Effect of tenofovir disoproxil fumarate on drug-resistant HBV clones.
J Infect
; 72(1): 91-102, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26515673
ABSTRACT
BACKGROUND & AIMS:
Tenofovir disoproxil fumarate (TDF) has been approved for chronic hepatitis B treatment, and favorable susceptibility of hepatitis B virus (HBV) has been indicated. However, differences in TDF susceptibility among HBV genotypes and drug-resistant strains are unclear. In this study, TDF susceptibilities between genotypes A and C were evaluated in vitro and in vivo using several drug-resistant HBV clones.METHODS:
HBV expression plasmids were constructed from sera of HBV carriers, and drug-resistant substitutions were introduced by site-directed mutagenesis. TDF susceptibility was evaluated by changes of core-associated HBV replication intermediates in vitro or by change of serum HBV DNA in human hepatocyte chimeric mice carrying each HBV clone in vivo.RESULTS:
TDF susceptibilities of lamivudine-resistant clones (rtL180M/M204V) and lamivudine plus entecavir-resistant clones (rtL180M/S202G/M204V) were similar to wild type clones in vitro. However, lamivudine plus adefovir-resistant clones (rtA181T/N236T) acquired tolerance to TDF, and the rtN236T mutation was considered to be a causal substitution for TDF resistance. Furthermore, genotypic differences in TDF susceptibility were also observed between genotypes A and C in vitro, and the differences could be confirmed in vivo (p = 0.023).CONCLUSIONS:
The present study indicates that TDF susceptibility varies among HBV genotypes and drug-resistant HBV clones.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Vírus da Hepatite B
/
Hepatite B Crônica
/
Farmacorresistência Viral
/
Tenofovir
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Infect
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Japão