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

Abstract

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.

Authors:

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)

Publication Date:: 2015-06-30

Research Org.:: Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1236682

Report Number(s):: LA-UR-15-20073
Journal ID: ISSN 1759-5045

Grant/Contract Number:: AC52-06NA25396

Resource Type:: Journal Article: Accepted Manuscript

Journal Name:: Nature Reviews. Gastroenterology & Hepatology

Additional Journal Information:: Journal Volume: 12; Journal Issue: 8; Journal ID: ISSN 1759-5045

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Biological Science

Citation Formats


                    Perelson, Alan S., and Guedj, Jeremie. Modelling hepatitis C therapy—predicting effects of treatment.  United States: N. p., 2015. 
        Web.  doi:10.1038/nrgastro.2015.97.

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                    Perelson, Alan S., & Guedj, Jeremie. Modelling hepatitis C therapy—predicting effects of treatment.  United States.  https://doi.org/10.1038/nrgastro.2015.97

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                    Perelson, Alan S., and Guedj, Jeremie. 2015.  
        "Modelling hepatitis C therapy—predicting effects of treatment".  United States.  https://doi.org/10.1038/nrgastro.2015.97.  https://www.osti.gov/servlets/purl/1236682.

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@article{osti_1236682,

  title        = {Modelling hepatitis C therapy—predicting effects of treatment},

  author       = {Perelson, Alan S. and Guedj, Jeremie},

  abstractNote = {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.},

  doi          = {10.1038/nrgastro.2015.97},

  url          = {https://www.osti.gov/biblio/1236682},
  journal      = {Nature Reviews. Gastroenterology & Hepatology},

  issn         = {1759-5045},

  number       = 8,

  volume       = 12,

  place        = {United States},

  year         = {2015},

  month        = {6}

}

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Soriano, Vincent; Vispo, Eugenia; de Mendoza, Carmen
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Very late HCV relapse following triple therapy for hepatitis C
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Barreiro, Pablo; Vispo, Eugenia; Maida, Ivana
Antiviral Therapy, Vol. 19, Issue 7
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Sporadic Reappearance of Minute Amounts of Hepatitis C Virus RNA After Successful Therapy Stimulates Cellular Immune Responses
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Gastroenterology, Vol. 140, Issue 2
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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
journal, June 2014

Lin, Jennifer C.; Habersetzer, François; Rodriguez-Torres, Maribel
The Journal of Infectious Diseases, Vol. 210, Issue 12
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Mathematical Models for Immunology: Current State of the Art and Future Research Directions
journal, October 2016

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

Development of a Comprehensive Dataset of Hepatitis C Patients and Examination of Disease Epidemiology in the United States, 2013–2016
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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

Management of acute HCV infection in the era of direct-acting antiviral therapy
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Martinello, Marianne; Hajarizadeh, Behzad; Grebely, Jason
Nature Reviews Gastroenterology & Hepatology, Vol. 15, Issue 7
https://doi.org/10.1038/s41575-018-0026-5

Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies
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Best, Katharine; Guedj, Jeremie; Madelain, Vincent
Proceedings of the National Academy of Sciences, Vol. 114, Issue 33
https://doi.org/10.1073/pnas.1704011114

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
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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

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Best, Katharine; Perelson, Alan S.
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https://doi.org/10.1111/imr.12687

Interferon at the cellular, individual, and population level in hepatitis C virus infection: Its role in the interferon-free treatment era
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Raja, Rubesh; Baral, Subhasish; Dixit, Narendra M.
Immunological Reviews, Vol. 285, Issue 1
https://doi.org/10.1111/imr.12689

Introduction to modeling viral infections and immunity
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Perelson, Alan S.; Ribeiro, Ruy M.
Immunological Reviews, Vol. 285, Issue 1
https://doi.org/10.1111/imr.12700

Shortened therapy of eight weeks with paritaprevir/ritonavir/ombitasvir and dasabuvir is highly effective in people with recent HCV genotype 1 infection
journal, May 2018

Martinello, M.; Bhagani, S.; Gane, E.
Journal of Viral Hepatitis, Vol. 25, Issue 10
https://doi.org/10.1111/jvh.12917

Incidence and predictors of direct-acting antiviral treatment failure in Turkish patients with chronic hepatitis C genotype 1b infection
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Cabalak, Mehmet; Bal, Tayibe; Onlen, Yusuf
Tropical Doctor, Vol. 50, Issue 2
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The design and statistical aspects of VIETNARMS: a strategic post-licensing trial of multiple oral direct-acting antiviral hepatitis C treatment strategies in Vietnam
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McCabe, Leanne; White, Ian R.; Chau, Nguyen Van Vinh
Trials, Vol. 21, Issue 1
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PLOS Computational Biology, Vol. 14, Issue 7
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Mutational pathway maps and founder effects define the within-host spectrum of hepatitis C virus mutants resistant to drugs
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Viruses, Vol. 10, Issue 6
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Title: Modelling hepatitis C therapy—predicting effects of treatment

Abstract

Citation Formats

Efficacy of Nucleotide Polymerase Inhibitor Sofosbuvir Plus the NS5A Inhibitor Ledipasvir or the NS5B Non-Nucleoside Inhibitor GS-9669 Against HCV Genotype 1 Infection journal, March 2014

Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection journal, January 1995

Decay characteristics of HIV-1-infected compartments during combination therapy journal, May 1997

HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time journal, March 1996

Viral dynamics in human immunodeficiency virus type 1 infection journal, January 1995

Hepatitis C Viral Dynamics in Vivo and the Antiviral Efficacy of Interferon- Therapy journal, October 1998

Modeling Subgenomic Hepatitis C Virus RNA Kinetics during Treatment with Alpha Interferon journal, April 2009

Mathematical analysis of multiscale models for hepatitis C virus dynamics under therapy with direct-acting antiviral agents journal, September 2013

Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon journal, June 2003

Modelling how ribavirin improves interferon response rates in hepatitis C virus infection journal, December 2004

Antiviral action of ribavirin in chronic hepatitis C journal, March 2004

Pharmacodynamics of PEG-IFN α differentiate HIV/HCV coinfected sustained virological responders from nonresponders journal, May 2006

Triphasic decline of hepatitis C virus RNA during antiviral therapy journal, January 2007

Modeling hepatitis C virus dynamics: Liver regeneration and critical drug efficacy journal, July 2007

Analysis of Hepatitis C Virus Infection Models with Hepatocyte Homeostasis journal, January 2009

Pharmacodynamics of PEG-IFN-α-2a in HIV/HCV co-infected patients: Implications for treatment outcomes journal, September 2010

Hepatocyte Proliferation and Hepatitis C Virus Kinetics During Treatment journal, January 2011

Pharmacokinetic/Pharmacodynamic Predictors of Clinical Potency for Hepatitis C Virus Nonnucleoside Polymerase and Protease Inhibitors journal, April 2012

A Pharmacokinetic–Viral Kinetic Model Describes the Effect of Alisporivir as Monotherapy or in Combination With Peg-IFN on Hepatitis C Virologic Response journal, August 2014

HCV Kinetic Models and Their Implications in Drug Development: HCV Kinetic Models and Their Implications journal, April 2015

The metabolism, pharmacokinetics and mechanisms of antiviral activity of ribavirin against hepatitis C virus journal, February 2006

Is There a Role for Ribavirin in the Era of Hepatitis C Virus Direct-Acting Antivirals? journal, May 2012

Ribavirin Improves Early Responses to Peginterferon Through Improved Interferon Signaling journal, July 2010

Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C journal, February 2013

Ribavirin potentiates interferon action by augmenting interferon-stimulated gene induction in hepatitis C virus cell culture models journal, October 2010

Review article: predicting response in hepatitis C virus therapy journal, April 2006

A pharmacokinetic/viral kinetic model to evaluate the treatment effectiveness of danoprevir against chronic HCV journal, January 2014

A Hepatitis C Virus Infection Model with Time-Varying Drug Effectiveness: Solution and Analysis journal, August 2014

Modeling HCV kinetics under therapy using PK and PD information journal, March 2009

Second-phase hepatitis C virus RNA decline during telaprevir-based therapy increases with drug effectiveness: Implications for treatment duration journal, May 2011

Hepatitis C viral kinetics with the nucleoside polymerase inhibitor mericitabine (RG7128) journal, February 2012

Analysis of the hepatitis C viral kinetics during administration of two nucleotide analogues: sofosbuvir (GS-7977) and GS-0938 journal, January 2014

Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy journal, January 2014

Viral kinetic modeling: state of the art journal, June 2014

Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect journal, April 2010

Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life journal, February 2013

Differences in Viral Dynamics between Genotypes 1 and 2 of Hepatitis C Virus journal, July 2000

Analysis of Hepatitis C Virus Decline during Treatment with the Protease Inhibitor Danoprevir Using a Multiscale Model journal, March 2013

Kinetic Analyses Reveal Potent and Early Blockade of Hepatitis C Virus Assembly by NS5A Inhibitors journal, August 2014

Protease Inhibitors Block Multiple Functions of the NS3/4A Protease-Helicase during the Hepatitis C Virus Life Cycle journal, March 2015

Type I interferon rapidly restricts infectious hepatitis C virus particle genesis journal, September 2014

Mathematical Modeling of Subgenomic Hepatitis C Virus Replication in Huh-7 Cells journal, October 2006

Replication Vesicles are Load- and Choke-Points in the Hepatitis C Virus Lifecycle journal, August 2013

A Comprehensive Hepatitis C Viral Kinetic Model Explaining Cure journal, May 2010

Rapid HCV-RNA Decline With Once Daily TMC435: A Phase I Study in Healthy Volunteers and Hepatitis C Patients journal, March 2010

Highly Permissive Cell Lines for Subgenomic and Genomic Hepatitis C Virus RNA Replication journal, December 2002

Novel Hepatitis C Virus Reporter Replicon Cell Lines Enable Efficient Antiviral Screening against Genotype 1a journal, June 2010

A double whammy for hep C journal, June 2003

Antiviral Suppression vs Restoration of RIG-I Signaling by Hepatitis C Protease and Polymerase Inhibitors journal, November 2008

Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics: A Randomized Clinical Trial journal, August 2013

Understanding hepatitis C viral dynamics with direct-acting antiviral agents due to the interplay between intracellular replication and cellular infection dynamics journal, December 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 journal, June 2014

Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice journal, March 2015

Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study journal, March 2015

Importance of very early HCV RNA kinetics for prediction of treatment outcome of highly effective all oral direct acting antiviral combination therapy journal, March 2015

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 journal, October 2010

Mericitabine and ritonavir-boosted danoprevir with or without ribavirin in treatment-naive HCV genotype 1 patients: INFORM-SVR study journal, June 2014

Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis journal, May 2014

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 journal, March 2008

A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection journal, January 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. journal, April 2014

Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients journal, September 2007

A Multi-Variant, Viral Dynamic Model of Genotype 1 HCV to Assess the in vivo Evolution of Protease-Inhibitor Resistant Variants journal, April 2010

Quantifying the Diversification of Hepatitis C Virus (HCV) during Primary Infection: Estimates of the In Vivo Mutation Rate journal, August 2012

Effect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo journal, March 2009

Rapid Emergence of Protease Inhibitor Resistance in Hepatitis C Virus journal, May 2010

Modeling Viral Evolutionary Dynamics after Telaprevir-Based Treatment journal, August 2014

Modeling Quasispecies and Drug Resistance in Hepatitis C Patients Treated with a Protease Inhibitor journal, May 2012

Analysis of Hepatitis C Virus Superinfection Exclusion by Using Novel Fluorochrome Gene-Tagged Viral Genomes journal, February 2007

Superinfection Exclusion in Cells Infected with Hepatitis C Virus journal, February 2007

Evasion of Superinfection Exclusion and Elimination of Primary Viral RNA by an Adapted Strain of Hepatitis C Virus journal, October 2013

Characterization of hepatitis C virus intergenotypic recombinant strains and associated virological response to sofosbuvir/ribavirin journal, December 2014

Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses journal, June 2012

Interaction Index and Different Methods for Determining Drug Interaction in Combination Therapy journal, May 2007

1172 Antiviral Activity and Resistance Profile of the Novel hcv ns5a Inhibitor Gs-5885 journal, April 2012

Utility of Hepatitis C Viral Load Monitoring on Direct-Acting Antiviral Therapy journal, March 2015

Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study journal, March 2013

Efficacy of Nucleotide Polymerase Inhibitor Sofosbuvir Plus the NS5A Inhibitor Ledipasvir or the NS5B Non-Nucleoside Inhibitor GS-9669 Against HCV Genotype 1 Infection
journal, March 2014

Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection
journal, January 1995

Decay characteristics of HIV-1-infected compartments during combination therapy
journal, May 1997

HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time
journal, March 1996

Viral dynamics in human immunodeficiency virus type 1 infection
journal, January 1995

Hepatitis C Viral Dynamics in Vivo and the Antiviral Efficacy of Interferon- Therapy
journal, October 1998

Modeling Subgenomic Hepatitis C Virus RNA Kinetics during Treatment with Alpha Interferon
journal, April 2009

Mathematical analysis of multiscale models for hepatitis C virus dynamics under therapy with direct-acting antiviral agents
journal, September 2013

Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon
journal, June 2003

Modelling how ribavirin improves interferon response rates in hepatitis C virus infection
journal, December 2004

Antiviral action of ribavirin in chronic hepatitis C
journal, March 2004

Pharmacodynamics of PEG-IFN α differentiate HIV/HCV coinfected sustained virological responders from nonresponders
journal, May 2006

Triphasic decline of hepatitis C virus RNA during antiviral therapy
journal, January 2007

Modeling hepatitis C virus dynamics: Liver regeneration and critical drug efficacy
journal, July 2007

Analysis of Hepatitis C Virus Infection Models with Hepatocyte Homeostasis
journal, January 2009

Pharmacodynamics of PEG-IFN-α-2a in HIV/HCV co-infected patients: Implications for treatment outcomes
journal, September 2010

Hepatocyte Proliferation and Hepatitis C Virus Kinetics During Treatment
journal, January 2011

Pharmacokinetic/Pharmacodynamic Predictors of Clinical Potency for Hepatitis C Virus Nonnucleoside Polymerase and Protease Inhibitors
journal, April 2012

A Pharmacokinetic–Viral Kinetic Model Describes the Effect of Alisporivir as Monotherapy or in Combination With Peg-IFN on Hepatitis C Virologic Response
journal, August 2014

HCV Kinetic Models and Their Implications in Drug Development: HCV Kinetic Models and Their Implications
journal, April 2015

The metabolism, pharmacokinetics and mechanisms of antiviral activity of ribavirin against hepatitis C virus
journal, February 2006

Is There a Role for Ribavirin in the Era of Hepatitis C Virus Direct-Acting Antivirals?
journal, May 2012

Ribavirin Improves Early Responses to Peginterferon Through Improved Interferon Signaling
journal, July 2010

Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C
journal, February 2013

Ribavirin potentiates interferon action by augmenting interferon-stimulated gene induction in hepatitis C virus cell culture models
journal, October 2010

Review article: predicting response in hepatitis C virus therapy
journal, April 2006

A pharmacokinetic/viral kinetic model to evaluate the treatment effectiveness of danoprevir against chronic HCV
journal, January 2014

A Hepatitis C Virus Infection Model with Time-Varying Drug Effectiveness: Solution and Analysis
journal, August 2014

Modeling HCV kinetics under therapy using PK and PD information
journal, March 2009

Second-phase hepatitis C virus RNA decline during telaprevir-based therapy increases with drug effectiveness: Implications for treatment duration
journal, May 2011

Hepatitis C viral kinetics with the nucleoside polymerase inhibitor mericitabine (RG7128)
journal, February 2012

Analysis of the hepatitis C viral kinetics during administration of two nucleotide analogues: sofosbuvir (GS-7977) and GS-0938
journal, January 2014

Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy
journal, January 2014

Viral kinetic modeling: state of the art
journal, June 2014

Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect
journal, April 2010

Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life
journal, February 2013

Differences in Viral Dynamics between Genotypes 1 and 2 of Hepatitis C Virus
journal, July 2000

Analysis of Hepatitis C Virus Decline during Treatment with the Protease Inhibitor Danoprevir Using a Multiscale Model
journal, March 2013

Kinetic Analyses Reveal Potent and Early Blockade of Hepatitis C Virus Assembly by NS5A Inhibitors
journal, August 2014

Protease Inhibitors Block Multiple Functions of the NS3/4A Protease-Helicase during the Hepatitis C Virus Life Cycle
journal, March 2015

Type I interferon rapidly restricts infectious hepatitis C virus particle genesis
journal, September 2014

Mathematical Modeling of Subgenomic Hepatitis C Virus Replication in Huh-7 Cells
journal, October 2006

Replication Vesicles are Load- and Choke-Points in the Hepatitis C Virus Lifecycle
journal, August 2013

A Comprehensive Hepatitis C Viral Kinetic Model Explaining Cure
journal, May 2010

Rapid HCV-RNA Decline With Once Daily TMC435: A Phase I Study in Healthy Volunteers and Hepatitis C Patients
journal, March 2010

Highly Permissive Cell Lines for Subgenomic and Genomic Hepatitis C Virus RNA Replication
journal, December 2002

Novel Hepatitis C Virus Reporter Replicon Cell Lines Enable Efficient Antiviral Screening against Genotype 1a
journal, June 2010

A double whammy for hep C
journal, June 2003

Antiviral Suppression vs Restoration of RIG-I Signaling by Hepatitis C Protease and Polymerase Inhibitors
journal, November 2008

Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics: A Randomized Clinical Trial
journal, August 2013

Understanding hepatitis C viral dynamics with direct-acting antiviral agents due to the interplay between intracellular replication and cellular infection dynamics
journal, December 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
journal, June 2014

Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice
journal, March 2015

Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study
journal, March 2015

Importance of very early HCV RNA kinetics for prediction of treatment outcome of highly effective all oral direct acting antiviral combination therapy
journal, March 2015

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
journal, October 2010

Mericitabine and ritonavir-boosted danoprevir with or without ribavirin in treatment-naive HCV genotype 1 patients: INFORM-SVR study
journal, June 2014

Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis
journal, May 2014

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
journal, March 2008

A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection
journal, January 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.
journal, April 2014

Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients
journal, September 2007

A Multi-Variant, Viral Dynamic Model of Genotype 1 HCV to Assess the in vivo Evolution of Protease-Inhibitor Resistant Variants
journal, April 2010

Quantifying the Diversification of Hepatitis C Virus (HCV) during Primary Infection: Estimates of the In Vivo Mutation Rate
journal, August 2012

Effect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo
journal, March 2009

Rapid Emergence of Protease Inhibitor Resistance in Hepatitis C Virus
journal, May 2010

Modeling Viral Evolutionary Dynamics after Telaprevir-Based Treatment
journal, August 2014

Modeling Quasispecies and Drug Resistance in Hepatitis C Patients Treated with a Protease Inhibitor
journal, May 2012

Analysis of Hepatitis C Virus Superinfection Exclusion by Using Novel Fluorochrome Gene-Tagged Viral Genomes
journal, February 2007

Superinfection Exclusion in Cells Infected with Hepatitis C Virus
journal, February 2007

Evasion of Superinfection Exclusion and Elimination of Primary Viral RNA by an Adapted Strain of Hepatitis C Virus
journal, October 2013

Characterization of hepatitis C virus intergenotypic recombinant strains and associated virological response to sofosbuvir/ribavirin
journal, December 2014

Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses
journal, June 2012

Interaction Index and Different Methods for Determining Drug Interaction in Combination Therapy
journal, May 2007

1172 Antiviral Activity and Resistance Profile of the Novel hcv ns5a Inhibitor Gs-5885
journal, April 2012

Utility of Hepatitis C Viral Load Monitoring on Direct-Acting Antiviral Therapy
journal, March 2015

Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study
journal, March 2013

Post-treatment control of HIV infection
journal, April 2015

Correlation between the infectivity of hepatitis C virus in vivo and its infectivity in vitro.
journal, July 1993

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
journal, July 2013