Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine

J Infect Dis. 1999 Dec;180(6):1757-62. doi: 10.1086/315147.


Hepatitis B viremia and emergence of hepatitis B virus (HBV) YMDD variants with reduced susceptibility to lamivudine were analyzed in patient sera from a phase II study of extended lamivudine therapy. Within 12 weeks, all patients exhibited a marked virologic response to lamivudine: >99% reduction (median 5 log decrease) in serum HBV DNA levels. Virus remained at >104 genomes/mL in 11 patients and decreased to <104 genomes/mL in the remaining 12 patients. In 10 patients, detectable YMDD variants emerged during the course of treatment. Six patients, including 3 with YMDD variants, experienced hepatitis B e antigen seroconversion while on lamivudine therapy or soon after its discontinuation. No patients with HBV DNA levels >104 genomes/mL seroconverted. Thus, patients who respond to lamivudine therapy with dramatic reductions in viral DNA level (to <104 genomes/mL) appear more likely to seroconvert than patients who do not achieve this level of HBV clearance.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • DNA, Viral / analysis
  • DNA, Viral / blood
  • Enzyme-Linked Immunosorbent Assay
  • Genetic Variation*
  • Hepatitis B Antibodies / blood
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics
  • Hepatitis B virus / isolation & purification*
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / virology*
  • Humans
  • Lamivudine / therapeutic use*
  • Polymerase Chain Reaction / methods
  • Polymorphism, Restriction Fragment Length
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Viremia / virology*


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B e Antigens
  • Reverse Transcriptase Inhibitors
  • Lamivudine