Treatment outcomes in hepatitis C virus genotype 1a infected patients with and without baseline NS5A resistance‐associated substitutions

2020 ◽  
Vol 40 (11) ◽  
pp. 2660-2671
Author(s):  
Julia Dietz ◽  
Johannes Vermehren ◽  
Katrin Matschenz ◽  
Peter Buggisch ◽  
Hartwig Klinker ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Treatment Outcomes ◽  
Virus Genotype ◽  
Genotype 1A

scholarly journals NS3 Variability in Hepatitis C Virus Genotype 1A Isolates from Liver Tissue and Serum Samples of Treatment-Naïve Patients with Chronic Hepatitis C

Intervirology ◽  
2018 ◽  
Vol 61 (1) ◽  
pp. 1-8
Author(s):  
Deborah D’Aliberti ◽  
Irene Cacciola ◽  
Cristina Musolino ◽  
Giuseppina Raffa ◽  
Roberto Filomia ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Liver Tissue ◽  
Serum Samples ◽  
Virus Genotype ◽  
Genotype 1A ◽  
Treatment Naïve

A large healthcare-associated outbreak of hepatitis C virus genotype 1a in a clinic in Korea

2018 ◽  
Vol 106 ◽  
pp. 53-57 ◽  
Author(s):  
Yoon-Seok Chung ◽  
Ju-yeon Choi ◽  
Myung Guk Han ◽  
Kye Ryeong Park ◽  
Su-Jin Park ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Genotype ◽  
Genotype 1A ◽  
Healthcare Associated

scholarly journals Interplay of Amino Acid Residues at Positions 28 and 31 in NS5A Defines Resistance Pathways in Hepatitis C Virus Genotype 2

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Ernest Asante-Appiah ◽  
Paul Ingravallo ◽  
Patricia McMonagle ◽  
Karin Bystol ◽  
Ellen Xia ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Treatment Outcomes ◽  
Cross Talk ◽  
Site Directed Mutagenesis ◽  
Virus Genotype ◽  
Ns5a Inhibitor ◽  
Genotype 2 ◽  
Antiviral Activities

ABSTRACT Hepatitis C virus (HCV) genotype 2 (GT2) represents approximately 9% of all viral infections globally. While treatment outcomes for GT2-infected patients have improved substantially with direct-acting antiviral agents (DAAs) compared to alpha interferon, the presence of polymorphisms in NS5A can impact the efficacy of NS5A inhibitor-containing regimens. Thus, pathways of NS5A resistance were explored in GT2 subtypes using elbasvir, an NS5A inhibitor with broad genotype activity. Resistance selection studies, resistance analysis in NS5A-inhibitor treated virologic failures, and analyses of antiviral activities in replicons bearing a panel of GT2 subtype sequences and amino acid substitutions introduced by site-directed mutagenesis were performed to define determinants of inhibitor susceptibility. Elbasvir showed differential antiviral activities in replicons bearing GT2 sequences. The 50% effective concentration (EC50) values for replicons bearing reference NS5A sequences for GT2a and GT2b were 0.003 and 3.4 nM, respectively. Studies performed with recombinant replicons demonstrated cross talk between amino acid positions 28 and 31. The combination of phenylalanine and methionine at positions 28 and 31, respectively, conferred the highest potency reduction for elbasvir in GT2a and GT2b. This combination was observed in failures seen in the C-SCAPE trial. Addition of grazoprevir, an NS3/4A protease inhibitor, to elbasvir more effectively suppressed the emergence of resistance in GT2 at modest inhibitor concentrations (3× EC90). Ruzasvir, a potent, pan-genotype NS5A inhibitor, successfully inhibited replicons bearing GT2 resistance-associated substitutions (RASs) at positions 28 and 31. The results demonstrate that cross talk between amino acids at positions 28 and 31 in NS5A modulated inhibitor potency and may impact treatment outcomes in some HCV GT2-infected patients.

scholarly journals The spread of hepatitis C virus genotype 1a in North America: a retrospective phylogenetic study

2016 ◽  
Vol 16 (6) ◽  
pp. 698-702 ◽  
Author(s):  
Jeffrey B Joy ◽  
Rosemary M McCloskey ◽  
Thuy Nguyen ◽  
Richard H Liang ◽  
Yury Khudyakov ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
North America ◽  
Phylogenetic Study ◽  
Virus Genotype ◽  
Genotype 1A

The accuracy of baseline viral load for predicting the efficacy of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1a infection: An integrated analysis

2019 ◽  
Vol 26 (3) ◽  
pp. 329-336 ◽  
Author(s):  
Lawrence Serfaty ◽  
Ira Jacobson ◽  
Jürgen Rockstroh ◽  
Frederick L. Altice ◽  
Peggy Hwang ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Baseline Viral Load ◽  
Integrated Analysis ◽  
Virus Genotype ◽  
Genotype 1A
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