scholarly journals Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C

2014 ◽  
Vol 20 (2) ◽  
pp. 199-208 ◽  
Author(s):  
Tanya L Applegate ◽  
Silvana Gaudieri ◽  
Anne Plauzolles ◽  
Abha Chopra ◽  
Jason Grebely ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hepatitis C ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Naturally Occurring

scholarly journals Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C

2016 ◽  
Vol 50 ◽  
pp. 1-5 ◽  
Author(s):  
Elif Sargin Altunok ◽  
Murat Sayan ◽  
Sila Akhan ◽  
Bilgehan Aygen ◽  
Orhan Yildiz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Chronic Hepatitis C ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Turkish Patients

scholarly journals Detection of drug resistance mutations of hepatitis C virus in patients with failure of the treatment with direct acting antivirals

2021 ◽  
Vol 98 (1) ◽  
pp. 18-27
Author(s):  
D. E. Valutite ◽  
A. V. Semenov ◽  
Yu. V. Ostankova ◽  
K. V. Kozlov ◽  
A. G. Borisov ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Treatment Failure ◽  
Chronic Hepatitis C ◽  
Direct Acting Antivirals ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Direct Acting

Background. The development of direct acting antivirals (DAAs) has spurred a revolution in treatment of patients with chronic hepatitis C. However, there are cases showing no response to treatment. In 5% of cases, the viral breakthrough is most likely caused by DAA resistance mutations in the hepatitis C virus genome.The purpose of the study is to detect drug resistance mutations of hepatitis C virus in patients with DAA treatment failure.Materials and methods. The study was performed on plasma samples from 3 patients diagnosed with chronic hepatitis C virus infection and demonstrating DAA virological treatment failure. All isolates had genotype 1b. Drug resistance mutations were detected by using direct sequencing of NS3, NS5A, and NS5B genome regions. The detection technique was developed at the Pasteur Research Institute of Epidemiology and Microbiology.Results. Drug resistance mutations were detected in all cases. By using the Geno2pheno [hcv] 0.92 tool, nucleotide substitutions were detected in different viral genome regions and presumably caused resistance or decreased sensitivity to antivirals both present and absent in the sofosbuvir + daclatasvir combination therapy. Antiviral treatment failure in patients with chronic hepatitis C is caused by drug resistance mutations.Conclusions. The developed technique is efficient for detection of drug resistance mutations in NS3, NS5A, and NS5B regions in cases of virological failure of DAA treatment.

scholarly journals Development and Validation of Two Screening Assays for the Hepatitis C Virus NS3 Q80K Polymorphism Associated with Reduced Response to Combination Treatment Regimens Containing Simeprevir

2015 ◽  
Vol 53 (9) ◽  
pp. 2942-2950 ◽  
Author(s):  
C. K. S. Chui ◽  
W. W. Y. Dong ◽  
J. B. Joy ◽  
A. F. Y. Poon ◽  
W. Y. Dong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nonstructural Protein ◽  
Automated Analysis ◽  
Pegylated Interferon ◽  
Hcv Rna ◽  
Systematic Bias ◽  
Resistance Mutations ◽  
Drug Resistance Mutations

Persons with hepatitis C virus (HCV) genotype 1a (GT1a) infections harboring a baseline Q80K polymorphism in nonstructural protein 3 (NS3) have a reduced virologic response to simeprevir in combination with pegylated interferon-alfa and ribavirin. We aimed to develop, validate, and freely disseminate an NS3 clinical sequencing assay to detect the Q80K polymorphism and potentially other HCV NS3 drug resistance mutations. HCV RNA was extracted from frozen plasma using a NucliSENS easyMAG automated nucleic acid extractor, amplified by nested reverse transcription-PCR, and sequenced using Sanger and/or next-generation (MiSeq) methods. Sanger chromatograms were analyzed using in-house software (RECall), and nucleotide mixtures were called automatically. MiSeq reads were iteratively mapped to the H77 reference genome, and consensus NS3 sequences were generated with nucleotides present at >20% called as mixtures. The accuracy, precision, and sensitivity for detecting the Q80K polymorphism were assessed in 70 samples previously sequenced by an external laboratory. A comparison of the sequences generated by the Sanger and MiSeq methods with those determined by an external lab revealed >98.5% nucleotide sequence concordance and zero discordant calls of the Q80K polymorphism. The results were both highly repeatable and reproducible (>99.7% nucleotide concordance and 100% Q80K concordance). The limits of detection (>2 and ∼5 log10IU/ml for the Sanger and MiSeq assays, respectively) are sufficiently low to allow genotyping in nearly all chronically infected treatment-naive persons. No systematic bias in the under- or overamplification of minority variants was observed. Coinfection with other viruses (e.g., HIV and hepatitis B virus [HBV]) did not affect the assay results. The two independent HCV NS3 sequencing assays with the automated analysis procedures described here are useful tools to screen for the Q80K polymorphism and other HCV protease inhibitor drug resistance mutations.

scholarly journals Next generation sequencing of the hepatitis C virus NS5B gene reveals potential novel S282 drug resistance mutations

Virology ◽  
2015 ◽  
Vol 477 ◽  
pp. 1-9 ◽  
Author(s):  
Hezhao Ji ◽  
Robert A. Kozak ◽  
Mia J. Biondi ◽  
Richard Pilon ◽  
Dominic Vallee ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Generation Sequencing
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