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

PLoS Computational Biology

Volumn 9, Issue 3, 2013, Pages

  Rong, Libin ^a   Guedj, Jeremie ^b,c,d   Dahari, Harel ^b,e,f   Coffield, Daniel J ^g   Levi, Micha ^h,i   Smith, Patrick ^h   Perelson, Alan S ^b  

^a OAKLAND UNIVERSITY   (United States)

^b LOS ALAMOS NATIONAL LABORATORY   (United States)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d INSERM   (France)

^e UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^f LOYOLA UNIVERSITY CHICAGO   (United States)

^g UNIVERSITY OF MICHIGAN FLINT   (United States)

^h HOFFMANN LA ROCHE INC   (United States)

ⁱ NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRAL AGENTS; BODY FLUIDS; DRUG THERAPY; DYNAMICS; PATIENT MONITORING; PHYSIOLOGY; RNA;

'CURRENT; DYNAMICS MODELS; HEPATITIS C VIRUS; INFECTED CELLS; KEEP TRACK OF; MEANS EFFECTIVENESS; MULTISCALE MODELING; PROTEASE INHIBITOR; VIRAL RNA; VIRUS DYNAMICS;

VIRUSES;

DANOPREVIR; VIRUS RNA;

ANTIVIRAL ACTIVITY; ARTICLE; CALCULATION; CONTROLLED STUDY; DRUG MECHANISM; HEPATITIS C; HUMAN; IN VIVO STUDY; MATHEMATICAL COMPUTING; MATHEMATICAL MODEL; MULTISCALE MODEL; RNA DEGRADATION; RNA SYNTHESIS; TREATMENT DURATION; VIRAL CLEARANCE; VIRUS ASSEMBLY; VIRUS LOAD; VIRUS REPLICATION;

EID: 84876003551     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1002959     Document Type: Article

References (52)

1. World Health Organization. Hepatitis C. Fact sheet No. 164. Revised June 2011. http://www.who.int/mediacentre/factsheets/fs164/en/index.html.
2. Cardoso AC, Moucari R, Figueiredo-Mendes C, Ripault MP, Giuily N, et al. (2010) Impact of peginterferon and ribavirin therapy on hepatocellular carcinoma: incidence and survival in hepatitis C patients with advanced fibrosis. J Hepatol 52: 652-7.
3. Awad T, Thorlund K, Hauser G, Stimac D, Mabrouk M, et al. (2010) Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: systematic review of randomized trials. Hepatology 51: 1176-84.
4. Poordad F, McCone JJ, Bacon BR, Bruno S, Manns MP, et al. (2011) Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 364: 1195-206.
5. Hezode C, Forestier N, Dusheiko G, Ferenci P, Pol S, et al. (2009) Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 360: 1839-50.
6. McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, et al. (2009) Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 360: 1827-38.
7. Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, et al. (2011) Responseguided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med 365: 1014-24.
8. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, et al. (2011) Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 364: 1207-17.
9. Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, et al. (1998) Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 282: 103-7.
10. Dixit NM, Layden-Almer JE, Layden TJ, Perelson AS, (2004) Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature 432: 922-4.
11. Guedj J, Rong L, Dahari H, Perelson AS, (2010) A perspective on modelling hepatitis C virus infection. J Viral Hepat 17: 825-33.
12. Rong L, Perelson AS, (2010) Treatment of hepatitis C virus infection with interferon and small molecule direct antivirals: viral kinetics and modeling. Crit Rev Immunol 30: 131-48.
13. Guedj J, Neumann AU, (2010) Understanding hepatitis C viral dynamics with direct-acting antiviral agents due to the interplay between intracellular replication and cellular infection dynamics. J Theor Biol 267: 330-40.
14. Guedj J, Dahari H, Rong L, Sansone N, Nettles RE, et al. (2012) Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc Natl Acad Sci USA doi:10.1073/pnas.1203110110,.
15. Forestier N, Larrey D, Guyader D, Marcellin P, Rouzier R, et al. (2011) Treatment of chronic hepatitis C patients with the NS3/4A protease inhibitor danoprevir (ITMN-191/RG7227) leads to robust reductions in viral RNA: a phase 1b multiple ascending dose study. J Hepatol 54: 1130-6.
16. Neumann AU, Lam NP, Dahari H, Davidian M, Wiley TE, et al. (2000) Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus. J Infect Dis 182: 28-35.
17. Sherman KE, Shire NJ, Rouster SD, Peters MG, James Koziel M, et al. (2005) Viral kinetics in hepatitis C or hepatitis C/human immunodeficiency virus-infected patients. Gastroenterology 128: 313-27.
18. Adiwijaya BS, Hare B, Caron PR, Randle JC, Neumann AU, et al. (2009) Rapid decrease of wild-type hepatitis C virus on telaprevir treatment. Antivir Ther 14: 591-5.
19. Dahari H, Sainz JB, Perelson AS, Uprichard SL, (2009) Modeling subgenomic hepatitis C virus RNA kinetics during treatment with alpha interferon. J Virol 83: 6383-90.
20. Dahari H, Ribeiro RM, Rice CM, Perelson AS, (2007) Mathematical modeling of subgenomic hepatitis C virus replication in Huh-7 cells. J Virol 81: 750-60.
21. Marquardt DW, (1963) An algorithm for least-squares estimation of nonlinear parameters. J Soc Indust Appl Math 11: 431-41.
22. Lin K, Kwong AD, Lin C, (2004) Combination of a hepatitis C virus NS3-NS4A protease inhibitor and alpha interferon synergistically inhibits viral RNA replication and facilitates viral RNA clearance in replicon cells. Antimicrob Agents Chemother 48: 4784-92.
23. Blight KJ, McKeating JA, Rice CM, (2002) Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. J Virol 76: 13001-14.
24. Nelson PW, Gilchrist MA, Coombs D, Hyman JM, Perelson AS, (2004) An age-structured model of hiv infection that allows for variations in the production rate of viral particles and the death rate of productively infected cells. Math Biosci Eng 1: 267-88.
25. Rong L, Feng Z, Perelson AS, (2007) Mathematical analysis of age-structured HIV-1 dynamics with combination antiretroviral therapy. SIAM J Appl Math 67: 731-56.
26. Dahari H, Barretto N, Sainz BJ, Guedj J, Perelson AS, et al. (2011) Modeling interferonalpha mediated inhibition kinetics of intracellular and extracellular HCV RNA during HCV infection in vitro. J Hepatol 54: S312.
27. Shimakami T, Welsch C, Yamane D, McGivern DR, Yi M, et al. (2011) Protease inhibitorresistant hepatitis C virus mutants with reduced fitness from impaired production of infectious virus. Gastroenterology 140: 667-75.
28. Fusco DN, Chung RT, (2012) Novel therapies for hepatitis C: insights from the structure of the virus. Annu Rev Med 63: 373-87.
29. Hoofnagle JH, (2009) A step forward in therapy for hepatitis C. N Engl J Med 360: 1899-901.
30. Rong L, Dahari H, Ribeiro RM, Perelson AS, (2010) Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2: 30ra32.
31. Ciesek S, von Hahn T, Manns MP, (2011) Second-wave protease inhibitors: choosing an heir. Clin Liver Dis 15: 597-609.
32. Schaefer EA, Chung RT, (2012) Anti-hepatitis C virus drugs in development. Gastroenterology 142: 1340-1350 e1.
33. Gane EJ, Rouzier R, Stedman C, Wiercinska-Drapalo A, Horban A, et al. (2011) Antiviral activity, safety, and pharmacokinetics of danoprevir/ritonavir plus PEG-IFN alpha-2a/RBV in hepatitis C patients. J Hepatol 55: 972-9.
34. Forestier N, Larrey D, Marcellin P, Guyader D, Patat A, et al. (2011) Antiviral activity of danoprevir (ITMN-191/RG7227) in combination with pegylated interferon alpha-2a and ribavirin in patients with hepatitis C. J Infect Dis 204: 601-8.
35. Gane EJ, Roberts SK, Stedman CA, Angus PW, Ritchie B, et al. (2010) 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, doseescalation trial. Lancet 376: 1467-75.
36. Snoeck E, Chanu P, Lavielle M, Jacqmin P, Jonsson EN, et al. (2010) A comprehensive hepatitis C viral kinetic model explaining cure. Clin Pharmacol Ther 87: 706-13.
37. Powers KA, Ribeiro RM, Patel K, Pianko S, Nyberg L, et al. (2006) Kinetics of hepatitis C virus reinfection after liver transplantation. Liver Transpl 12: 207-16.
38. Dahari H, Feliu A, Garcia-Retortillo M, Forns X, Neumann AU, (2005) Second hepatitis C replication compartment indicated by viral dynamics during liver transplantation. J Hepatol 42: 491-8.
39. Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, et al. (2010) Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 465: 96-100.
40. Dustin LB, Rice CM, (2007) Flying under the radar: the immunobiology of hepatitis C. Annu Rev Immunol 25: 71-99.
41. Akira S, Uematsu S, Takeuchi O, (2006) Pathogen recognition and innate immunity. Cell 124: 783-801.
42. Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC, et al. (2005) Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci USA 102: 2992-7.
43. Foy E, Li K, Wang C, Sumpter J R, Ikeda M, et al. (2003) Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 300: 1145-8.
44. Taylor DR, Puig M, Darnell ME, Mihalik K, Feinstone SM, (2005) New antiviral pathway that mediates hepatitis C virus replicon interferon sensitivity through ADAR1. J Virol 79: 6291-8.
45. Lim SR, Qin X, Susser S, Nicholas JB, Lange C, et al. (2012) Virologic escape during danoprevir (ITMN-191/RG7227) monotherapy is hepatitis C virus subtype dependent and associated with R155K substitution. Antimicrob Agents Chemother 56: 271-9.
46. Adiwijaya BS, Herrmann E, Hare B, Kieffer T, Lin C, et al. (2010) A multi-variant, viral dynamic model of genotype 1 HCV to assess the in vivo evolution of protease-inhibitor resistant variants. PLoS Comput Biol 6: e1000745.
47. Adiwijaya BS, Kieffer TL, Henshaw J, Eisenhauer K, Kimko H, et al. (2012) A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection. PLoS Comput Biol 8: e1002339.
48. Rong L, Ribeiro RM, Perelson AS, (2012) Modeling quasispecies and drug resistance in hepatitis C patients treated with a protease inhibitor. Bull Math Biol 74: 1789-817.
49. Powers KA, Dixit NM, Ribeiro RM, Golia P, Talal AH, et al. (2003) Modeling viral and drug kinetics: hepatitis C virus treatment with pegylated interferon alfa-2b. Semin Liver Dis 23 (Suppl 1):: 13-8.
50. Talal AH, Ribeiro RM, Powers KA, Grace M, Cullen C, et al. (2006) Pharmacodynamics of PEG-IFN alpha differentiate HIV/HCV coinfected sustained virological responders from nonresponders. Hepatology 43: 943-53.
51. Dahari H, Affonso de Araujo ES, Haagmans BL, Layden TJ, Cotler SJ, et al. (2010) Pharmacodynamics of PEG-IFN-alpha-2a in HIV/HCV co-infected patients: Implications for treatment outcomes. J Hepatol 53: 460-7.
52. Guedj J, Dahari H, Pohl RT, Ferenci P, Perelson AS, (2012) Understanding silibinin's modes of action against HCV using viral kinetic modeling. J Hepatol 56: 1019-24.