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.
Journal of Viral Hepatitis 10/2011; 18(10):e578-82. · 4.09 Impact Factor