Evolution of primary and compensatory lamivudine resistance mutations in chronic hepatitis B virus-infected patients during long-term lamivudine treatment, assessed by a line probe assay.
J Clin Microbiol
; 45(12): 3935-41, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17913933
ABSTRACT
With the availability of more potent nucleotide/nucleoside analogues, the early detection of drug-resistant mutants of hepatitis B virus (HBV) is important for the strategic treatment of chronic hepatitis B. We studied 336 serum samples from 80 patients chronically infected with HBV who were receiving lamivudine treatment for the presence of lamivudine resistance mutations at codons 80, 173, 180, and 204 of the HBV polymerase. The sequencing data were compared with the results generated with the INNO-LiPA HBV DR (drug resistance) v2 strip, a line probe assay (LiPA) covering wild-type and mutant motifs, for resistance mutations to lamivudine and adefovir dipivoxil. This method provided at least the same information as sequencing for 99.1% of all codons analyzed. On the basis of the LiPA results, 20 of 80 patients developed a lamivudine resistance mutation after 1 year. In all 20 patients, the mutation occurred in the YMDD motif at reverse transcriptase position 204 (rt204; M204V/I) either with or without the compensatory mutation at position rt180 (L180M). A compensatory mutation at position rt80 (L80V/I) was detected in half of these patients. After 36 months, a compensatory mutation was seen at position rt173 (V173L) in 3/15 patients. Time-to-event survival analysis indicated a 2.8 times greater chance for LiPA to detect a given mutation than sequencing at any moment in time (hazard ratio, 2.8, 95% confidence interval, 1.79, 4.41; P < 0.0001). These results demonstrate that a highly sensitive and specific assay such as the INNO-LiPA HBV DR v2 can precociously detect and monitor the emergence of primary and compensatory lamivudine resistance mutations in patients chronically infected with HBV and is more sensitive than sequencing.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus da Hepatite B
/
Lamivudina
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Hepatite B Crônica
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Farmacorresistência Viral
/
Hibridização de Ácido Nucleico
Tipo de estudo:
Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article