Linked Life Data

15302140

Source:http://linkedlifedata.com/resource/pubmed/id/15302140

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-8-10
pubmed:abstractText
Adult woodchucks (Marmota monax) chronically infected with woodchuck hepatitis virus (WHV) were treated orally with lamivudine (15 mg/kg per day) for 57 weeks. After 20 weeks of treatment a 2-3 log reduction in serum WHV DNA was detected. Serum titers of WHV then increased gradually, in the presence of lamivudine treatment, reaching pre-treatment values by week 40. Viral recrudescence was associated with development of mutations in the B domain of the WHV polymerase gene. Mutations observed in the highly conserved FLLA motif of the B domain were L564V, L565M, and A566T, with A566T being the most frequently observed. Beginning on week 57 of lamivudine treatment, one group (n = 3) was treated orally with adefovir dipivoxil at a dose of 15 mg/kg per day plus lamivudine, and a second group (n = 3) was treated with H2O placebo plus lamivudine. In woodchucks treated with adefovir dipivoxil, two had the A566T mutation, and one had both A566T and L565V. In the group maintained on lamivudine monotherapy, A566T alone was present in one animal, another carried both A566T and L565V, and in the third, no B-domain mutations were detected. There was a 4.5 log reduction in serum WHV DNA after 12 weeks of treatment with the adefovir/lamivudine combination, while in the lamivudine monotherapy controls, WHV DNA decreased by only 0.83 log (P > 0.001). A slight recurrence in serum titers of WHV DNA was observed one week after withdrawal of adefovir treatment but no further increase in viral load was observed during the remainder of the 12-week post-treatment follow-up period. The results demonstrate that supplemental adefovir dipivoxil treatment is effective in suppressing replication of lamivudine-resistant B-domain mutants in the woodchuck model of hepatitis B virus infection.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0166-3542
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
115-21
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15302140-Adenine, pubmed-meshheading:15302140-Administration, Oral, pubmed-meshheading:15302140-Amino Acid Motifs, pubmed-meshheading:15302140-Amino Acid Substitution, pubmed-meshheading:15302140-Animals, pubmed-meshheading:15302140-Antiviral Agents, pubmed-meshheading:15302140-DNA, Viral, pubmed-meshheading:15302140-DNA-Directed DNA Polymerase, pubmed-meshheading:15302140-Disease Models, Animal, pubmed-meshheading:15302140-Drug Resistance, Viral, pubmed-meshheading:15302140-Drug Therapy, Combination, pubmed-meshheading:15302140-Hepatitis B, pubmed-meshheading:15302140-Hepatitis B Virus, Woodchuck, pubmed-meshheading:15302140-Lamivudine, pubmed-meshheading:15302140-Marmota, pubmed-meshheading:15302140-Mutation, Missense, pubmed-meshheading:15302140-Phosphonic Acids, pubmed-meshheading:15302140-Protein Structure, Tertiary, pubmed-meshheading:15302140-Viremia, pubmed-meshheading:15302140-Virus Replication
pubmed:year
2004
pubmed:articleTitle
Suppression of lamivudine-resistant B-domain mutants by adefovir dipivoxil in the woodchuck hepatitis virus model.
pubmed:affiliation
Gastrointestinal Unit, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA. jrj2@cornell.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't