Rapid emergence of a viral resistant mutant in WHV chronically infected woodchucks treated with lamivudine and a pre-S/S CHO-derived hepatitis B virus vaccine.
To determine whether the addition of a pre-S/S human vaccine increases the antiviral activity of lamivudine, four woodchucks were treated with a daily dose of 100 mg/kg lamivudine and four 50 microg doses of CHO-derived pre-S/S human vaccine. WHV DNA titres decreased up to two logarithms in three woodchucks. At week 4, in three of the animals, the sequence analysis showed a predominant strain containing a nucleotide change from A to T at position 1696 of domain B of the WHV DNA polymerase. Vaccination did not further suppress WHV DNA, despite anti-HBs production in three animals. The woodchuck remains a useful model for characterising the biology and kinetics of the emergence of drug-resistant variants and could be used for pre-clinical studies of combinations of new antiviral drugs.
D'Ugo
Emilio
E
Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Kondili
Loreta A
LA
Canitano
Andrea
A
Catone
Stefania
S
Giuseppetti
Roberto
R
Gallinella
Bruno
B
Palmieri
Giampiero
G
Orobello
Sara
S
Argentini
Claudio
C
Glück
Reinhard
R
Rapicetta
Maria
M
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004279:DNA, Viral / Q000737:chemistry; D024882:Drug Resistance, Viral; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D017325:Hepatitis B Vaccines / Q000235:genetics* / Q000627:therapeutic use*; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics* / Q000276:immunology*; D007249:Inflammation / Q000473:pathology / Q000821:virology; D007700:Kinetics; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology / Q000821:virology; D008392:Marmota / Q000821:virology*; D009000:Monocytes / Q000276:immunology / Q000821:virology; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014611:Vaccination
D004279:DNA, Viral; D017325:Hepatitis B Vaccines; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine