Modelling hepatitis C therapy-predicting effects of treatment

Nature Reviews Gastroenterology and Hepatology

Volumn 12, Issue 8, 2015, Pages 437-445

  Perelson, Alan S ^a   Guedj, Jeremie ^b  

^a LOS ALAMOS NATIONAL LABORATORY   (United States)

^b UNIVERSITÉ PARIS DIDEROT   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALISPORIVIR; ALPHA INTERFERON; ANTIVIRUS AGENT; BIOLOGICAL MARKER; CILUPREVIR; DACLATASVIR; DANOPREVIR; DIRECT ACTING ANTIVIRAL AGENT; INTERFERON; LEDIPASVIR; MERICITABINE; NONSTRUCTURAL PROTEIN 5A INHIBITOR; PEGINTERFERON; PROTEINASE INHIBITOR; RADALBUVIR; RIBAVIRIN; SOFOSBUVIR; SVR 12; TEGOBUVIR; TELAPREVIR; UNCLASSIFIED DRUG; VEDROPREVIR; VIRUS RNA;

CELLS; CLINICAL TRIAL (TOPIC); COMBINATION CHEMOTHERAPY; DOSE RESPONSE; DRUG EFFICACY; DRUG HALF LIFE; DYNAMICS; ERADICATION THERAPY; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; IMMUNE RESPONSE; IN VIVO STUDY; INFECTED CELL; KINETICS; LIMIT OF DETECTION; LIVER CIRRHOSIS; LIVER REGENERATION; MATHEMATICAL MODEL; MONOTHERAPY; PATHOGENESIS; PHASE 2 CLINICAL TRIAL (TOPIC); PREDICTION; PRIORITY JOURNAL; RELIABILITY; REVIEW; SINGLE DRUG DOSE; THERAPY EFFECT; TREATMENT DURATION; TREATMENT RESPONSE; VIRAL CLEARANCE; VIRION; VIRUS INHIBITION; VIRUS KINETICS; VIRUS LOAD; VIRUS REPLICATION; ANTIVIRAL RESISTANCE; BIOLOGICAL MODEL; COMBINATION DRUG THERAPY; DRUG EFFECTS; HEPATITIS C, CHRONIC; METABOLISM; PHYSIOLOGY; TIME FACTOR; TREATMENT OUTCOME;

ANTIVIRAL AGENTS; BIOMARKERS; DRUG RESISTANCE, VIRAL; DRUG THERAPY, COMBINATION; HEPATITIS C, CHRONIC; HUMANS; INTERFERON-ALPHA; LIVER REGENERATION; MODELS, BIOLOGICAL; RNA, VIRAL; TIME FACTORS; TREATMENT OUTCOME; VIRAL LOAD; VIRION;

EID: 84938751694     PISSN: 17595045     EISSN: 17595053     Source Type: Journal    
DOI: 10.1038/nrgastro.2015.97     Document Type: Review

References (94)

1. Gane E. J., et al. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS 9669 against HCV genotype 1 infection. Gastroenterology 146, 736-743 (2014
2. Ho D. D., et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV 1 infection. Nature 373, 123-126 (1995
3. Perelson A. S., et al. Decay characteristics of HIV 1 infected compartments during combination therapy. Nature 387, 188-191 (1997
4. Perelson A. S., Neumann A. U., Markowitz M., Leonard J. M., & Ho D. D. HIV 1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271, 1582-1586 (1996
5. Wei X., et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373, 117-122 (1995
6. Neumann A. U., et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 282, 103-107 (1998
7. Dahari H., Sainz B. Jr., Perelson A. S., & Uprichard S. L. Modeling subgenomic hepatitis C virus RNA kinetics during treatment with alpha interferon. J. Virol. 83, 6383-6390 (2009
8. Rong L., & Perelson A. S. Mathematical analysis of multiscale models for hepatitis C virus dynamics under therapy with direct-acting antiviral agents. Math. Biosci. 245, 22-30 (2013
9. Powers K. A., et al. Modeling viral and drug kinetics: hepatitis C virus treatment with pegylated interferon alfa-2b. Sem. Liver Dis. 23 (Suppl. 1), 13-18 (2003
10. Herrmann E., Lee J. H., Marinos G., Modi M., & Zeuzem S. Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon. Hepatology 37, 1351-1358 (2003
11. Dixit N. M., Layden-Almer J. E., Layden T. J., & Perelson A. S. Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature 432, 922-924 (2004
12. Pawlotsky J. M., et al. Antiviral action of ribavirin in chronic hepatitis C. Gastroenterology 126, 703-714 (2004
13. Talal A. H., et al. Pharmacodynamics of PEG-IFN alpha differentiate HIV/HCV coinfected sustained virological responders from nonresponders. Hepatology 43, 943-953 (2006
14. Herrmann E., et al. Viral kinetics in patients with chronic hepatitis C treated with the serine protease inhibitor BILN 2061. Antivir. Ther. 11, 371-376 (2006
15. Dahari H., Ribeiro R. M., & Perelson A. S. Triphasic decline of hepatitis C virus RNA during antiviral therapy. Hepatology 46, 16-21 (2007
16. Dahari H., Lo A., Ribeiro R. M., & Perelson A. S. Modeling hepatitis C virus dynamics: liver regeneration and critical drug efficacy. J. Theor. Biol. 247, 371-381 (2007
17. Reluga T. C., Dahari H., & Perelson A. S. Analysis of hepatitis C virus infection models with hepatocyte homeostasis. SIAM J. Appl. Math. 69, 999-1023 (2009
18. Dahari H., Shudo E., Cotler S. J., Layden T. J., & Perelson A. S. Modelling hepatitis C virus kinetics: the relationship between the infected cell loss rate and the final slope of viral decay. Antivir. Ther. 14, 459-464 (2009
19. Dahari H., et al. Pharmacodynamics of PEG IFN alpha-2a in HIV/HCV co-infected patients: implications for treatment outcomes. J. Hepatol. 53, 460-467 (2010
20. Dahari H., Rong L., Layden T. J., & Cotler S. J. Hepatocyte proliferation and hepatitis C virus kinetics during treatment. Clin. Pharmacol. Ther. 89, 353-354 (2011
21. Saltzman J., Nachbar R., Panochorchan P., Stone J., & Khan A. in 2009 SIAM Conference on Mathematics for Industry (eds Fields D. A., & Peters T. J.) 73-83 (Society for Industrial and Applied Mathematics, 2010
22. Reddy M. B., et al. Pharmacokinetic/pharmacodynamic predictors of clinical potency for hepatitis C virus nonnucleoside polymerase and protease inhibitors. Antimicrob. Agents Chemother. 56, 3144-3156 (2012
23. Nguyen T. H. T., Mentré F., Yu J., Levi M., & Guedj J. A pharmacokinetic-viral kinetic model describes the effect of alisporivir monotherapy or in combination with peg-IFN on hepatitis C virologic response. Clin. Pharm. Ther. 96, 599-608 (2014
24. Nguyen T. H. T., & Guedj J. HCV kinetic models and their implication in drug development. CPT Pharmacometrics Syst. Pharmacol. 4, 231-242 (2015
25. Dixit N. M., & Perelson A. S. The metabolism, pharmacokinetics and mechanisms of antiviral activity of ribavirin against hepatitis C virus. Cell. Mol. Life Sci. 63, 832-842 (2006
26. Feld J. J. Is there a role for ribavirin in the era of hepatitis C virus direct-acting antivirals?. Gastroenterology 142, 1356-1359 (2012
27. Feld J. J., et al. Ribavirin improves early responses to peginterferon through improved interferon signaling. Gastroenterology 139, 154-162 (2010
28. Rotman Y., et al. Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C. Gut 63, 161-169 (2014
29. Thomas E., et al. Ribavirin potentiates interferon action by augmenting interferon-stimulated gene induction in hepatitis C virus cell culture models. Hepatology 53, 32-41 (2011
30. Mihm U., Herrmann E., Sarrazin C., & Zeuzem S. Review article: predicting response in hepatitis C virus therapy. Aliment. Pharmacol. Ther. 23, 1043-1054 (2006
31. Canini L., et al. A pharmacokinetic/viral kinetic model to evaluate the treatment effectiveness of danoprevir against chronic HCV. Antivir. Ther. http://dx.doi.org/10.3851/IMP2879
32. Shudo E., Ribeiro R. M., Talal A. H., & Perelson A. S. A hepatitis C viral kinetic model that allows for time-varying drug effectiveness. Antivir. Ther. 13, 919-926 (2008
33. Conway J. M., & Perelson A. S. A hepatitis C virus infection model with time-varying drug effectiveness: solution and analysis. PLoS Comp. Biol. 10, e1003769 (2014
34. Shudo E., Ribeiro R. M., & Perelson A. S. Modeling hepatitis C virus kinetics under therapy using pharmacokinetic and pharmacodynamic information. Expert Opin. Drug Metab. Toxicol. 5, 321-332 (2009
35. Guedj J., & Perelson A. S. Second-phase hepatitis C virus RNA decline during telaprevir-based therapy increases with drug effectiveness: implications for treatment duration. Hepatology 53, 1801-1808 (2011
36. Guedj J., Dahari H., Shudo E., Smith P., & Perelson A. S. Hepatitis C viral kinetics with the nucleoside polymerase inhibitor mericitabine (RG7128). Hepatology 55, 1030-1037 (2012
37. Guedj J., et al. Analysis of the hepatitis C viral kinetics during administration of two nucleotide analogues: sofosbuvir (GS 7977) and GS 0938. Antivir. Ther. 19, 211-220 (2014
38. Canini L., et al. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy. Antivir. Ther. 20, 149-155 (2014
39. Canini L., & Perelson A. S. Viral kinetic modeling: state of the art. J. Pharmacokinet. Pharmacodyn. 41, 431-433 (2014
40. Gao M., et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 465, 96-100 (2010
41. Adiwijaya B. S., et al. Rapid decrease of wild-type hepatitis C virus on telaprevir treatment. Antivir. Ther. 14, 591-595 (2009
42. Guedj J., Dahari H., Shudo E., Smith P., & Perelson A. S. Hepatitis C viral kinetics with the nucleoside polymerase inhibitor mericitabine (RG7128). Hepatology 55, 1030-1037(2012
43. Guedj J., et al. 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 110, 3991-3996 (2013
44. Neumann A. U., et al. Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus. J. Infect. Dis. 182, 28-35 (2000
45. Rong L., et al. Analysis of hepatitis C virus decline during treatment with the protease inhibitor danoprevir using a multiscale model. PLoS Comp. Biol. 9, e1002959 (2013
46. McGivern D. R., et al. Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors. Gastroenterology 147, 453-462 (2014
47. McGivern D. R., et al. Protease inhibitors block multiple functions of the NS3/4A protease-helicase during the hepatitis C virus life cycle. J. Virol. 89, 5362-5370 (2015
48. Meredith L. W., Farquhar M. J., Tarr A. W., & McKeating J. A. Type I interferon rapidly restricts infectious hepatitis C virus particle genesis. Hepatology 60, 1891-1901 (2014
49. Dahari H., Ribeiro R. M., Rice C. M., & Perelson A. S. Mathematical modeling of subgenomic hepatitis C virus replication in Huh 7 cells. J. Virol. 81, 750-760 (2007
50. Binder M., et al. Replication vesicles are load-and choke-points in the hepatitis C virus lifecycle. PLoS Pathog. 9, e1003561 (2013
51. Snoeck E., et al. A comprehensive hepatitis C viral kinetic model explaining cure. Clin. Pharmacol. Ther. 87, 706-713 (2010
52. Reesink H. W., et al. Rapid HCV-RNA decline with once daily TMC435: a phase I study in healthy volunteers and hepatitis C patients. Gastroenterology 138, 913-921 (2010
53. Blight K. J., McKeating J. A., & Rice C. M. Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. J. Virol. 76, 13001-13014 (2002
54. Robinson M., et al. Novel hepatitis C virus reporter replicon cell lines enable efficient antiviral screening against genotype 1a. Antimicrob. Agents Chemother. 54, 3099-3106 (2010
55. Farley S. A double whammy for hep C. Nat. Rev. Drug Discov. 2, 419 (2003
56. Liang Y., et al. Antiviral suppression vs restoration of RIG I signaling by hepatitis C protease and polymerase inhibitors. Gastroenterology 135, 1710-1718 (2008
57. Osinusi A., et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA 310, 804-811 (2013
58. Guedj J., & Neumann A. U. 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, 330-340 (2010
59. Laouenan C., et al. 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. Antimicrob. Agents Chemother. 58, 5332-5341 (2014
60. Centro V., et al. Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice. Digestive Liver Dis. 47, 233-241 (2015
61. Kohli A., et al. Virologic response after 6 week triple-drug regimes for hepatitis C: a proof of concept phase 2A cohort study. Lancet 385, 1107-1113 (2015
62. Sarrazin C., et al. Importance of very early HCV RNA kinetics for prediction of treatment outcome of highly effective all oral direct-acting antiviral combination therapy. J. Virol. Methods 214, 29-32 (2015
63. Gane E. J., et al. 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. Lancet 376, 1467-1475 (2010
64. Gane E. J., et al. Mericitabine and ritonavir-boosted danoprevir with or without ribavirin in treatment-naive HCV genotype 1 patients: INFORM-SVR study. Liver Intl 35, 79-89 (2015
65. Kowdley K. V., et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N. Engl. J. Med. 370, 1879-1888 (2014
66. Sulkowski M., et al. 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. Lancet 385, 1087-1097 (2014
67. Colombatto P., et al. 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. Clin. Pharmacol. Ther. 84, 212-215 (2008
68. Adiwijaya B. S., et al. A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection. PLoS Comp. Biol. 8, e1002339 (2012
69. Guedj J., et al. Modeling viral kinetics and treatment outcome during alisporivir interferon-free treatment in HCV genotype 2/3 patients. Hepatology 59, 1706-1714 (2014
70. Kieffer T. L., et al. Telaprevir and pegylated interferon alpha 2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients. Hepatology 46, 631-639 (2007
71. Adiwijaya B. S., et al. A multi-variant, viral dynamic model of genotype 1 HCV to assess the in vivo evolution of protease-inhibitor resistant variants. PLoS Comp. Biol. 6, e1000745 (2010
72. Ribeiro R. M., et al. Quantifying the diversification of hepatitis C virus (HCV) during primary infection: estimates of the in vivo mutation rate. PLoS Pathog. 8, e1002881 (2012
73. Cuevas J. M., González-Candelas F., Moya A., & Sanjuán R. Effect of ribavirin on the mutation rate and spectrum of hepatitis C virus in vivo. J. Virol. 83, 5760-5764 (2009
74. Rong L., Dahari H., Ribeiro R. M., & Perelson A. S. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci. Trans. Med. 2, 30ra32 (2010
75. Haseltine E. L., et al. Modeling viral evolutionary dynamics after telaprevir-based treatment. PLoS Comp. Biol. 10, e1003772 (2014
76. Rong L., Ribeiro R. M., & Perelson A. S. Modeling quasispecies and drug resistance in hepatitis C patients treated with a protease inhibitor. Bull. Math. Biol. 74, 1789-1817 (2012
77. Schaller T., et al. Analysis of hepatitis C virus superinfection exclusion by using novel fluorochrome gene-tagged viral genomes. J. Virol. 81, 4591-4603 (2007
78. Tscherne D. M., et al. Superinfection exclusion in cells infected with hepatitis C virus. J. Virol. 81, 3693-3703 (2007
79. Webster B., Ott M., & Greene W. C. Evasion of superinfection exclusion and elimination of primary viral RNA by an adapted strain of hepatitis C virus. J. Virol. 87, 13354-13369 (2013
80. Hedskog C., et al. Characterization of hepatitis C virus intergenotypic recombinant strains and associated virological response to sofosbuvir/ribavirin. Hepatology 61, 471-480 (2015
81. Pawelek K. A., et al. Modeling within-host dynamics of influenza virus infection including immune responses. PLoS Comp. Biol. 8, e1002588 (2012
82. Greco W. R., Bravo G., & Parsons J. C. The search for synergy: a critical review from a response surface perspective. Pharmacol. Rev. 47, 331-385 (1995
83. Lee J. J., Kong M., Ayers G. D., & Lotan R. Interaction index and different methods for determining drug interaction in combination therapy. J. Biopharm. Stat. 17, 461-480 (2007
84. Cheng G., et al. Antiviral activity and resistance profile of the novel HCV NS5A inhibitor GS 5885. J. Hepatol. 56, S464 (2012
85. Sidharthan S., et al. Utility of hepatitis C viral load monitoring on directly acting antiviral therapy. Clin. Infect. Dis. 60, 1743-1751 (2015
86. Saez-Cirion A., et al. Post-treatment HIV 1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 9, e1003211 (2013
87. Conway J. M., & Perelson A. S. Post-treatment control of HIV infection. Proc. Natl. Acad Sci. USA 112, 5467-5472 (2015
88. Shimizu Y. K., Purcell R. H., & Yoshikura H. Correlation between the infectivity of hepatitis C virus in vivo and its infectivity in vitro. Proc. Natl Acad. Sci. USA 90, 6037-6041 (1993
89. Lawitz E., et al. 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. J. Hepatol 59, 18-23 (2013
90. Soriano V., et al. Very late relapse after discontinuation of antiviral therapy for chronic hepatitis C. Antiviral therapy 18, 1033-1035 (2013
91. Barreiro P., et al. Very late HCV relapse following triple therapy for hepatitis C. Antivir. Ther. 19, 723-724 (2014
92. Veerapu N. S., Raghuraman S., Liang T. J., Heller T., & Rehermann B. Sporadic reappearance of minute amounts of hepatitis C virus RNA after successful therapy stimulates cellular immune responses. Gastroenterology 140, 676-685 (2011
93. Lin J. C., et al. Interferon γ induced protein 10 kinetics in treatment-naive versus treatment-experienced patients receiving interferon-free therapy for hepatitis C virus infection: Implications for the innate immune response. J. Infect. Dis. 10, 1881-1885 (2014
94. Food and Drug Administration Center for Drug Evaluation Research. Guidance for industry chronic Hepatitis C virus infection: developing direct-acting antiviral drugs for treatment [online], http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm225333.pdf (2013