文章基本信息

标题：Baseline and Breakthrough Resistance Mutations in HCV Patients Failing DAAs
本地全文：下载
作者：Stefania Paolucci ; Marta Premoli ; Stefano Novati 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
页码：16017
DOI：10.1038/s41598-017-15987-1
语种：English
出版社：Springer Nature
摘要：Sustained virologic response rates have increased dramatically following direct acting antiviral (DAA) therapy in chronic HCV infection. However, resistance-associated substitutions (RASs) may occur either prior to DAA or following drug exposure. The aim of this study was to determine RASs in DAA treatment-failing patients and the role of RASs in failure treatment. Six hundred and twenty HCV patients were evaluated. Direct sequencing of HCV genes was performed at breakthrough in all 31 patients failing DAAs, and in 19 baseline patients. Deep sequencing analysis was performed in 15/19 baseline patients. RASs were detected at breakthrough in 17/31 patients and at baseline in 11/19 patients, although, only 8/19 patients carried RASs associated with the prescribed regimen. Deep sequencing analysis showed RASs at baseline in 10/15 treatment-failing patients. No significant difference was observed with the Sanger sequencing. Treatment failure in the 14/31 patients without RASs was associated with suboptimal treatment. In 54.8% of treatment-failing patients one of the causes of failure might be the presence of RASs. In the majority of patients with RASs, mutations were present at baseline. Direct resistance test is advocated before treatment and at breakthrough in order to optimize retreatment regimens.