Development and Validation of an Oligonucleotide Ligation Assay to Detect Lamivudine Resistance in Hepatitis B Virus

J Virol Methods. 2016 Jul;233:51-5. doi: 10.1016/j.jviromet.2016.03.014. Epub 2016 Mar 26.


Treatment of chronic hepatitis B virus (HBV) infection with lamivudine-monotherapy rapidly selects mutant variants in a high proportion of individuals. Monitoring lamivudine resistance by consensus sequencing is costly and insensitive for detection of minority variants. An oligonucleotide ligation assay (OLA) for HBV lamivudine-resistance was developed and compared to consensus sequencing. Both assays detected drug resistance mutations in 35/64 (54.7%) specimens evaluated, and OLA detected minority mutants in an additional six (9.4%). OLA may offer a sensitive and inexpensive alternative to consensus sequencing for detection of HBV drug resistance in resource-limited settings.

Keywords: HBV drug resistance; HBV treatment; Lamivudine resistance; Oligonucleotide ligation assay.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cloning, Molecular*
  • Drug Resistance, Viral*
  • Genes, Viral
  • Genotype
  • Hepatitis B / diagnosis
  • Hepatitis B / drug therapy
  • Hepatitis B / virology
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics*
  • Humans
  • Lamivudine / pharmacology*
  • Microbial Sensitivity Tests*
  • Mutation
  • Oligonucleotides


  • Antiviral Agents
  • Oligonucleotides
  • Lamivudine