Rational Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection

PLoS Computational Biology

Volumn 11, Issue 6, 2015, Pages

  Ke, Ruian ^a,g   Loverdo, Claude ^a,b   Qi, Hangfei ^c   Sun, Ren ^a,c,d,e   Lloyd Smith, James O ^a,f  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b SORBONNE UNIVERSITÉ   (France)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^e ZHEJIANG UNIVERSITY   (China)

^f NATIONAL INSTITUTES OF HEALTH   (United States)

^g LOS ALAMOS NATIONAL LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG THERAPY;

ADAPTIVE MANAGEMENT; ANTIVIRALS; COMBINATION THERAPY; DESIGN MANAGEMENT; DRUG-RESISTANCE; HEALTH CONCERNS; HEPATITIS C VIRUS; RATIONAL DESIGN; VIRUS INFECTION; VIRUS POPULATION;

VIRUSES;

ANTIVIRUS AGENT; ASUNAPREVIR; DACLATASVIR;

ANTIVIRAL RESISTANCE; ARTICLE; COMBINATION CHEMOTHERAPY; HEPATITIS C; HIGH RISK PATIENT; MEDICATION COMPLIANCE; MODEL; PHARMACODYNAMICS; PHARMACOKINETICS; PUBLIC HEALTH PROBLEM; RISK ASSESSMENT; TREATMENT OUTCOME; BIOLOGICAL MODEL; BIOLOGY; DRUG EFFECTS; GENETICS; HEPACIVIRUS; HUMAN; PHYSIOLOGY; REPRODUCTIVE FITNESS; VIROLOGY;

ANTIVIRAL AGENTS; COMPUTATIONAL BIOLOGY; DRUG RESISTANCE, VIRAL; GENETIC FITNESS; HEPACIVIRUS; HEPATITIS C; HUMANS; MEDICATION ADHERENCE; MODELS, BIOLOGICAL;

EID: 84941224725     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1004040     Document Type: Article

References (60)

1. Thomas DL, (2013) Global control of hepatitis C: where challenge meets opportunity. Nat Med 19: 850–858. doi: 10.1038/nm.3184 23836235
2. Lavanchy D, (2009) The global burden of hepatitis C. Liver Int 29 Suppl 1: 74–81. doi: 10.1111/j.1478-3231.2008.01934.x 19207969
3. Scheel TK, Rice CM, (2013) Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med 19: 837–849. doi: 10.1038/nm.3248 23836234
4. Gane E, (2011) Future hepatitis C virus treatment: interferon-sparing combinations. Liver Int 31 Suppl 1: 62–67. doi: 10.1111/j.1478-3231.2010.02383.x 21205140
5. Zeuzem S, Jacobson IM, Baykal T, Marinho RT, Poordad F, et al. (2014) Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 370: 1604–1614. doi: 10.1056/NEJMoa1401561 24720679
6. Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, et al. (2014) Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 370: 1879–1888. doi: 10.1056/NEJMoa1402355 24720702
7. Feld JJ, Kowdley KV, Coakley E, Sigal S, Nelson DR, et al. (2014) Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 370: 1594–1603. doi: 10.1056/NEJMoa1315722 24720703
8. Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, et al. (2014) Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 370: 1889–1898. doi: 10.1056/NEJMoa1402454 24725239
9. Pol S, Ghalib RH, Rustgi VK, Martorell C, Everson GT, et al. (2012) Daclatasvir for previously untreated chronic hepatitis C genotype-1 infection: a randomised, parallel-group, double-blind, placebo-controlled, dose-finding, phase 2a trial. Lancet Infect Dis 12: 671–677. doi: 10.1016/S1473-3099(12)70138-X 22714001
10. Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, et al. (2012) Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med 366: 216–224. doi: 10.1056/NEJMoa1104430 22256805
11. Qi H, Olson CA, Wu NC, Ke R, Loverdo C, et al. (2014) A quantitative high-resolution genetic profile rapidly identifies sequence determinants of hepatitis C viral fitness and drug sensitivity. PLoS Pathog 10: e1004064. doi: 10.1371/journal.ppat.1004064 24722365
12. Robinson M, Tian Y, Delaney WEt, Greenstein AE, (2011) Preexisting drug-resistance mutations reveal unique barriers to resistance for distinct antivirals. Proc Natl Acad Sci U S A 108: 10290–10295. doi: 10.1073/pnas.1101515108 21646519
13. Pawlotsky JM, (2011) Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology 53: 1742–1751. doi: 10.1002/hep.24262 21374691
14. Ribeiro RM, Li H, Wang S, Stoddard MB, Learn GH, et al. (2012) Quantifying the diversification of hepatitis C virus (HCV) during primary infection: estimates of the in vivo mutation rate. PLoS Pathog 8: e1002881. doi: 10.1371/journal.ppat.1002881 22927817
15. Powdrill MH, Tchesnokov EP, Kozak RA, Russell RS, Martin R, et al. (2011) Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance. Proc Natl Acad Sci U S A 108: 20509–20513. doi: 10.1073/pnas.1105797108 22135458
16. Simmonds P, (2004) Genetic diversity and evolution of hepatitis C virus—15 years on. J Gen Virol 85: 3173–3188. 15483230
17. Pybus OG, Charleston MA, Gupta S, Rambaut A, Holmes EC, et al. (2001) The epidemic behavior of the hepatitis C virus. Science 292: 2323–2325. 11423661
18. Lieveld FI, van Vlerken LG, Siersema PD, van Erpecum KJ, (2013) Patient adherence to antiviral treatment for chronic hepatitis B and C: a systematic review. Ann Hepatol 12: 380–391. 23619254
19. Lo Re V, 3rdTeal V, Localio AR, Amorosa VK, Kaplan DE, et al. (2011) Relationship between adherence to hepatitis C virus therapy and virologic outcomes: a cohort study. Ann Intern Med 155: 353–360. doi: 10.7326/0003-4819-155-6-201109200-00003 21930852
20. Sarrazin C, Zeuzem S, (2010) Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology 138: 447–462. doi: 10.1053/j.gastro.2009.11.055 20006612
21. Mathes T, Antoine SL, Pieper D, (2014) Factors influencing adherence in Hepatitis-C infected patients: a systematic review. Bmc Infectious Diseases 14.
22. Chung RT, Baumert TF, (2014) Curing chronic hepatitis C—the arc of a medical triumph. N Engl J Med 370: 1576–1578. doi: 10.1056/NEJMp1400986 24720678
23. Ford N, Singh K, Cooke GS, Mills EJ, von Schoen-Angerer T, et al. (2012) Expanding access to treatment for hepatitis C in resource-limited settings: lessons from HIV/AIDS. Clin Infect Dis 54: 1465–1472. doi: 10.1093/cid/cis227 22431808
24. Smith RJ, Okano JT, Kahn JS, Bodine EN, Blower S, (2010) Evolutionary dynamics of complex networks of HIV drug-resistant strains: the case of San Francisco. Science 327: 697–701. doi: 10.1126/science.1180556 20075214
25. Roberts RR, Hota B, Ahmad I, Scott RD, 2ndFoster SD, et al. (2009) Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin Infect Dis 49: 1175–1184. doi: 10.1086/605630 19739972
26. DiMasi JA, Hansen RW, Grabowski HG, (2003) The price of innovation: new estimates of drug development costs. J Health Econ 22: 151–185. 12606142
27. Bangsberg DR, Perry S, Charlebois ED, Clark RA, Roberston M, et al. (2001) Non-adherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS 15: 1181–1183. 11416722
28. Paterson DL, Swindells S, Mohr J, Brester M, Vergis EN, et al. (2000) Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 133: 21–30. 10877736
29. Gordon SC, Yoshida EM, Lawitz EJ, Bacon BR, Sulkowski MS, et al. (2013) Adherence to assigned dosing regimen and sustained virological response among chronic hepatitis C genotype 1 patients treated with boceprevir plus peginterferon alfa-2b/ribavirin. Aliment Pharmacol Ther 38: 16–27. doi: 10.1111/apt.12342 23710734
30. Evon DM, Esserman DA, Bonner JE, Rao T, Fried MW, et al. (2013) Adherence to PEG/ribavirin treatment for chronic hepatitis C: prevalence, patterns, and predictors of missed doses and nonpersistence. J Viral Hepat 20: 536–549. doi: 10.1111/jvh.12079 23808992
31. Weiss JJ, Brau N, Stivala A, Swan T, Fishbein D, (2009) Review article: adherence to medication for chronic hepatitis C—building on the model of human immunodeficiency virus antiretroviral adherence research. Aliment Pharmacol Ther 30: 14–27. doi: 10.1111/j.1365-2036.2009.04004.x 19416131
32. zur Wiesch PA, Kouyos R, Engelstadter J, Regoes RR, Bonhoeffer S, (2011) Population biological principles of drug-resistance evolution in infectious diseases. Lancet Infect Dis 11: 236–247. doi: 10.1016/S1473-3099(10)70264-4 21371657
33. Gelman MA, Glenn JS (2010) Mixing the right hepatitis C inhibitor cocktail. Trends Mol Med.
34. Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, et al. (2008) The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis 46: 155–164. doi: 10.1086/524891 18171244
35. Rosenbloom DI, Hill AL, Rabi SA, Siliciano RF, Nowak MA, (2012) Antiretroviral dynamics determines HIV evolution and predicts therapy outcome. Nat Med 18: 1378–1385. 22941277
36. Wahl LM, Nowak MA, (2000) Adherence and drug resistance: predictions for therapy outcome. Proc Biol Sci 267: 835–843. 10819155
37. Soriano V, Perelson AS, Zoulim F, (2008) Why are there different dynamics in the selection of drug resistance in HIV and hepatitis B and C viruses? J Antimicrob Chemother 62: 1–4. doi: 10.1093/jac/dkn175 18441341
38. Suzuki Y, Ikeda K, Suzuki F, Toyota J, Karino Y, et al. (2012) Dual Oral Therapy with Daclatasvir and Asunaprevir for Patients with HCV Genotype 1b Infection and Limited Treatment Options. J Hepatol.
39. Ribeiro RM, Bonhoeffer S, (2000) Production of resistant HIV mutants during antiretroviral therapy. Proc Natl Acad Sci U S A 97: 7681–7686. 10884399
40. Rong L, Dahari H, Ribeiro RM, Perelson AS, (2010) Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2: 30ra32. doi: 10.1126/scitranslmed.3000544 20445200
41. Loverdo C, Lloyd-Smith JO, (2013) Intergenerational phenotypic mixing in viral evolution. Evolution 67: 1815–1822. doi: 10.1111/evo.12048 23730772
42. Loverdo C, Park M, Schreiber SJ, Lloyd-Smith JO, (2012) Influence of viral replication mechanisms on within-host evolutionary dynamics. Evolution 66: 3462–3471. doi: 10.1111/j.1558-5646.2012.01687.x 23106710
43. Alexander HK, Bonhoeffer S, (2012) Pre-existence and emergence of drug resistance in a generalized model of intra-host viral dynamics. Epidemics 4: 187–202. doi: 10.1016/j.epidem.2012.10.001 23351371
44. Nordqvist O, Sodergard B, Tully MP, Sonnerborg A, Lindblad AK, (2006) Assessing and achieving readiness to initiate HIV medication. Patient Educ Couns 62: 21–30. 16766244
45. Kosaka K, Imamura M, Hayes CN, Abe H, Hiraga N, et al. (2014) Emergence of resistant variants detected by ultra-deep sequencing after asunaprevir and daclatasvir combination therapy in patients infected with hepatitis C virus genotype 1. J Viral Hepat.
46. Karino Y, Toyota J, Ikeda K, Suzuki F, Chayama K, et al. (2013) Characterization of virologic escape in hepatitis C virus genotype 1b patients treated with the direct-acting antivirals daclatasvir and asunaprevir. J Hepatol 58: 646–654. doi: 10.1016/j.jhep.2012.11.012 23178977
47. Ke R, Loverdo C, Qi H, Olson CA, Wu NC, et al. (2014) Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma concentration. J Antimicrob Chemother 69: 724–727. doi: 10.1093/jac/dkt423 24169581
48. Nettles RE, Gao M, Bifano M, Chung E, Persson A, et al. (2011) Multiple ascending dose study of BMS-790052, a nonstructural protein 5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1. Hepatology 54: 1956–1965. doi: 10.1002/hep.24609 21837752
49. Eley T, Pasquinelli C, Wendelburg P, Villegas C, He B, et al. (2010) Safety and Pharmacokinetics of BMS-650032 Following Multiple Ascending Doses for 14 Days in Healthy Subjects. ICAAC. Boston.
50. Fridell RA, Qiu D, Wang C, Valera L, Gao M, (2010) Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. Antimicrob Agents Chemother 54: 3641–3650. doi: 10.1128/AAC.00556-10 20585111
51. Fridell RA, Wang C, Sun JH, O'Boyle DR, 2ndNower P, et al. (2011) Genotypic and phenotypic analysis of variants resistant to hepatitis C virus nonstructural protein 5A replication complex inhibitor BMS-790052 in humans: in vitro and in vivo correlations. Hepatology 54: 1924–1935. doi: 10.1002/hep.24594 21809362
52. Xiao F, Fofana I, Thumann C, Mailly L, Alles R, et al. (2014) Synergy of entry inhibitors with direct-acting antivirals uncovers novel combinations for prevention and treatment of hepatitis C. Gut.
53. 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: 103–107. 9756471
54. Dahari H, Shteingart S, Gafanovich I, Cotler SJ, D'Amato M, et al. (2014) Sustained virological response with intravenous silibinin: individualized IFN-free therapy via real-time modelling of HCV kinetics. Liver Int.
55. Guedj J, Perelson AS, (2011) Second-phase hepatitis C virus RNA decline during telaprevir-based therapy increases with drug effectiveness: implications for treatment duration. Hepatology 53: 1801–1808. doi: 10.1002/hep.24272 21384401
56. 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: 706–713. doi: 10.1038/clpt.2010.35 20463660
57. Guedj J, Dahari H, Rong L, Sansone ND, Nettles RE, et al. (2013) 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 U S A 110: 3991–3996. doi: 10.1073/pnas.1203110110 23431163
58. Garg AX, Adhikari NK, McDonald H, Rosas-Arellano MP, Devereaux PJ, et al. (2005) Effects of computerized clinical decision support systems on practitioner performance and patient outcomes: a systematic review. JAMA 293: 1223–1238. 15755945
59. Perelson AS, Nelson PW, (1999) Mathematical analysis of HIV-1 dynamics in vivo. SIAM review 41: 42.
60. Ke R, Lloyd-Smith JO, (2012) Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors. PLoS Comput Biol 8: e1002744. doi: 10.1371/journal.pcbi.1002744 23133349