title: Serum lamivudine levels in the presence of a lamivudine-resistant HBV mutant.
abstract: OBJECTIVE
  Lamivudine efficiently inhibits hepatitis B virus replication and has been used to treat hepatitis B virus recurrence after orthotopic liver transplantation. Although effective, its use is hampered by viral breakthrough due to the appearance of hepatitis B virus drug-resistant strains. Aims of this work were to evaluate the inter- and intra-individual variations of lamivudine serum levels and the effects on the drug levels of the lamivudine-resistant hepatitis B virus mutant infection.
  
  
  METHODS
  Serum lamivudine concentration was measured by high-performance liquid chromatography. Polymerase chain reaction analysis and sequencing analysis of the reverse transcriptase area of the polymerase was performed on each sample using specific primers. A polymerase chain reaction-enzyme-linked immunosorbent assay was used to differentiate between wild-type hepatitis B virus and lamivudine-resistant hepatitis B virus strain.
  
  
  RESULTS
  Lamivudine serum levels presented minor inter- and intra-individual fluctuations along time, with an important increase at the time of the hepatitis flare-up due to the hepatitis B virus mutant presence. When the wild-type hepatitis B virus briefly reappeared as a mixed population, the titre of lamivudine dropped to below the detection level.
  
  
  CONCLUSIONS
  While lamivudine serum levels appears stable when the anti-viral efficacy is fully achieved, important fluctuations are present according to the type of viral population, with a considerable decrease possibly due to the presence of the wild-type virus.
authors.affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Torre
authors.forename: F
authors.initials: F
authors.lastname: Mattioli
authors.forename: N
authors.initials: N
authors.lastname: Campo
authors.forename: A
authors.initials: A
authors.lastname: Delfino
authors.forename: M
authors.initials: M
authors.lastname: Basso
authors.forename: N
authors.initials: N
authors.lastname: Pelli
authors.forename: A
authors.initials: A
authors.lastname: Martelli
authors.forename: A
authors.initials: A
authors.lastname: Picciotto
mesh_terms: D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D024882:Drug Resistance, Viral / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D006509:Hepatitis B / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012008:Recurrence
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine