Modelling hepatitis C therapy—predicting effects of treatment

Perelson, Alan S.; Guedj, Jeremie

doi:10.1038/nrgastro.2015.97

Title: Modelling hepatitis C therapy—predicting effects of treatment

Journal Article · Tue Jun 30 04:00:00 UTC 2015 · Nature Reviews. Gastroenterology & Hepatology

DOI: https://doi.org/10.1038/nrgastro.2015.97 · OSTI ID:1236682

Perelson, Alan S. ^[1]; Guedj, Jeremie ^[2]

Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
INSERM, IAME, UMR, Univ. Paris Diderot, Paris (France)

Mathematically modelling changes in HCV RNA levels measured in patients who receive antiviral therapy has yielded many insights into the pathogenesis and effects of treatment on the virus. By determining how rapidly HCV is cleared when viral replication is interrupted by a therapy, one can deduce how rapidly the virus is produced in patients before treatment. This knowledge, coupled with estimates of the HCV mutation rate, enables one to estimate the frequency with which drug resistant variants arise. Modelling HCV also permits the deduction of the effectiveness of an antiviral agent at blocking HCV replication from the magnitude of the initial viral decline. One can also estimate the lifespan of an HCV-infected cell from the slope of the subsequent viral decline and determine the duration of therapy needed to cure infection. The original understanding of HCV RNA decline under interferon-based therapies obtained by modelling needed to be revised in order to interpret the HCV RNA decline kinetics seen when using direct-acting antiviral agents (DAAs). In addition, there also exist unresolved issues involving understanding therapies with combinations of DAAs, such as the presence of detectable HCV RNA at the end of therapy in patients who nonetheless have a sustained virologic response.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Los Alamos National Laboratory (LANL)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1236682

Report Number(s):: LA-UR-15-20073

Journal Information:: Nature Reviews. Gastroenterology & Hepatology, Journal Name: Nature Reviews. Gastroenterology & Hepatology Journal Issue: 8 Vol. 12; ISSN 1759-5045

Country of Publication:: United States

Language:: English

References (90)

Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics: A Randomized Clinical Trial Osinusi, Anuoluwapo; Meissner, Eric G.; Lee, Yu-Jin JAMA, Vol. 310, Issue 8 https://doi.org/10.1001/jama.2013.109309	journal	August 2013
Pharmacodynamics of PEG-IFN α differentiate HIV/HCV coinfected sustained virological responders from nonresponders Talal, Andrew H.; Ribeiro, Ruy M.; Powers, Kimberly A. Hepatology, Vol. 43, Issue 5 https://doi.org/10.1002/hep.21136	journal	May 2006
Triphasic decline of hepatitis C virus RNA during antiviral therapy Dahari, Harel; Ribeiro, Ruy M.; Perelson, Alan S. Hepatology, Vol. 46, Issue 1 https://doi.org/10.1002/hep.21657	journal	January 2007
Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients Kieffer, Tara L.; Sarrazin, Christoph; Miller, Janice S. Hepatology, Vol. 46, Issue 3 https://doi.org/10.1002/hep.21781	journal	September 2007
Ribavirin potentiates interferon action by augmenting interferon-stimulated gene induction in hepatitis C virus cell culture models Thomas, Emmanuel; Feld, Jordan J.; Li, Qisheng Hepatology, Vol. 53, Issue 1 https://doi.org/10.1002/hep.23985	journal	October 2010
Second-phase hepatitis C virus RNA decline during telaprevir-based therapy increases with drug effectiveness: Implications for treatment duration Guedj, Jeremie; Perelson, Alan S. Hepatology, Vol. 53, Issue 6 https://doi.org/10.1002/hep.24272	journal	May 2011
Hepatitis C viral kinetics with the nucleoside polymerase inhibitor mericitabine (RG7128) Guedj, Jeremie; Dahari, Harel; Shudo, Emi Hepatology, Vol. 55, Issue 4 https://doi.org/10.1002/hep.24788	journal	February 2012
Modeling viral kinetics and treatment outcome during alisporivir interferon-free treatment in hepatitis C virus genotype 2 and 3 patients: HEPATOLOGY, Vol. XX, NO. X, 2014 GUEDJ ET AL. Guedj, Jeremie; Yu, Jing; Levi, Micha Hepatology, Vol. 59, Issue 5 https://doi.org/10.1002/hep.26989	journal	April 2014
Type I interferon rapidly restricts infectious hepatitis C virus particle genesis Meredith, Luke W.; Farquhar, Michelle J.; Tarr, Alexander W. Hepatology, Vol. 60, Issue 6 https://doi.org/10.1002/hep.27333	journal	September 2014
Characterization of hepatitis C virus intergenotypic recombinant strains and associated virological response to sofosbuvir/ribavirin Hedskog, Charlotte; Doehle, Brian; Chodavarapu, Krishna Hepatology, Vol. 61, Issue 2 https://doi.org/10.1002/hep.27361	journal	December 2014
HCV Kinetic Models and Their Implications in Drug Development: HCV Kinetic Models and Their Implications Nguyen, Tht; Guedj, J. CPT: Pharmacometrics & Systems Pharmacology, Vol. 4, Issue 4 https://doi.org/10.1002/psp4.28	journal	April 2015
The metabolism, pharmacokinetics and mechanisms of antiviral activity of ribavirin against hepatitis C virus Dixit, N. M.; Perelson, A. S. Cellular and Molecular Life Sciences, Vol. 63, Issue 7-8 https://doi.org/10.1007/s00018-005-5455-y	journal	February 2006
Viral kinetic modeling: state of the art Canini, Laetitia; Perelson, Alan S. Journal of Pharmacokinetics and Pharmacodynamics, Vol. 41, Issue 5 https://doi.org/10.1007/s10928-014-9363-3	journal	June 2014
Modeling Quasispecies and Drug Resistance in Hepatitis C Patients Treated with a Protease Inhibitor Rong, Libin; Ribeiro, Ruy M.; Perelson, Alan S. Bulletin of Mathematical Biology, Vol. 74, Issue 8 https://doi.org/10.1007/s11538-012-9736-y	journal	May 2012
Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial Gane, Edward J.; Roberts, Stuart K.; Stedman, Catherine AM The Lancet, Vol. 376, Issue 9751 https://doi.org/10.1016/S0140-6736(10)61384-0	journal	October 2010
Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study Kohli, Anita; Osinusi, Anuoluwapo; Sims, Zayani The Lancet, Vol. 385, Issue 9973 https://doi.org/10.1016/S0140-6736(14)61228-9	journal	March 2015
Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial Sulkowski, Mark; Hezode, Christophe; Gerstoft, Jan The Lancet, Vol. 385, Issue 9973 https://doi.org/10.1016/S0140-6736(14)61793-1	journal	March 2015
1172 Antiviral Activity and Resistance Profile of the Novel hcv ns5a Inhibitor Gs-5885 Cheng, G.; Peng, B.; Corsa, A. Journal of Hepatology, Vol. 56 https://doi.org/10.1016/S0168-8278(12)61184-2	journal	April 2012
Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice Cento, Valeria; Tontodonati, Monica; Di Maio, Velia Chiara Digestive and Liver Disease, Vol. 47, Issue 3 https://doi.org/10.1016/j.dld.2014.12.004	journal	March 2015
Pharmacodynamics of PEG-IFN-α-2a in HIV/HCV co-infected patients: Implications for treatment outcomes Dahari, Harel; Affonso de Araujo, Evaldo S.; Haagmans, Bart L. Journal of Hepatology, Vol. 53, Issue 3 https://doi.org/10.1016/j.jhep.2010.03.019	journal	September 2010
A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1 Lawitz, Eric; Poordad, Fred; Kowdley, Kris V. Journal of Hepatology, Vol. 59, Issue 1 https://doi.org/10.1016/j.jhep.2013.02.009	journal	July 2013
Modeling hepatitis C virus dynamics: Liver regeneration and critical drug efficacy Dahari, Harel; Lo, Arthur; Ribeiro, Ruy M. Journal of Theoretical Biology, Vol. 247, Issue 2 https://doi.org/10.1016/j.jtbi.2007.03.006	journal	July 2007
Understanding hepatitis C viral dynamics with direct-acting antiviral agents due to the interplay between intracellular replication and cellular infection dynamics Guedj, J.; Neumann, A. U. Journal of Theoretical Biology, Vol. 267, Issue 3 https://doi.org/10.1016/j.jtbi.2010.08.036	journal	December 2010
Importance of very early HCV RNA kinetics for prediction of treatment outcome of highly effective all oral direct acting antiviral combination therapy Sarrazin, Christoph; Wedemeyer, Heiner; Cloherty, Gavin Journal of Virological Methods, Vol. 214 https://doi.org/10.1016/j.jviromet.2014.11.027	journal	March 2015
Mathematical analysis of multiscale models for hepatitis C virus dynamics under therapy with direct-acting antiviral agents Rong, Libin; Perelson, Alan S. Mathematical Biosciences, Vol. 245, Issue 1 https://doi.org/10.1016/j.mbs.2013.04.012	journal	September 2013
Viral dynamics in human immunodeficiency virus type 1 infection Wei, Xiping; Ghosh, Sajal K.; Taylor, Maria E. Nature, Vol. 373, Issue 6510 https://doi.org/10.1038/373117a0	journal	January 1995
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection Ho, David D.; Neumann, Avidan U.; Perelson, Alan S. Nature, Vol. 373, Issue 6510 https://doi.org/10.1038/373123a0	journal	January 1995
Decay characteristics of HIV-1-infected compartments during combination therapy Perelson, Alan S.; Essunger, Paulina; Cao, Yunzhen Nature, Vol. 387, Issue 6629 https://doi.org/10.1038/387188a0	journal	May 1997
Early and Accurate Prediction of Peg-IFNs/Ribavirin Therapy Outcome in the Individual Patient With Chronic Hepatitis C by Modeling the Dynamics of the Infected Cells Colombatto, P.; Ciccorossi, P.; Maina, Am Clinical Pharmacology & Therapeutics, Vol. 84, Issue 2 https://doi.org/10.1038/clpt.2008.21	journal	March 2008
Hepatocyte Proliferation and Hepatitis C Virus Kinetics During Treatment Dahari, H.; Rong, L.; Layden, T. J. Clinical Pharmacology & Therapeutics, Vol. 89, Issue 3 https://doi.org/10.1038/clpt.2010.238	journal	January 2011
A Comprehensive Hepatitis C Viral Kinetic Model Explaining Cure Snoeck, E.; Chanu, P.; Lavielle, M. Clinical Pharmacology & Therapeutics, Vol. 87, Issue 6 https://doi.org/10.1038/clpt.2010.35	journal	May 2010
A Pharmacokinetic–Viral Kinetic Model Describes the Effect of Alisporivir as Monotherapy or in Combination With Peg-IFN on Hepatitis C Virologic Response Nguyen, T. H. T.; Mentré, F.; Levi, M. Clinical Pharmacology & Therapeutics, Vol. 96, Issue 5 https://doi.org/10.1038/clpt.2014.173	journal	August 2014
Modelling how ribavirin improves interferon response rates in hepatitis C virus infection Dixit, Narendra M.; Layden-Almer, Jennifer E.; Layden, Thomas J. Nature, Vol. 432, Issue 7019 https://doi.org/10.1038/nature03153	journal	December 2004
Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect Gao, Min; Nettles, Richard E.; Belema, Makonen Nature, Vol. 465, Issue 7294 https://doi.org/10.1038/nature08960	journal	April 2010
A double whammy for hep C Farley, Suzanne Nature Reviews Drug Discovery, Vol. 2, Issue 6 https://doi.org/10.1038/nrd1116	journal	June 2003
Antiviral action of ribavirin in chronic hepatitis C Pawlotsky, Jean-Michel; Dahari, Harel; Neumann, Avidan U. Gastroenterology, Vol. 126, Issue 3 https://doi.org/10.1053/j.gastro.2003.12.002	journal	March 2004
Antiviral Suppression vs Restoration of RIG-I Signaling by Hepatitis C Protease and Polymerase Inhibitors Liang, Yuqiong; Ishida, Hisashi; Lenz, Oliver Gastroenterology, Vol. 135, Issue 5 https://doi.org/10.1053/j.gastro.2008.07.023	journal	November 2008
Rapid HCV-RNA Decline With Once Daily TMC435: A Phase I Study in Healthy Volunteers and Hepatitis C Patients Reesink, Henk W.; Fanning, Gregory C.; Farha, Khalid Abou Gastroenterology, Vol. 138, Issue 3 https://doi.org/10.1053/j.gastro.2009.10.033	journal	March 2010
Ribavirin Improves Early Responses to Peginterferon Through Improved Interferon Signaling Feld, Jordan J.; Lutchman, Glen A.; Heller, Theo Gastroenterology, Vol. 139, Issue 1 https://doi.org/10.1053/j.gastro.2010.03.037	journal	July 2010
Sporadic Reappearance of Minute Amounts of Hepatitis C Virus RNA After Successful Therapy Stimulates Cellular Immune Responses Veerapu, Naga Suresh; Raghuraman, Sukanya; Liang, T. Jake Gastroenterology, Vol. 140, Issue 2 https://doi.org/10.1053/j.gastro.2010.10.048	journal	February 2011
Is There a Role for Ribavirin in the Era of Hepatitis C Virus Direct-Acting Antivirals? Feld, Jordan J. Gastroenterology, Vol. 142, Issue 6 https://doi.org/10.1053/j.gastro.2011.12.064	journal	May 2012
Efficacy of Nucleotide Polymerase Inhibitor Sofosbuvir Plus the NS5A Inhibitor Ledipasvir or the NS5B Non-Nucleoside Inhibitor GS-9669 Against HCV Genotype 1 Infection Gane, Edward J.; Stedman, Catherine A.; Hyland, Robert H. Gastroenterology, Vol. 146, Issue 3 https://doi.org/10.1053/j.gastro.2013.11.007	journal	March 2014
Kinetic Analyses Reveal Potent and Early Blockade of Hepatitis C Virus Assembly by NS5A Inhibitors McGivern, David R.; Masaki, Takahiro; Williford, Sara Gastroenterology, Vol. 147, Issue 2 https://doi.org/10.1053/j.gastro.2014.04.021	journal	August 2014
Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon Herrmann, E. Hepatology, Vol. 37, Issue 6 https://doi.org/10.1053/jhep.2003.50218	journal	June 2003
Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis Kowdley, Kris V.; Gordon, Stuart C.; Reddy, K. Rajender New England Journal of Medicine, Vol. 370, Issue 20 https://doi.org/10.1056/NEJMoa1402355	journal	May 2014
Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life Guedj, J.; Dahari, H.; Rong, L. Proceedings of the National Academy of Sciences, Vol. 110, Issue 10 https://doi.org/10.1073/pnas.1203110110	journal	February 2013
Post-treatment control of HIV infection Conway, Jessica M.; Perelson, Alan S. Proceedings of the National Academy of Sciences, Vol. 112, Issue 17 https://doi.org/10.1073/pnas.1419162112	journal	April 2015
Correlation between the infectivity of hepatitis C virus in vivo and its infectivity in vitro. Shimizu, Y. K.; Purcell, R. H.; Yoshikura, H. Proceedings of the National Academy of Sciences, Vol. 90, Issue 13 https://doi.org/10.1073/pnas.90.13.6037	journal	July 1993
Interaction Index and Different Methods for Determining Drug Interaction in Combination Therapy Lee, J. J.; Kong, M.; Ayers, G. D. Journal of Biopharmaceutical Statistics, Vol. 17, Issue 3 https://doi.org/10.1080/10543400701199593	journal	May 2007
Differences in Viral Dynamics between Genotypes 1 and 2 of Hepatitis C Virus Neumann, Avidan U.; Lam, Nancy P.; Dahari, Harel The Journal of Infectious Diseases, Vol. 182, Issue 1 https://doi.org/10.1086/315661	journal	July 2000
Utility of Hepatitis C Viral Load Monitoring on Direct-Acting Antiviral Therapy Sidharthan, Sreetha; Kohli, Anita; Sims, Zayani Clinical Infectious Diseases, Vol. 60, Issue 12 https://doi.org/10.1093/cid/civ170	journal	March 2015
Interferon γ–Induced Protein10 Kinetics in Treatment-Naive Versus Treatment-Experienced Patients Receiving Interferon-Free Therapy for Hepatitis C Virus Infection: Implications for the Innate Immune Response Lin, Jennifer C.; Habersetzer, François; Rodriguez-Torres, Maribel The Journal of Infectious Diseases, Vol. 210, Issue 12 https://doi.org/10.1093/infdis/jiu325	journal	June 2014
Review article: predicting response in hepatitis C virus therapy Mihm, U.; Herrmann, E.; Sarrazin, C. Alimentary Pharmacology and Therapeutics, Vol. 23, Issue 8 https://doi.org/10.1111/j.1365-2036.2006.02863.x	journal	April 2006
Mericitabine and ritonavir-boosted danoprevir with or without ribavirin in treatment-naive HCV genotype 1 patients: INFORM-SVR study Gane, Edward J.; Pockros, Paul J.; Zeuzem, Stefan Liver International, Vol. 35, Issue 1 https://doi.org/10.1111/liv.12588	journal	June 2014
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time Perelson, A. S.; Neumann, A. U.; Markowitz, M. Science, Vol. 271, Issue 5255 https://doi.org/10.1126/science.271.5255.1582	journal	March 1996
Hepatitis C Viral Dynamics in Vivo and the Antiviral Efficacy of Interferon- Therapy Neumann, A. U. Science, Vol. 282, Issue 5386 https://doi.org/10.1126/science.282.5386.103	journal	October 1998
Rapid Emergence of Protease Inhibitor Resistance in Hepatitis C Virus Rong, L.; Dahari, H.; Ribeiro, R. M. Science Translational Medicine, Vol. 2, Issue 30 https://doi.org/10.1126/scitranslmed.3000544	journal	May 2010
Novel Hepatitis C Virus Reporter Replicon Cell Lines Enable Efficient Antiviral Screening against Genotype 1a Robinson, M.; Yang, H.; Sun, S. -C. Antimicrobial Agents and Chemotherapy, Vol. 54, Issue 8 https://doi.org/10.1128/AAC.00289-10	journal	June 2010
Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients Laouénan, Cédric; Marcellin, Patrick; Lapalus, Martine Antimicrobial Agents and Chemotherapy, Vol. 58, Issue 9 https://doi.org/10.1128/AAC.02611-14	journal	June 2014
Pharmacokinetic/Pharmacodynamic Predictors of Clinical Potency for Hepatitis C Virus Nonnucleoside Polymerase and Protease Inhibitors Reddy, Micaela B.; Morcos, Peter N.; Le Pogam, Sophie Antimicrobial Agents and Chemotherapy, Vol. 56, Issue 6 https://doi.org/10.1128/AAC.06283-11	journal	April 2012
Effect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo Cuevas, J. M.; Gonzalez-Candelas, F.; Moya, A. Journal of Virology, Vol. 83, Issue 11 https://doi.org/10.1128/JVI.00201-09	journal	March 2009
Mathematical Modeling of Subgenomic Hepatitis C Virus Replication in Huh-7 Cells Dahari, H.; Ribeiro, R. M.; Rice, C. M. Journal of Virology, Vol. 81, Issue 2 https://doi.org/10.1128/JVI.01304-06	journal	October 2006
Superinfection Exclusion in Cells Infected with Hepatitis C Virus Tscherne, D. M.; Evans, M. J.; von Hahn, T. Journal of Virology, Vol. 81, Issue 8 https://doi.org/10.1128/JVI.01748-06	journal	February 2007
Analysis of Hepatitis C Virus Superinfection Exclusion by Using Novel Fluorochrome Gene-Tagged Viral Genomes Schaller, T.; Appel, N.; Koutsoudakis, G. Journal of Virology, Vol. 81, Issue 9 https://doi.org/10.1128/JVI.02144-06	journal	February 2007
Evasion of Superinfection Exclusion and Elimination of Primary Viral RNA by an Adapted Strain of Hepatitis C Virus Webster, B.; Ott, M.; Greene, W. C. Journal of Virology, Vol. 87, Issue 24 https://doi.org/10.1128/JVI.02465-13	journal	October 2013
Modeling Subgenomic Hepatitis C Virus RNA Kinetics during Treatment with Alpha Interferon Dahari, H.; Sainz, B.; Perelson, A. S. Journal of Virology, Vol. 83, Issue 13 https://doi.org/10.1128/JVI.02612-08	journal	April 2009
Protease Inhibitors Block Multiple Functions of the NS3/4A Protease-Helicase during the Hepatitis C Virus Life Cycle McGivern, David R.; Masaki, Takahiro; Lovell, William Journal of Virology, Vol. 89, Issue 10 https://doi.org/10.1128/JVI.03188-14	journal	March 2015
Highly Permissive Cell Lines for Subgenomic and Genomic Hepatitis C Virus RNA Replication Blight, K. J.; McKeating, J. A.; Rice, C. M. Journal of Virology, Vol. 76, Issue 24 https://doi.org/10.1128/JVI.76.24.13001-13014.2002	journal	December 2002
Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C Rotman, Yaron; Noureddin, Mazen; Feld, Jordan J. Gut, Vol. 63, Issue 1 https://doi.org/10.1136/gutjnl-2012-303852	journal	February 2013
Analysis of Hepatitis C Virus Infection Models with Hepatocyte Homeostasis Reluga, Timothy C.; Dahari, Harel; Perelson, Alan S. SIAM Journal on Applied Mathematics, Vol. 69, Issue 4 https://doi.org/10.1137/080714579	journal	January 2009
Applying Regular Perturbation Analysis to HCV Viral Load Equations Saltzman, Jeffrey; Nachbar, Robert; Panorchan, Paul Proceedings of the 2009 SIAM Conference on “Mathematics for Industry” https://doi.org/10.1137/1.9781611973303.9	book	April 2010
Viral Kinetics in Patients with Chronic Hepatitis C Treated with the Serine Protease Inhibitor Biln 2061 Herrmann, Eva; Zeuzem, Stefan; Sarrazin, Christoph Antiviral Therapy, Vol. 11, Issue 3 https://doi.org/10.1177/135965350601100303	journal	April 2005
A Hepatitis C Viral Kinetic Model that Allows for Time-Varying Drug Effectiveness Shudo, Emi; Ribeiro, Ruy M.; Talal, Andrew H. Antiviral Therapy, Vol. 13, Issue 7 https://doi.org/10.1177/135965350801300711	journal	October 2008
Modelling Hepatitis C virus Kinetics: The Relationship between the Infected Cell Loss rate and the Final Slope of Viral Decay Dahari, Harel; Shudo, Emi; Cotler, Scott J. Antiviral Therapy, Vol. 14, Issue 3 https://doi.org/10.1177/135965350901400306	journal	April 2008
Rapid decrease of wild-type hepatitis C virus on telaprevir treatment Adiwijaya, Bambang S.; Hare, Brian; Caron, Paul R. Antiviral Therapy, Vol. 14, Issue 4 https://doi.org/10.1177/135965350901400402	journal	May 2008
A Multi-Variant, Viral Dynamic Model of Genotype 1 HCV to Assess the in vivo Evolution of Protease-Inhibitor Resistant Variants Adiwijaya, Bambang S.; Herrmann, Eva; Hare, Brian PLoS Computational Biology, Vol. 6, Issue 4 https://doi.org/10.1371/journal.pcbi.1000745	journal	April 2010
A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection Adiwijaya, Bambang S.; Kieffer, Tara L.; Henshaw, Joshua PLoS Computational Biology, Vol. 8, Issue 1 https://doi.org/10.1371/journal.pcbi.1002339	journal	January 2012
Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses Pawelek, Kasia A.; Huynh, Giao T.; Quinlivan, Michelle PLoS Computational Biology, Vol. 8, Issue 6 https://doi.org/10.1371/journal.pcbi.1002588	journal	June 2012
Analysis of Hepatitis C Virus Decline during Treatment with the Protease Inhibitor Danoprevir Using a Multiscale Model Rong, Libin; Guedj, Jeremie; Dahari, Harel PLoS Computational Biology, Vol. 9, Issue 3 https://doi.org/10.1371/journal.pcbi.1002959	journal	March 2013
A Hepatitis C Virus Infection Model with Time-Varying Drug Effectiveness: Solution and Analysis Conway, Jessica M.; Perelson, Alan S. PLoS Computational Biology, Vol. 10, Issue 8 https://doi.org/10.1371/journal.pcbi.1003769	journal	August 2014
Modeling Viral Evolutionary Dynamics after Telaprevir-Based Treatment Haseltine, Eric L.; De Meyer, Sandra; Dierynck, Inge PLoS Computational Biology, Vol. 10, Issue 8 https://doi.org/10.1371/journal.pcbi.1003772	journal	August 2014
Quantifying the Diversification of Hepatitis C Virus (HCV) during Primary Infection: Estimates of the In Vivo Mutation Rate Ribeiro, Ruy M.; Li, Hui; Wang, Shuyi PLoS Pathogens, Vol. 8, Issue 8 https://doi.org/10.1371/journal.ppat.1002881	journal	August 2012
Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study Sáez-Cirión, Asier; Bacchus, Charline; Hocqueloux, Laurent PLoS Pathogens, Vol. 9, Issue 3 https://doi.org/10.1371/journal.ppat.1003211	journal	March 2013
Replication Vesicles are Load- and Choke-Points in the Hepatitis C Virus Lifecycle Binder, Marco; Sulaimanov, Nurgazy; Clausznitzer, Diana PLoS Pathogens, Vol. 9, Issue 8 https://doi.org/10.1371/journal.ppat.1003561	journal	August 2013
Modeling HCV kinetics under therapy using PK and PD information Shudo, Emi; Ribeiro, Ruy M.; Perelson, Alan S. Expert Opinion on Drug Metabolism & Toxicology, Vol. 5, Issue 3 https://doi.org/10.1517/17425250902787616	journal	March 2009
Very late relapse after discontinuation of antiviral therapy for chronic hepatitis C Soriano, Vincent; Vispo, Eugenia; de Mendoza, Carmen Antiviral Therapy, Vol. 18, Issue 8 https://doi.org/10.3851/IMP2659	journal	January 2013
Analysis of the hepatitis C viral kinetics during administration of two nucleotide analogues: sofosbuvir (GS-7977) and GS-0938 Guedj, Jeremie; Pang, Phillip S.; Denning, Jill Antiviral Therapy, Vol. 19, Issue 2 https://doi.org/10.3851/IMP2733	journal	January 2014
Very late HCV relapse following triple therapy for hepatitis C Barreiro, Pablo; Vispo, Eugenia; Maida, Ivana Antiviral Therapy, Vol. 19, Issue 7 https://doi.org/10.3851/IMP2753	journal	January 2014
Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy Canini, Laetitia; DebRoy, Swati; Mariño, Zoe Antiviral Therapy, Vol. 20, Issue 2 https://doi.org/10.3851/IMP2806	journal	January 2014
A pharmacokinetic/viral kinetic model to evaluate the treatment effectiveness of danoprevir against chronic HCV Canini, Laetitia; Chatterjee, Anushree; Guedj, Jeremie Antiviral Therapy, Vol. 20, Issue 5 https://doi.org/10.3851/IMP2879	journal	January 2014

Cited By (22)

Mathematical Models for Immunology: Current State of the Art and Future Research Directions Eftimie, Raluca; Gillard, Joseph J.; Cantrell, Doreen A. Bulletin of Mathematical Biology, Vol. 78, Issue 10 https://doi.org/10.1007/s11538-016-0214-9	journal	October 2016
Ebola virus dynamics in mice treated with favipiravir Madelain, Vincent; Oestereich, Lisa; Graw, Frederik Antiviral Research, Vol. 123 https://doi.org/10.1016/j.antiviral.2015.08.015	journal	November 2015
The paradox of highly effective sofosbuvir-based combination therapy despite slow viral decline: can we still rely on viral kinetics? Nguyen, Thi Huyen Tram; Guedj, Jérémie; Uprichard, Susan L. Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-09776-z	journal	August 2017
Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges Baumert, Thomas F.; Berg, Thomas; Lim, Joseph K. Gastroenterology, Vol. 156, Issue 2 https://doi.org/10.1053/j.gastro.2018.10.024	journal	January 2019
Analysis of Practical Identifiability of a Viral Infection Model Nguyen, Van Kinh; Klawonn, Frank; Mikolajczyk, Rafael PLOS ONE, Vol. 11, Issue 12 https://doi.org/10.1371/journal.pone.0167568	journal	December 2016
Mathematical Analysis of Viral Replication Dynamics and Antiviral Treatment Strategies: From Basic Models to Age-Based Multi-Scale Modeling Zitzmann, Carolin; Kaderali, Lars Frontiers in Microbiology, Vol. 9 https://doi.org/10.3389/fmicb.2018.01546	journal	July 2018
Special Issue “Mathematical Modeling of Viral Infections” Murray, John; Ribeiro, Ruy Viruses, Vol. 10, Issue 6 https://doi.org/10.3390/v10060303	journal	June 2018
The design and statistical aspects of VIETNARMS: a strategic post-licensing trial of multiple oral direct acting antiviral Hepatitis C treatment strategies in Vietnam McCabe, L.; White, I. R.; Chau, N. V. Vinh arXiv https://doi.org/10.48550/arxiv.1911.02272	preprint	January 2019
Mathematical Models for Immunology: Current State of the Art and Future Research Directions Eftimie, Raluca; Gillard, Joseph J.; Cantrell, Doreen A. Bulletin of Mathematical Biology, Vol. 78, Issue 10 https://doi.org/10.1007/s11538-016-0214-9	journal	October 2016
Development of a Comprehensive Dataset of Hepatitis C Patients and Examination of Disease Epidemiology in the United States, 2013–2016 Chirikov, Viktor V.; Marx, Steven E.; Manthena, Shivaji R. Advances in Therapy, Vol. 35, Issue 7 https://doi.org/10.1007/s12325-018-0721-1	journal	June 2018
Management of acute HCV infection in the era of direct-acting antiviral therapy Martinello, Marianne; Hajarizadeh, Behzad; Grebely, Jason Nature Reviews Gastroenterology & Hepatology, Vol. 15, Issue 7 https://doi.org/10.1038/s41575-018-0026-5	journal	May 2018
Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies Best, Katharine; Guedj, Jeremie; Madelain, Vincent Proceedings of the National Academy of Sciences, Vol. 114, Issue 33 https://doi.org/10.1073/pnas.1704011114	journal	August 2017
Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus‐1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub‐study A5334s Venuto, Charles S.; Cramer, Yoninah S.; Rosenkranz, Susan L. British Journal of Clinical Pharmacology, Vol. 86, Issue 1 https://doi.org/10.1111/bcp.14148	journal	December 2019
Mathematical modeling of within-host Zika virus dynamics Best, Katharine; Perelson, Alan S. Immunological Reviews, Vol. 285, Issue 1 https://doi.org/10.1111/imr.12687	journal	August 2018
Interferon at the cellular, individual, and population level in hepatitis C virus infection: Its role in the interferon-free treatment era Raja, Rubesh; Baral, Subhasish; Dixit, Narendra M. Immunological Reviews, Vol. 285, Issue 1 https://doi.org/10.1111/imr.12689	journal	August 2018
Introduction to modeling viral infections and immunity Perelson, Alan S.; Ribeiro, Ruy M. Immunological Reviews, Vol. 285, Issue 1 https://doi.org/10.1111/imr.12700	journal	August 2018
Shortened therapy of eight weeks with paritaprevir/ritonavir/ombitasvir and dasabuvir is highly effective in people with recent HCV genotype 1 infection Martinello, M.; Bhagani, S.; Gane, E. Journal of Viral Hepatitis, Vol. 25, Issue 10 https://doi.org/10.1111/jvh.12917	journal	May 2018
Incidence and predictors of direct-acting antiviral treatment failure in Turkish patients with chronic hepatitis C genotype 1b infection Cabalak, Mehmet; Bal, Tayibe; Onlen, Yusuf Tropical Doctor, Vol. 50, Issue 2 https://doi.org/10.1177/0049475519892082	journal	December 2019
The design and statistical aspects of VIETNARMS: a strategic post-licensing trial of multiple oral direct-acting antiviral hepatitis C treatment strategies in Vietnam McCabe, Leanne; White, Ian R.; Chau, Nguyen Van Vinh Trials, Vol. 21, Issue 1 https://doi.org/10.1186/s13063-020-04350-x	journal	May 2020
Modelling how responsiveness to interferon improves interferon-free treatment of hepatitis C virus infection Venugopal, Vishnu; Padmanabhan, Pranesh; Raja, Rubesh PLOS Computational Biology, Vol. 14, Issue 7 https://doi.org/10.1371/journal.pcbi.1006335	journal	July 2018
Mutational pathway maps and founder effects define the within-host spectrum of hepatitis C virus mutants resistant to drugs Raja, Rubesh; Pareek, Aditya; Newar, Kapil PLOS Pathogens, Vol. 15, Issue 4 https://doi.org/10.1371/journal.ppat.1007701	journal	April 2019
Special Issue “Mathematical Modeling of Viral Infections” Murray, John; Ribeiro, Ruy Viruses, Vol. 10, Issue 6 https://doi.org/10.3390/v10060303	journal	June 2018

Similar Records

Analysis of Hepatitis C Virus Decline during Treatment with the Protease Inhibitor Danoprevir Using a Multiscale Model

Journal Article · Thu Mar 14 04:00:00 UTC 2013 · PLoS Computational Biology (Online) · OSTI ID:1321717

Rong, Libin; Guedj, Jeremie; Dahari, Harel; +4 more

Second-Phase Hepatitis C Plasma Viral Kinetics Directly Reflects Reduced Intrahepatic Burden of Hepatitis C Virus

Journal Article · Wed Feb 01 04:00:00 UTC 2023 · Journal of Infectious Diseases · OSTI ID:2367479

Sachithanandham, Jaiprasath; Balagopal, Ashwin; Leep-Lazar, Julia; +5 more

Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice

Journal Article · Fri Jun 15 04:00:00 UTC 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23137119

Teraoka, Yuji; Uchida, Takuro; Imamura, Michio; +3 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biological Science

Title: Modelling hepatitis C therapy—predicting effects of treatment

Citation Formats

References (90)

Cited By (22)

Similar Records

Related Subjects