Case Study #4 Lamivudine (LMV) Resistance

LMV Resistance

  • 1995
    • incidental diagnosis of Chronic HBV in a 60 year old male
    • Perinatal/early childhood transmission
    • Italian-born, no other risk factors/family History
  • No physical signs of chronic liver disease
  • ALT 99 IU/L
  • HBsAg +ve
  • HBeAg -ve, anti-Hbe +ve
  • HBV DNA < 6.69 log10 IU/ml initially
  • HBV DNA- 7.39 log10 IU/ml after 18 months of observation

LMV Resistance

  1. Patient commenced LMV monotherapy
    • Effective suppression of viral replication
    • Serum ALT levels with normal range
  2. Virological breakthrough on LMV

LMV Resistance

Drug Resistance Testing

  1. Antiviral drug resistance testing was performed following virological breakthrough on LMV
    • Primary Resistance mutation rtM204I associated with LMV resistance was detected

LMV Resistance

  1. LMV therapy stopped following virological breakthrough
  2. Patient experienced a virological flare off therapy
  3. Recommenced LMV therapy
    • Initial virological response
    • HBV DNA suppressed
    • Normalisation of serum ALT
  4. HBV DNA land ALT levels rising
  5. Patient switched to ADV monotherapy
    • Effective suppression of viral replication
    • Serum ALT levels return to normal
  6. HBV DNA levels become elevated
    • LMV is added to the treatment protocol

LMV Resistance

Drug resistance Testing:

  1. Antiviral drug resistance testing was performed following virological flare off LMV
    • Wild type (WT) virus was detected
  2. Antiviral drug resistance testing Was performed following HBV DNA and serum ALT increase
    • Primary Resistance mutations rtL180M + rtM204I associated with LMV resistance was detected
  3. Antiviral drug resistance testing Was performed following HBV NA increase on combination therapy
    • Primary Resistance mutation rtM204I associated with LMV resistance was detected in addition to the primary adefovir resistance mutations rtA181A/V + rtN236T