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Title: Modelling hepatitis C therapy—predicting effects of treatment

Journal Article · · Nature Reviews. Gastroenterology & Hepatology
 [1];  [2]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. 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.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1236682
Report Number(s):
LA-UR-15-20073
Journal Information:
Nature Reviews. Gastroenterology & Hepatology, Vol. 12, Issue 8; ISSN 1759-5045
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 61 works
Citation information provided by
Web of Science

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Cited By (20)

Modelling how responsiveness to interferon improves interferon-free treatment of hepatitis C virus infection journal July 2018
Mathematical Analysis of Viral Replication Dynamics and Antiviral Treatment Strategies: From Basic Models to Age-Based Multi-Scale Modeling journal July 2018
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
Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies 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 journal December 2019
Special Issue “Mathematical Modeling of Viral Infections” journal June 2018
Mathematical Models for Immunology: Current State of the Art and Future Research Directions journal October 2016
Incidence and predictors of direct-acting antiviral treatment failure in Turkish patients with chronic hepatitis C genotype 1b infection journal December 2019
Analysis of Practical Identifiability of a Viral Infection Model journal December 2016
The design and statistical aspects of VIETNARMS: a strategic post-licensing trial of multiple oral direct acting antiviral Hepatitis C treatment strategies in Vietnam preprint January 2019
Management of acute HCV infection in the era of direct-acting antiviral therapy journal May 2018
Introduction to modeling viral infections and immunity journal August 2018
Ebola virus dynamics in mice treated with favipiravir journal November 2015
The paradox of highly effective sofosbuvir-based combination therapy despite slow viral decline: can we still rely on viral kinetics? journal August 2017
Development of a Comprehensive Dataset of Hepatitis C Patients and Examination of Disease Epidemiology in the United States, 2013–2016 journal June 2018
Mutational pathway maps and founder effects define the within-host spectrum of hepatitis C virus mutants resistant to drugs journal April 2019
Interferon at the cellular, individual, and population level in hepatitis C virus infection: Its role in the interferon-free treatment era journal August 2018
Mathematical modeling of within-host Zika virus dynamics journal August 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 journal May 2020
Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges journal January 2019

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