Viral evolutionary changes during tenofovir treatment in a chronic hepatitis B patient with sequential nucleos(t)ide therapy

J Clin Virol. 2014 Jul;60(3):313-6. doi: 10.1016/j.jcv.2014.03.018. Epub 2014 Apr 12.

Abstract

A 54-year-old man diagnosed with HBeAg-positive chronic hepatitis B (CHB) was treated with entecavir (ETV) 1mg/day following an initial unsuccessful lamivudine (LAM) treatment (rtL180M, rtM204V/I). Subsequently, virological breakthrough with ETV mutation (rtT184A/L) developed. The LAM and adefovir combination therapy was followed by virological breakthrough. The therapy had been switched to TDF monotherapy. However, this patient experienced virological breakthrough under TDF with a HBV strain bearing rtL80M, rtL180M, rtM204V/I, rtA200V, rtF221Y, rtS223A, rtT184A/L, rtR153Q, and rtV191I combined mutations without rtA194T mutation. TDF resistance may emerge due to multi-site polymerase mutations rather than single-site polymerase mutation.

Keywords: Chronic hepatitis B; Mutation; Resistance; Tenofovir.

Publication types

  • Case Reports

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Antiviral Agents / therapeutic use*
  • Drug Resistance, Viral
  • Drug Substitution
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Organophosphonates / therapeutic use*
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Tenofovir
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Tenofovir
  • Adenine