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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Treatment of hepatitis C with an interferon-based lead-in phase: a perspective from mathematical modelling.
TL;DR: Viral kinetics during a period of PEG-IFN/RBV therapy, combined with other factors, such as the IL28B polymorphism and baseline viral load, can identify IFN-sensitive patients and help develop response-guided therapies.
Journal ArticleDOI
Baseline dasabuvir resistance in Hepatitis C virus from the genotypes 1, 2 and 3 and modeling of the NS5B-dasabuvir complex by the in silico approach.
Dario Akaberi,Assar Bergfors,Midori Kjellin,Nader Kameli,Nader Kameli,Louise Lidemalm,Bhavya Kolli,Robert W. Shafer,Navaneethan Palanisamy,Navaneethan Palanisamy,Johan Lennerstrand +10 more
TL;DR: Dasabuvir’s binding pose with the NS5B polymerase is predicted using the in silico methods to elucidate the reasons associated with the resistance of clinically relevant RASs.
Journal ArticleDOI
IL28B testing in a rapidly changing world: Still relevant?
Lindsay Y. King,Raymond T. Chung +1 more
TL;DR: Given the lack of alternative therapies, the multiple side effects of dual therapy, and the prolonged course of treatment with overall low rates of cure, IL28B testing held promise as a prime example of applying pharmacogenomics to the planning of antiviral therapy.
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Update on the treatment of hepatitis C genotypes 2-6.
TL;DR: Although direct-acting antivirals are transforming the treatment of all hepatitis C genotypes, ongoing studies will optimize treatment duration and provide interferon-free alternatives.
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Low Rates of Sustained Virologic Response with Peginterferon Plus Ribavirin for Chronic Hepatitis C Virus Infection in HIV Infected Patients in Rio de Janeiro, Brazil
Halime Silva Barcaui,Gerson Carreiro Tavares,Silvia Beatriz May,Carlos Eduardo Brandão-Mello,Marcia Amendola Pires,Paulo Feijó Barroso +5 more
TL;DR: SVR in HCV/HIV co-infected subjects in a public health setting is similar to that observed in clinical trials, albeit very low, and a delay in therapy initiation should be considered until new therapies as direct acting antiviral drugs (DAA) become widely available and tested in coinfected subjects.
References
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Journal ArticleDOI
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.
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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.
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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.