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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DNA polymerase θ specializes in incorporating synthetic expanded-size (xDNA) nucleotides
Tatiana Kent,Timur Rusanov,Trung M. Hoang,Willem A. Velema,Andrew T. Krueger,William C. Copeland,Eric T. Kool,Richard T. Pomerantz +7 more
TL;DR: A unique function for Polθ is demonstrated in incorporating synthetic large-sized nucleotides into DNA large benzo-expanded nucleotide analogs which exhibit canonical base-pairing and enhanced base stacking and suggest the future possibility of the use of dxG nucleoside or related prodrug analogs as selective inhibitors of Polη activity.
Journal ArticleDOI
Management of acute and chronic HCV infection in persons with HIV coinfection.
TL;DR: The anticipated availability of safe, tolerable and highly efficacious interferon-free, oral HCV direct-acting antiviral combination therapies promise to dramatically change the management of acute and chronic HCV infection in HIV-infected persons.
Journal ArticleDOI
The Role of Chemokines in Hepatitis C Virus-Mediated Liver Disease
TL;DR: HCV-mediated changes in hepatic immune cell chemotaxis during the chronic phase of the infection are significantly affecting antiviral immunity and tissue damage and thus influence survival of both the host and the virus.
Journal ArticleDOI
Sofosbuvir-based interferon-free therapy for patients with HCV infection
TL;DR: Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infec- tion, and the rate of sustained virologic response 24 weeks after therapy is reported.
Journal ArticleDOI
Clinical Practice GuidelinesIndian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016
Pankaj Puri,Vivek A. Saraswat,Radha K. Dhiman,Anil C. Anand,Subrat K. Acharya,Shivaram Prasad Singh,Yogesh Chawla,Deepak Amarapurkar,Ajay Kumar,Anil Arora,Vinod Kumar Dixit,Abraham Koshy,Ajit Sood,Ajay Duseja,Dharmesh Kapoor,Kaushal Madan,Anshu Srivastava,Ashok Kumar,Swastik Agrawal +18 more
TL;DR: Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy.
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.
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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.
Journal ArticleDOI
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.