Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine.
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.
Gauthier
J
J
Department of Virology, Glaxo Wellcome, Inc., Research Triangle Park, NC 27709, USA. JG38736@glaxowellcome.com
Bourne
E J
EJ
Lutz
M W
MW
Crowther
L M
LM
Dienstag
J L
JL
Brown
N A
NA
Condreay
L D
LD
D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D014644:Genetic Variation; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014766:Viremia / Q000821:virology*
D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine