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Sci Rep. 2017 Nov 22;7(1):16017. doi: 10.1038/s41598-017-15987-1.

Baseline and Breakthrough Resistance Mutations in HCV Patients Failing DAAs.

Author information

1
Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
2
Institute of Infectious Diseases, University of Pavia, Pavia, Italy.
3
Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
4
Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
5
School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy.
6
Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
7
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
8
Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. f.baldanti@smatteo.pv.it.
9
Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy. f.baldanti@smatteo.pv.it.

Abstract

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.

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