Natural prevalence of HCV minority variants that are highly resistant to NS3/4A protease inhibitors

S. Franco, R. Bellido, E. Aparicio, N. Cañete, M. García-Retortillo, R. Solà, C. Tural, B. Clotet, R. Paredes, M. A. Martínez

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12 Citations (Scopus)

Abstract

Minority drug-resistant hepatitis C virus (HCV) variants may go undetected yet be clinically important. NS3/4A protease resistance substitutions V36A and A156S/T/V were selected in patients treated with protease inhibitors. The aim of this study was to investigate whether these substitutions pre-existed in HCV infected patients. An allele-specific PCR protocol that detected the NS3/4A protease resistance substitutions V36A and A156S/T/V was used to determine the prevalence of naturally occurring variants in 45 patients. All patient samples were infected with HCV of genotype 1b and were naïve for pegIFNα/ribavirin treatment. Thirty samples (67%) had at least one HCV PI-resistant variant. A156T (23, 51%) was detected more frequently than A156V (13, 29%) or A156S (1, 2%). V36A was detected in 12 samples (27%). These results demonstrate the high prevalence of minority drug-resistant NS3/4 protease resistance substitutions. Our results also demonstrate that allele-specific PCR can be used to detect minor HCV NS3 protease resistant variants in pretreatment samples and to study in detail the evolution of mutant viruses during targeted antiviral therapy. © 2011 Blackwell Publishing Ltd.
Original languageEnglish
JournalJournal of Viral Hepatitis
Volume18
Issue number10
DOIs
Publication statusPublished - 1 Oct 2011

Keywords

  • allele-specific PCR
  • hepatitis C virus
  • minor variants
  • NS3/4A protease
  • resistance

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