Detection of lamivudine- or adefovir-resistant hepatitis B virus mutations by a liquid array

J Virol Methods. 2011 Jul;175(1):1-6. doi: 10.1016/j.jviromet.2011.04.005. Epub 2011 Apr 13.


A novel polymerase chain reaction (PCR)-Luminex assay was developed for rapid, accurate, and high-throughput detection of the most important hepatitis B virus (HBV) variants, including those with reverse transcriptase (RT) domain L180M, M204I/V, A181T/V/S, I233V and N236T mutations associated with resistance to lamivudine (LAM) or adefovir (ADV). Using mixtures of mutant and wild-type HBV, this method was sufficiently sensitive for detecting 10(3)HBV ml(-1) and could detect minor mutants when they comprised 5% of the total viral population. Comparison of the PCR-Luminex assay with INNO-LiPA for detecting clinical LAM- or ADV-resistant chronic hepatitis B virus infection in 64 patients confirmed the following: the 2 methods were 97.9% (48 of 49) and 93.3% (14 of 15) concordant for detecting LAM- or ADV-resistance mutations, respectively. The agreement with direct sequencing was 70.3% (45 of 64). The PCR-Luminex assay or multi-analyte suspension array can detect simultaneously and efficiently minor populations HBV mutants early during infection in many clinical samples. It is a simple, cost-effective method for resistance surveillance or selecting appropriate antiviral agents and initiating timely rescue treatment before the development drug-resistance related virus or biochemical breakthrough.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / pharmacology
  • Child
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Drug Resistance, Viral / genetics*
  • Female
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / isolation & purification*
  • Humans
  • Lamivudine / pharmacology*
  • Luminescent Measurements
  • Male
  • Middle Aged
  • Mutagenesis, Site-Directed
  • Mutation*
  • Organophosphonates / pharmacology*
  • Polymerase Chain Reaction / methods*
  • Protein Array Analysis
  • RNA-Directed DNA Polymerase / genetics
  • Reverse Transcriptase Inhibitors / pharmacology


  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • adefovir
  • RNA-Directed DNA Polymerase
  • Adenine