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

作者：Franco S; Bellido R; Aparicio E; Canete N; Garcia Retortillo M; Sola R; Tural C; Clotet B; Paredes R; Martinez M A^*

来源：Journal of Viral Hepatitis, 2011, 18(10): E578-E582.

DOI：10.1111/j.1365-2893.2011.01490.x

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

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 naive for pegIFN alpha/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.

• 出版日期2011-10