Emergence of resistance-associated variants after failed triple therapy with vaniprevir in treatment-experienced non-cirrhotic patients with hepatitis C-genotype 1 infection: a population and clonal analysis.
Virology
; 443(2): 278-84, 2013 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-23763767
ABSTRACT
BACKGROUND:
Vaniprevir with P/R improved SVR rates over P/R alone in treatment-experienced patients with chronic HCV-genotype 1 infection, but treatment failure presents therapeutic challenges. We identified RAVs from non-cirrhotic patients failing to achieve SVR on vaniprevir-containing regimens from a dose/duration-ranging trial of triple-combination therapy.METHODS:
Using population analysis, resistance sequencing was performed on all baseline samples and on samples at virologic failure in the vaniprevir arms. Longitudinal clonal analyses were performed on viral isolates from six vaniprevir recipients experiencing breakthrough viremia.RESULTS:
Baseline RAVs were detected in two patients subsequently experiencing virologic failure. At virologic failure, the majority of RAVs had substitutions at R155, A156, or D168. Clonal analyses identified novel double/triple variants emerging with continuing vaniprevir dosing.CONCLUSIONS:
RAVs were predominantly observed at R155, A156, and/or D168 during virologic failure on vaniprevir/P/R. Double/triple RAVs were identified in patients remaining viremic on triple therapy, suggesting evolution of resistance under selective pressure.Palavras-chave
DAA; HCV; Hepatitis C-genotype 1; IC50; IU/mL; LLD; LLQ; P/R; Resistance-associated variants; SVR; Vaniprevir; directly acting antiviral agent; hepatitis C virus; inhibitory concentration 50%; international units per milliliter; lower limit of detection; lower limit of quantification; peginterferon alfa/ribavirin; sustained virologic response
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Peptídeo Hidrolases
/
Variação Genética
/
Hepacivirus
/
Hepatite C Crônica
/
Farmacorresistência Viral
/
Indóis
Tipo de estudo:
Clinical_trials
/
Risk_factors_studies
Idioma:
En
Revista:
Virology
Ano de publicação:
2013
Tipo de documento:
Article