A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.

We propose an integrative, mechanistic model that integrates in vitro virology data, pharmacokinetics, and viral response to a combination regimen of a direct-acting antiviral (telaprevir, an HCV NS3-4A protease inhibitor) and peginterferon alfa-2a/ribavirin (PR) in patients with genotype 1 chronic...

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Autores principales:	Bambang S Adiwijaya, Tara L Kieffer, Joshua Henshaw, Karen Eisenhauer, Holly Kimko, John J Alam, Robert S Kauffman, Varun Garg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1ebc60fb8b8d4ddcaf1eafea5ed2727d
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spelling	oai:doaj.org-article:1ebc60fb8b8d4ddcaf1eafea5ed2727d2021-11-18T05:51:39ZA viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.1553-734X1553-735810.1371/journal.pcbi.1002339https://doaj.org/article/1ebc60fb8b8d4ddcaf1eafea5ed2727d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22241977/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358We propose an integrative, mechanistic model that integrates in vitro virology data, pharmacokinetics, and viral response to a combination regimen of a direct-acting antiviral (telaprevir, an HCV NS3-4A protease inhibitor) and peginterferon alfa-2a/ribavirin (PR) in patients with genotype 1 chronic hepatitis C (CHC). This model, which was parameterized with on-treatment data from early phase clinical studies in treatment-naïve patients, prospectively predicted sustained virologic response (SVR) rates that were comparable to observed rates in subsequent clinical trials of regimens with different treatment durations in treatment-naïve and treatment-experienced populations. The model explains the clinically-observed responses, taking into account the IC50, fitness, and prevalence prior to treatment of viral resistant variants and patient diversity in treatment responses, which result in different eradication times of each variant. The proposed model provides a framework to optimize treatment strategies and to integrate multifaceted mechanistic information and give insight into novel CHC treatments that include direct-acting antiviral agents.Bambang S AdiwijayaTara L KiefferJoshua HenshawKaren EisenhauerHolly KimkoJohn J AlamRobert S KauffmanVarun GargPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 1, p e1002339 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Bambang S Adiwijaya Tara L Kieffer Joshua Henshaw Karen Eisenhauer Holly Kimko John J Alam Robert S Kauffman Varun Garg A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.
description	We propose an integrative, mechanistic model that integrates in vitro virology data, pharmacokinetics, and viral response to a combination regimen of a direct-acting antiviral (telaprevir, an HCV NS3-4A protease inhibitor) and peginterferon alfa-2a/ribavirin (PR) in patients with genotype 1 chronic hepatitis C (CHC). This model, which was parameterized with on-treatment data from early phase clinical studies in treatment-naïve patients, prospectively predicted sustained virologic response (SVR) rates that were comparable to observed rates in subsequent clinical trials of regimens with different treatment durations in treatment-naïve and treatment-experienced populations. The model explains the clinically-observed responses, taking into account the IC50, fitness, and prevalence prior to treatment of viral resistant variants and patient diversity in treatment responses, which result in different eradication times of each variant. The proposed model provides a framework to optimize treatment strategies and to integrate multifaceted mechanistic information and give insight into novel CHC treatments that include direct-acting antiviral agents.
format	article
author	Bambang S Adiwijaya Tara L Kieffer Joshua Henshaw Karen Eisenhauer Holly Kimko John J Alam Robert S Kauffman Varun Garg
author_facet	Bambang S Adiwijaya Tara L Kieffer Joshua Henshaw Karen Eisenhauer Holly Kimko John J Alam Robert S Kauffman Varun Garg
author_sort	Bambang S Adiwijaya
title	A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.
title_short	A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.
title_full	A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.
title_fullStr	A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.
title_full_unstemmed	A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.
title_sort	viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis c infection.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1ebc60fb8b8d4ddcaf1eafea5ed2727d
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A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.

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