Journal ArticleDOI
Hepatitis C Viral Dynamics in Vivo and the Antiviral Efficacy of Interferon-α Therapy
Avidan U. Neumann,Nancy P. Lam,Harel Dahari,David R. Gretch,Thelma E. Wiley,Thomas J. Layden,Alan S. Perelson +6 more
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TLDR
Findings show that infection with hepatitis C virus is highly dynamic and that early monitoring of viral load can help guide therapy, with blocking efficacies of 81, 95, and 96% for daily doses of 5, 10, and 15 million international units, respectively.Abstract:
To better understand the dynamics of hepatitis C virus and the antiviral effect of interferon-alpha-2b (IFN), viral decline in 23 patients during therapy was analyzed with a mathematical model. The analysis indicates that the major initial effect of IFN is to block virion production or release, with blocking efficacies of 81, 95, and 96% for daily doses of 5, 10, and 15 million international units, respectively. The estimated virion half-life (t1/2) was, on average, 2.7 hours, with pretreatment production and clearance of 10(12) virions per day. The estimated infected cell death rate exhibited large interpatient variation (corresponding t1/2 = 1.7 to 70 days), was inversely correlated with baseline viral load, and was positively correlated with alanine aminotransferase levels. Fast death rates were predictive of virus being undetectable by polymerase chain reaction at 3 months. These findings show that infection with hepatitis C virus is highly dynamic and that early monitoring of viral load can help guide therapy.read more
Citations
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Journal ArticleDOI
Hepatitis C Virus Infection
Georg M. Lauer,Bruce D. Walker +1 more
TL;DR: The institution of blood-screening measures in developed countries has decreased the risk of transfusion-associated hepatitis to a negligible level, but new cases continue to occur mainly as a result of injection-drug use and, to a lesser degree, through other means of percutaneous or mucous-membrane exposure.
Journal ArticleDOI
Antiviral Actions of Interferons
TL;DR: Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs.
Journal ArticleDOI
Robust hepatitis C virus infection in vitro
Jin Zhong,Pablo Gastaminza,Guofeng Cheng,Sharookh B. Kapadia,Takanobu Kato,Dennis R. Burton,Stefan Wieland,Susan L. Uprichard,Takaji Wakita,Francis V. Chisari +9 more
TL;DR: A simple yet robust HCV cell culture infection system based on the HCV JFH-1 molecular clone and Huh-7-derived cell lines that allows the production of virus that can be efficiently propagated in tissue culture is reported.
Journal ArticleDOI
Replication of hepatitis C virus
TL;DR: The development of complete cell-culture systems should now enable the systematic dissection of the entire viral lifecycle, providing insights into the hitherto difficult-to-study early and late steps.
Journal ArticleDOI
Peginterferon alfa-2a in patients with chronic hepatitis C.
Stefan Zeuzem,S.V. Feinman,Jens Rasenack,E.J. Heathcote,M.-Y. Lai,Edward Gane,John O'Grady,J Reichen,Moisés Diago,A. Lin,Joseph Hoffman,M.J. Brunda +11 more
TL;DR: In patients with chronic hepatitis C, a regimen of peginterferon alfa-2a given once weekly is more effective than a regimen that has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified interferonAlfa- 2a.
References
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TL;DR: The bootstrap is extended to other measures of statistical accuracy such as bias and prediction error, and to complicated data structures such as time series, censored data, and regression models.
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HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time
TL;DR: A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease, providing not only a kinetic picture ofAIDS pathogenesis, but also theoretical principles to guide the development of treatment strategies.
Journal ArticleDOI
Decay characteristics of HIV-1-infected compartments during combination therapy
Alan S. Perelson,Paulina Essunger,Yunzhen Cao,Mika Vesanen,Arlene Hurley,Kalle Saksela,Martin Markowitz,David D. Ho +7 more
TL;DR: It is estimated that 2.3–3.1 years of a completely inhibitory treatment would be required to eliminate HIV-1 from these compartments, and even longer treatment may be needed because of the possible existence of undetected viral compartments or sanctuary sites.