Skip to main content
Top
Published in: Archives of Virology 11/2015

01-11-2015 | Rapid Communication

Predominance of hepatitis C virus Q80K among NS3 baseline-resistance-associated amino acid variants in direct-antiviral-agent-naïve patients with chronic hepatitis: single-centre experience

Authors: Tina Ruggiero, Alex Proietti, Lucio Boglione, Maria Grazia Milia, Tiziano Allice, Elisa Burdino, Giancarlo Orofino, Stefano Bonora, Giovanni Di Perri, Valeria Ghisetti

Published in: Archives of Virology | Issue 11/2015

Login to get access

Abstract

In the era of direct-acting antiviral agents (DAAs), hepatitis C virus (HCV) genotyping tests at baseline are controversial. The HCV NS3-Q80K polymorphism is associated with resistance to the recently approved NS3 inhibitor simeprevir (SMV) when combined with PEG-interferon and ribavirin (PEG-IFN/RBV) and alternative therapy should be considered for patients with baseline Q80K. The aim of this study was to provide an estimate of Q80K prevalence at baseline in a study group of 205 DAA-naïve patients (21 % of them with HIV coinfection) using NS3 full-population direct sequencing to detect resistance-associated amino acid variants (RAVs). NS3 RAVs were identified in 56 patients (27.3 %). Q80K was the most frequently reported one (41 %), in both HIV/HCV-coinfected and HCV-monoinfected patients, but it was only detectable in cases of HCV-subtype 1a infection. Therefore, in clinical practice, an NS3-Q80K genotyping test prior to simeprevir plus PEG-IFN/RBV treatment is highly recommended.
Literature
5.
go back to reference Bartels DJ, Zhou Y, Zhang EZ et al (2008) Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3.4A protease inhibitors in treatment-naive subjects. J Infect Dis 198:800–807. doi:10.1086/591141 CrossRefPubMed Bartels DJ, Zhou Y, Zhang EZ et al (2008) Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3.4A protease inhibitors in treatment-naive subjects. J Infect Dis 198:800–807. doi:10.​1086/​591141 CrossRefPubMed
6.
go back to reference Vicenti I, Rosi A, Saladini F et al (2012) Naturally occurring hepatitis C virus (HCV) NS3/4A protease inhibitor resistance-related mutations in HCV genotype 1-infected subjects in Italy. J Antimicrob Chemother 67:984–987. doi:10.1093/jac/dkr581 CrossRefPubMed Vicenti I, Rosi A, Saladini F et al (2012) Naturally occurring hepatitis C virus (HCV) NS3/4A protease inhibitor resistance-related mutations in HCV genotype 1-infected subjects in Italy. J Antimicrob Chemother 67:984–987. doi:10.​1093/​jac/​dkr581 CrossRefPubMed
8.
9.
go back to reference Boglione L, De Nicolò A, Cardellino CS et al (2015) Relationship between the early Boceprevir-S isomer plasma concentrations and the onset of breakthrough during HCV genotype 1 triple therapy. Clin Microbiol Infect 21(205):e1–e3. doi:10.1016/j.cmi.2014.07.009 PubMed Boglione L, De Nicolò A, Cardellino CS et al (2015) Relationship between the early Boceprevir-S isomer plasma concentrations and the onset of breakthrough during HCV genotype 1 triple therapy. Clin Microbiol Infect 21(205):e1–e3. doi:10.​1016/​j.​cmi.​2014.​07.​009 PubMed
11.
go back to reference Jacobson IM, Dore GJ, Foster GR et al (2014) Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet 384:403–413. doi:10.1016/S0140-6736(14)60494-3 CrossRefPubMed Jacobson IM, Dore GJ, Foster GR et al (2014) Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet 384:403–413. doi:10.​1016/​S0140-6736(14)60494-3 CrossRefPubMed
12.
go back to reference Manns M, Marcellin P, Poordad F et al (2014) Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 384:414–426. doi:10.1016/S0140-6736(14)60538-9 CrossRefPubMed Manns M, Marcellin P, Poordad F et al (2014) Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 384:414–426. doi:10.​1016/​S0140-6736(14)60538-9 CrossRefPubMed
14.
go back to reference Vallet S, Viron F, Henquell C et al (2011) NS3 protease polymorphism and natural resistance to protease inhibitors in French patients infected with HCV genotypes 1-5. Antiviral Ther 16:1093–1102. doi:10.3851/IMP1900 CrossRef Vallet S, Viron F, Henquell C et al (2011) NS3 protease polymorphism and natural resistance to protease inhibitors in French patients infected with HCV genotypes 1-5. Antiviral Ther 16:1093–1102. doi:10.​3851/​IMP1900 CrossRef
16.
go back to reference Nguyen LT, Gray E, Dean J, Carr M, Connell J, De Gascun C, Nguyen LA, O’Leary A, Bergin C, Hall WNS (2015) Baseline prevalence and emergence of protease inhibitor resistance mutations following treatment in chronic HCV genotype 1-infected individuals. Antiviral Ther 107:3851. doi:10.3851/IMP2964 Nguyen LT, Gray E, Dean J, Carr M, Connell J, De Gascun C, Nguyen LA, O’Leary A, Bergin C, Hall WNS (2015) Baseline prevalence and emergence of protease inhibitor resistance mutations following treatment in chronic HCV genotype 1-infected individuals. Antiviral Ther 107:3851. doi:10.​3851/​IMP2964
17.
go back to reference Manns MP, Fried MW, Zeuzem S et al (2014) Simeprevir with peginterferon/ribavirin for treatment of chronic hepatitis C virus genotype 1 infection: pooled safety analysis from Phase IIb and III studies. J Viral Hepat 22:366–375. doi:10.1111/jvh.12346 CrossRefPubMed Manns MP, Fried MW, Zeuzem S et al (2014) Simeprevir with peginterferon/ribavirin for treatment of chronic hepatitis C virus genotype 1 infection: pooled safety analysis from Phase IIb and III studies. J Viral Hepat 22:366–375. doi:10.​1111/​jvh.​12346 CrossRefPubMed
21.
go back to reference Lawitz E, Sulkowski MS, Ghalib R et al (2014) Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet 384:1756–1765. doi:10.1016/S0140-6736(14)61036-9 CrossRefPubMed Lawitz E, Sulkowski MS, Ghalib R et al (2014) Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet 384:1756–1765. doi:10.​1016/​S0140-6736(14)61036-9 CrossRefPubMed
23.
go back to reference Janssen (2013) Olysio (Simeprevir). Highlights of prescribing information. Janssen Product, LP, Titusville Janssen (2013) Olysio (Simeprevir). Highlights of prescribing information. Janssen Product, LP, Titusville
24.
25.
go back to reference HCV, DRM (HCV Phenotype Working Group). HCV Drug Development Advisory Group (2012) Clinically relevant HCV Drug resistance mutations figure and tables. Public Health 14:1–8 HCV, DRM (HCV Phenotype Working Group). HCV Drug Development Advisory Group (2012) Clinically relevant HCV Drug resistance mutations figure and tables. Public Health 14:1–8
26.
go back to reference Morsica G, Bagaglio S, Uberti-Foppa C, LA Galli L (2009) Detection of hepatitis C mutants with natural resistance to NS3/4A protease inhibitors in HIV-HCV coinfected individuals treated with antiretroviral therapy. J Acquir Immune Defic Syndr 51(106–10):104–110 Morsica G, Bagaglio S, Uberti-Foppa C, LA Galli L (2009) Detection of hepatitis C mutants with natural resistance to NS3/4A protease inhibitors in HIV-HCV coinfected individuals treated with antiretroviral therapy. J Acquir Immune Defic Syndr 51(106–10):104–110
27.
go back to reference Ogishi M, Yotsuyanagi H, Tsutsumi T et al (2015) Deconvoluting the composition of low-frequency hepatitis C viral quasispecies: comparison of genotypes and NS3 resistance-associated variants between HCV/HIV coinfected hemophiliacs and HCV monoinfected patients in Japan. PLoS ONE 10:e0119145. doi:10.1371/journal.pone.0119145 PubMedCentralCrossRefPubMed Ogishi M, Yotsuyanagi H, Tsutsumi T et al (2015) Deconvoluting the composition of low-frequency hepatitis C viral quasispecies: comparison of genotypes and NS3 resistance-associated variants between HCV/HIV coinfected hemophiliacs and HCV monoinfected patients in Japan. PLoS ONE 10:e0119145. doi:10.​1371/​journal.​pone.​0119145 PubMedCentralCrossRefPubMed
28.
go back to reference Silva T, Cortes Martins H, Coutinho R, Leitao E, Silva RPE (2015) Molecular characterization of hepatitis C virus for determination of subtypes and detection of resistance mutations to protease inhibitors in a group of intravenous drug users co-infected with HIV. J Med Virol. doi:10.1002/jmv.24213 Silva T, Cortes Martins H, Coutinho R, Leitao E, Silva RPE (2015) Molecular characterization of hepatitis C virus for determination of subtypes and detection of resistance mutations to protease inhibitors in a group of intravenous drug users co-infected with HIV. J Med Virol. doi:10.​1002/​jmv.​24213
29.
go back to reference Ehret R, Neifer S, Walter H et al (2014) Appearance of NS3 Q80K mutation in HCV genotype 1a mono- or HIV/HCV co-infected patients in a Berlin laboratory. J Int AIDS Soc 17:19741PubMedCentralPubMed Ehret R, Neifer S, Walter H et al (2014) Appearance of NS3 Q80K mutation in HCV genotype 1a mono- or HIV/HCV co-infected patients in a Berlin laboratory. J Int AIDS Soc 17:19741PubMedCentralPubMed
30.
go back to reference Halfon P, Bourliere MKH et al (2008) Mutation rate in hepatitis C virus NS3 protease is not influenced by HIV-1 protease inhibitor therapy. AIDS 22(1683–1):1683–1698 Halfon P, Bourliere MKH et al (2008) Mutation rate in hepatitis C virus NS3 protease is not influenced by HIV-1 protease inhibitor therapy. AIDS 22(1683–1):1683–1698
32.
go back to reference Kieffer TL, George S (2014) Resistance to hepatitis C virus protease inhibitors. Curr Opin Virol 8:16–21CrossRefPubMed Kieffer TL, George S (2014) Resistance to hepatitis C virus protease inhibitors. Curr Opin Virol 8:16–21CrossRefPubMed
33.
go back to reference Lenz O, Fevery K, Thys K et al (2013) Simeprevir in HCV genotype-1-infected patients: deep sequencing analyses of the PILLAR and ASPIRE Phase IIb trials. Antiviral Ther 18 suppl 1A:14 Lenz O, Fevery K, Thys K et al (2013) Simeprevir in HCV genotype-1-infected patients: deep sequencing analyses of the PILLAR and ASPIRE Phase IIb trials. Antiviral Ther 18 suppl 1A:14
Metadata
Title
Predominance of hepatitis C virus Q80K among NS3 baseline-resistance-associated amino acid variants in direct-antiviral-agent-naïve patients with chronic hepatitis: single-centre experience
Authors
Tina Ruggiero
Alex Proietti
Lucio Boglione
Maria Grazia Milia
Tiziano Allice
Elisa Burdino
Giancarlo Orofino
Stefano Bonora
Giovanni Di Perri
Valeria Ghisetti
Publication date
01-11-2015
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 11/2015
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-015-2563-3

Other articles of this Issue 11/2015

Archives of Virology 11/2015 Go to the issue