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Title: Modelling hepatitis C therapy—predicting effects of treatment

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:
 [1] ;  [2]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. INSERM, IAME, UMR, Univ. Paris Diderot, Paris (France)
Publication Date:
OSTI Identifier:
1236682
Report Number(s):
LA-UR--15-20073
Journal ID: ISSN 1759-5045; nrgastro.2015.97
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Nature Reviews. Gastroenterology & Hepatology
Additional Journal Information:
Journal Volume: 12; Journal Issue: 8; Journal ID: ISSN 1759-5045
Publisher:
Nature Publishing Group
Research Org:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES biomarkers; drug therapy; Hepatitis C; infection