Open Access
Nucleotide Polymerase Inhibitor So fos bu vir plus Ribavirin for Hepatitis C
E.J. Gane,Catherine A.M. Stedman,Robert H. Hyland,Xiao Ding,Evguenia S. Svarovskaia,William T. Symonds,R. Hindes,M.M. Berrey +7 more
TLDR
Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection, and the rate of sustained virologic response 24 weeks after therapy is reported.Abstract:
BACKGROUND The standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated so fos bu vir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection. METHODSread more
Citations
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Current prospects for interferon-free treatment of hepatitis C in 2012.
TL;DR: The prospect of interferon‐free combination DAA therapy for hepatitis C virus is now finally becoming a reality, with combinations of asunaprevir and daclatasvir and sofosbuvir and ribavirin.
Journal ArticleDOI
Hepatitis C drugs: The end of the pegylated interferon era and the emergence of all-oral, interferon-free antiviral regimens: A concise review
Alan Hoi Lun Yau,Eric M. Yoshida +1 more
TL;DR: The optimal all-oral interferon-free antiviral regimen likely entails a combination of an NS5B nucleotide polymerase inhibitor with either a second-generation NS3/4A protease inhibitor or an NS 5A replication complex inhibitor with or without RBV.
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Importance of HCV genotype 1 subtypes for drug resistance and response to therapy
TL;DR: Resistance to approved and investigational direct‐acting antivirals for the treatment of HCV is explored, focusing on the differences between genotypes 1a and genotype 1b, which are associated with a lower rate of resistant variant selection and better response to triple therapy compared withgenotype 1a.
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Hepatitis C virus therapy update 2013
Lisa C Casey,William M. Lee +1 more
TL;DR: The standard of care for treatment of HCV genotype 1 changed dramatically with the approval of two new DAA drugs for use in pegylated interferon-based and ribavirin-based triple therapy in mid-2011.
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Is 3 the new 1: perspectives on virology, natural history and treatment for hepatitis C genotype 3.
TL;DR: The virology, natural history and the treatment of genotype 3 hepatitis C are reviewed, which is now potentially the most difficult to treat genotype and an area of intense research for new drug development.
References
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Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance.
Dongliang Ge,Jacques Fellay,Alexander J. Thompson,Jason Simon,Kevin V. Shianna,Thomas J. Urban,Erin L. Heinzen,Ping Qiu,Arthur H. Bertelsen,Andrew J. Muir,Mark S. Sulkowski,John G. McHutchison,David Goldstein +12 more
TL;DR: It is reported that a genetic polymorphism near the IL28B gene, encoding interferon-λ-3 (IFN-α-2a) is associated with an approximately twofold change in response to treatment, both among patients of European ancestry and African-Americans.
Journal ArticleDOI
Diagnosis, management, and treatment of hepatitis C: An update
TL;DR: This document has been approved by the AASLD, the Infectious Diseases Society of America, and the American College of Gastroenterology.
Journal ArticleDOI
Discovery of a β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus.
Michael J. Sofia,Donghui Bao,Wonsuk Chang,Jinfa Du,Dhanapalan Nagarathnam,Rachakonda Suguna,P. Ganapati Reddy,Bruce S. Ross,Peiyuan Wang,Hai-Ren Zhang,Shalini Bansal,Christine Espiritu,Meg Keilman,Angela M. Lam,Holly M. Micolochick Steuer,Congrong Niu,Michael J. Otto,Phillip A. Furman +17 more
TL;DR: Phosphoramidate prodrugs of the 5'-phosphate derivative of the β-d- 2'-deoxy-2'-α-fluoro-2-β-C-methyluridine nucleoside showed significant potency in the HCV subgenomic replicon assay and produced high levels of triphosphates 6 in primary hepatocytes and in the livers of rats, dogs, and monkeys when administered in vivo.
Journal ArticleDOI
Preliminary Study of Two Antiviral Agents for Hepatitis C Genotype 1
Anna S. Lok,David F. Gardiner,Eric Lawitz,Claudia Martorell,Gregory T. Everson,Reem Ghalib,Robert Reindollar,Vinod K. Rustgi,Fiona McPhee,Megan Wind-Rotolo,Anna Persson,Kurt Zhu,Dessislava Dimitrova,Timothy Eley,Tong Guo,Dennis M. Grasela,Claudio Pasquinelli +16 more
TL;DR: This preliminary study involving patients with chronic HCV genotype 1 infection who had not had a response to prior therapy showed that a sustained virologic response can be achieved with two direct-acting antiviral agents only.
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Naturally occurring dominant resistance mutations to hepatitis c virus protease and polymerase inhibitors in treatment-naive patients
Thomas Kuntzen,Joerg Timm,Andrew Berical,Niall Lennon,Aaron M. Berlin,Sarah Young,Bongshin Lee,David Heckerman,Jonathan M. Carlson,Laura L. Reyor,Marianna Kleyman,Cory M. McMahon,Christopher E. Birch,Julian Schulze zur Wiesch,Timothy Ledlie,Michael Koehrsen,Chinnappa D. Kodira,Andrew Roberts,Georg M. Lauer,Hugo R. Rosen,Florian Bihl,Andreas Cerny,Ulrich Spengler,Zhimin Liu,Arthur Y. Kim,Yanming Xing,Arne Schneidewind,Margaret A. Madey,Jaquelyn Fleckenstein,Vicki M. Park,James E. Galagan,Chad Nusbaum,Bruce D. Walker,Bruce D. Walker,Gerond Lake-Bakaar,Eric S. Daar,Ira M. Jacobson,Edward D. Gomperts,Brian R. Edlin,Sharyne M. Donfield,Raymond T. Chung,Andrew H. Talal,Tony N. Marion,Bruce W. Birren,Matthew R. Henn,Todd M. Allen +45 more
TL;DR: Naturally occurring dominant STAT‐C resistance mutations are common in treatment‐naïve patients infected with HCV genotype 1, and their influence on treatment outcome should be characterized to evaluate possible benefits of drug resistance testing for individual tailoring of drug combinations when treatment options are limited due to previous nonresponse to peginterferon and ribavirin.