Case Study #2 Lamivudine (LMV) + Entecavir (ETV) Resistance

LMV + ETV Resistance

  • 46 year old male, anti-Hbe positive chronic HBV
  • Commenced LMV monotherapy
  • HBV DNA rebounded after 25 weeks on therapy (rtL180M+ rtM204V), continued with LMV until week 54
  • Patient commenced ETV 0.5mg daily
  • 2 log drop in HBV DNA level after 48 wks, ALT levels high 185IU/l
  • After 61 wks of ETV monotherapy LMV was recommenced

ETV Resistance

Patient previously received LMV monotherapy

  • HBV DNA levels were suppressed by two logs
  • Biochemical improvement
  • Patient experienced virological breakthrough on LMV
  • Drug resistance testing revealed the emergence of LMV resistance mutations rt V173L + rtL180M + rtM204V
  1. LMV was withdrawn following virological breakthrough and commenced ETV monotherapy
  2. The patient commenced combination ETV and LMV (3TC) therapy
    • No further improvement in serum ALT levels
    • No further suppression of viral DNA
  3. Increase in the HBV DNA viral load by of 1.5 logs

ETV Resistance

Drug Resistance Testing

  1. Primary resistance mutations associated with LMV previously detected
  2. In addition to the signature LMV resistance mutations. Two additional unique mutations rtI169T and rtM250V were detected
    • rtI169T + rtL180M + rt M204V + rtM250V together are associated with resistance to ETV
  3. Retrospective analysis has shown that these mutations could be detected by direct sequencing as early as week 68 after the start of ETV therapy
This case study highlights the need for more frequent monitoring of patients for the early emergence of drug resistance in patients