus variants associated with lamivudine resistance in treated South African patients infected chronically with different HBV genotypes.
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.
authors.affiliation: HIV and Hepatitis Research Unit, Department of Virology, University of Limpopo, Medunsa Campus, Pretoria, South Africa. sgselabe@medunsa.ac.za
authors.forename: S Gloria
authors.initials: SG
authors.lastname: Selabe
authors.forename: Ernest
authors.initials: E
authors.lastname: Song
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Burnett
authors.forename: M Jeffrey
authors.initials: MJ
authors.lastname: Mphahlele
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology*; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013019:South Africa; D014764:Viral Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase