Telaprevir: A Hepatitis C NS3/4A Protease Inhibitor

Clinical Therapeutics

Volumn 34, Issue 9, 2012, Pages 1857-1882

  Matthews, Samuel James ^a   Lancaster, Jason W ^a  

^a NORTHEASTERN UNIVERSITY   (United States)

Author keywords

Anemia; Hepatitis C genotype 1; Rash; Telaprevir

Indexed keywords

ALFUZOSIN; ATAZANAVIR PLUS RITONAVIR; ATORVASTATIN; CISAPRIDE; DARUNAVIR; EFAVIRENZ; EMTRICITABINE; FOSAMPRENAVIR; LOPINAVIR; MEVINOLIN; MIDAZOLAM; PEGINTERFERON; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; PIMOZIDE; RIBAVIRIN; SILDENAFIL; SIMVASTATIN; TADALAFIL; TELAPREVIR; TENOFOVIR; TRIAZOLAM;

ABDOMINAL PAIN; ANEMIA; ANOREXIA; ANTIVIRAL SUSCEPTIBILITY; ASTHENIA; CHOLELITHIASIS; COST EFFECTIVENESS ANALYSIS; DEPRESSION; DIZZINESS; DRESS SYNDROME; DRUG ABSORPTION; DRUG BINDING; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG ERUPTION; DRUG MECHANISM; DRUG METABOLISM; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; ECZEMA; ERYTHEMA; ERYTHEMA MULTIFORME; FATIGUE; FEVER; FLU LIKE SYNDROME; GASTROINTESTINAL DISEASE; HEADACHE; HEMOLYTIC ANEMIA; HEPATITIS C; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INNATE IMMUNITY; INSOMNIA; JAUNDICE; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; MALAISE; MIXED INFECTION; NAUSEA; NEUTROPENIA; NONHUMAN; PHARMACOGENOMICS; PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN STRUCTURE; PRURITUS; RACE DIFFERENCE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RELAPSE; REVIEW; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; STEVENS JOHNSON SYNDROME; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; URIC ACID BLOOD LEVEL; VIRUS LOAD; VIRUS REPLICATION; VOMITING;

ANTIVIRAL AGENTS; DRUG APPROVAL; DRUG THERAPY, COMBINATION; GENOTYPE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; OLIGOPEPTIDES; PROTEASE INHIBITORS; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 84866184057     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2012.07.011     Document Type: Review

References (97)

1. Incivek (telaprevir) [package insert] 2012, Vertex Pharmaceuticals, Cambridge, Mass.
2. Victrelis (boceprevir) [package insert] 2011, Merck & Co, Whitehouse Station, NJ.
3. Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 2011, 17:107-115.
4. Kershenobich D., Razavi H.A., Cooper C.L., et al. Applying a system approach to forecast the total hepatitis C virus-infected population size: model validation using US data. Liver Int 2011, 31(Suppl 2):4-17.
5. Thein H.-H., Yi Q., Dore G.J., et al. Estimation of stage-specific fibrosis progression rates in chronic hepatiis C virus infection: a meta-analysis and meta-regression. Hepatol 2008, 48:418-431.
6. Takehara T., Hayashi N. Innate immunity in type C hepatitis. Hepatitis C Virus Disease: Immunobiology and Clinical Applications 2008, 1-15. Springer Science and Business Media, New York, NY. E. Jirillo (Ed.).
7. Ly K.N., Xing J., Klevens R.M., et al. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med 2012, 156:271-278.
8. EASL clinical practice guidelines: management of hepatitis C virus infection. J Hepatol 2011, 55:245-264.
9. Manns M.P., McHutchison J.G., Gordon S.C., et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 2001, 358:958-965.
10. Fried M.W., Shiffman M.L., Reddy K.R., et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002, 347:975-982.
11. Hadziyannis S.J., Sette H., Morgan T.R., et al. Peginterferon alpha 2a and ribavirin combination therapy in chronic hepatitis C: A randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004, 140:346-355.
12. Zeuzem S., Hultcrantz R., Bourlier M., et al. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol 2004, 40:993-999.
13. Khuroo M.S., Khuroo M.S., Dahab S.T. Meta-analysis: A randomized trial of peginterferon plus ribavirin for the initial treatment of chronic hepatitis C genotype 4. Aliment Pharmacol Ther 2004, 20:931-938.
14. Hasan F., Asker H., Al-Khaldi J., et al. Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4. Am J Gastroenterol 2004, 99:1733-1737.
15. Kamal S.M., El Tawil A.A., Nakano T., et al. Peginterferon α-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response. Gut 2005, 54:858-866.
16. D'Heygere F., George C., Van Vlierberghe H., et al. Efficacy of interferon-based antiviral therapy in patients with chronic hepatitis C infected with genotype 5: a meta-analysis of two large prospective clinical trials. J Med Virol 2011, 83:815-819.
17. Bonny C., Fontaine H., Poynard T., et al. Effectiveness of interferon plus ribavirin combination in the treatment of naïve patients with hepatitis C virus type 5. A French multicentre retrospective study. Aliment Pharmacol Ther 2006, 24:593-600.
18. Fung J., Lai C.-L., Hung I., et al. Chronic hepatitis C virus genotype 6 infection: response to pegylated interferon and ribavirin. J Infect Dis 2008, 198:808-812.
19. Nguyen N.H., VuTien P., Garcia R.T., et al. Response to pegylated interferon and ribavirin in Asian American patients with chronic hepatitis C genotypes 1 vs 2/3 vs 6. J Viral Hepat 2010, 17:691-697.
20. Foster G.R., Hézode C., Bronowicki J.-P., et al. Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not genotype 3 infections. Gastroenterology 2011, 141:881-889.
21. Benhamou Y., Moussalli J., Ratziu V., et al. Activity of telaprevir monotherapy or in combination with peginterferon-alfa-2a and ribavirin in treatment-naïve genotype 4 hepatitis-C patients: final results of study C210. Hepatology 2010, 52(Suppl):719A-720A. Abstract 828.
22. Dash S., Hazari S., Garry R.F., et al. Mechanisms of interferon action and resistance in chronic hepatitis C virus infection: lessons learned from cell culture studies. Hepatitis C Virus Disease: Immunobiology and Clinical Applications 2008, 16-38. Springer Science and Business Media, New York, NY. E. Jirillo (Ed.).
23. Perni R.B., Almquist S.J., Byrn R.A., et al. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother 2006, 50:899-909.
24. Geitmann M., Dahl G., Danielson U.H. Mechanistic and kinetic characterization of hepatitis C virus NS3 protein interactions with NS4A and protease inhibitors. J Mol Recognit 2011, 24:60-70.
25. Rosen H.R. Chronic hepatitis C infection. N Engl J Med 2011, 364:2429-2438.
26. Li K., Foy E., Ferreon J.C., et al. 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 2005, 102:2992-2997.
27. Meylan E., Curran J., Hofmann K., et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by the hepatitis C virus. Nature 2005, 437:1167-1172.
28. Foy E., Li K., Wang C., et al. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 2003, 300:1145-1148.
29. Horner S.M., Gale M. Intracellular innate immune cascades and interferon defenses that control hepatitis C virus. J Interferon Cytokine Res 2009, 29:489-498.
30. Vermehren J., Sarrazin C. New hepatitis C therapies in clinical development. Eur J Med Res 2011, 16:303-314.
31. Lok A.S., Gardiner D.F., Lawitz E., et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med 2012, 366:216-224.
32. Kuntzen T., Timm J., Berical A., et al. Naturally occurring dominant resistance mutations in HCV protease and polymerase inhibitors in treatment-naïve patients. Hepatology 2008, 48:1769-1778.
33. Sarrazin C., Kieffer T.L., Bartels D., et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 2007, 132:1767-1777.
34. Kieffer T.L., Sarrazin C., Miller J.S., et al. Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients. Hepatology 2007, 46:631-639.
35. Jacobson I.M., McHutchison J.G., Dusheiko G., et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011, 364:2405-2416.
36. Zeuzem S., Andreone P., Pol S., et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011, 364:2417-2428.
37. Sherman K.E., Flamm S.L., Afdhal N.H., et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med 2011, 365:1014-1024.
38. Susser S., Vermehren J., Forestier N., et al. Analysis of long-term persistence of resistance mutations within the hepatitis C virus NS3 protease after treatment with telaprevir or boceprevir. J Clin Virol 2011, 52:321-327.
39. Zeuzem S., Sulkowski M.S., Zoulim F., et al. Long-term follow-up of patients with chronic hepatitis C treated with telaprevir in combination with peginterferon alfa-2a and ribavirin: interim analysis of the EXTEND study. Hepatology 2010, 52(Suppl):436A. Abstract 227.
40. De Meyer S., Dierynck I., Ghys A., et al. Characterization of HCV variants in non-SVR patients in the REALIZE study suggests that telaprevir exhibits a consistent resistance profile irrespective of a lean-in Accessed April 6, 2012. http://www1.easl.eu/easl2011/program/Posters/Abstract1080.htm.
41. Forestier N., Reesink H.W., Weegink C.J., et al. Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C. Hepatol 2007, 46:640-648.
42. Suzuki F., Akuta N., Suzuki Y., et al. Rapid loss of hepatitis C virus genotype 1b from serum in patients receiving a triple treatment with telaprevir (MP-424), pegylated interferon and ribavirin for 12 weeks. Hepatol Res 2009, 39:1056-1063.
43. Garg V, Luo X, McNair L, et al. The effect of low-dose ritonavir on the pharmacokinetics of the investigational HCV protease inhibitor telaprevir in healthy volunteers. Presented at: 18th Conference on Retroviruses and Opportunistic Infections (CROI), Boston, Mass, February 27-March 3, 2011. Abstract 629.
44. van Heeswijk R, Gysen V, Boogaerts G, The pharmacokinetic interaction between tenofovir disoproxil fumarate and the investigational HCV protease inhibitor telaprevir. Presented at: 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/46th Annual Meeting of the Infectious Diseases Society of America (IDSA), Washington, DC, October 25-28, 2008. Abstract A-966.
45. Marcellin P., Forns X., Goeser T., et al. Telaprevir is effective given every 8 or 12 hours with ribavirin and peginterferon alfa-2a or -2b to patients with chronic hepatitis C. Gastroenterology 2011, 140:459-468.
46. Lawitz E., Rodriguez-Torres M., Muir A.J., et al. Antiviral effects and safety of telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C patients. J Hepatol 2008, 49:163-169.
47. Telaprevir briefing document April 28, 2011 US Food and Drug Administration, Antiviral Drugs Advisory Committee, Accessed June 6, 2012. http://www.fda.gov/downloads/Advisory-Committees/Committees/MeetingMaterials/Drugs/AntiviralDrugsAdvisory-Committee/UCM252562.pdf.
48. van Heeswijk R., Boogaerts G., De Paepe E., et al. The effect of different types of food on the bioavailability of the investigational HCV protease inhibitor telaprevir. Rev Antiviral Ther Infect Dis 2011, 6:21. Abstract 19.
49. Garg V., Chandorkar G., Smith F., et al. Effect of telaprevir on the pharmacokinetics of midazolam and digoxin. Rev Antiviral Ther Infect Dis 2011, 6:14. Abstract 12.
50. Chakilam A., Chavan A., Smith G., et al. Telaprevir binding to isolated human plasma proteins and protein binding displacement interactions between telaprevir and ritonavir or warfarin. Rev Antiviral Ther Infect Dis 2011, 6:22. Abstract 20.
51. Lin K., Perni R.B., Kwong A.D., et al. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells. Antimicrob Agents Chemother 2006, 50:1813-1822.
52. Chakilam A., Chavan A., Smith G., et al. A validated HPLC-MS/MS assay method for the determination of telaprevir and its R-diastereomer in human plasma. Rev Antiviral Ther Infect Dis 2011, 6:12. Abstract 10.
53. van Heeswijk R., Vandevoorde A., Boogaerts G., et al. The effect of severe renal impairment on the pharmacokinetics of the investigational HCV protease inhibitor Telaprevir Accessed April 7, 2012. http://www1.easl.eu/easl2011/program/Posters/Abstract1123.htm.
54. Adiwijaya B., Chandorkar G., van Heeswijk R., et al. Effect of mild and moderate hepatic impairment on telaprevir pharmacokinetics. Rev Antiviral Ther Infect Dis 2011, 6:3. Abstract 1.
55. Garg V., Chandorkar G., Yang Y., et al. The effect of CYP3A inhibitors and inducers on the pharmacokinetics of telaprevir. Rev Antiviral Ther Infect Dis 2011, 6:15. Abstract 13.
56. Lee J.E., van Heeswijk R., Alves K., et al. Effect of the hepatitis c virus protease inhibitor telaprevir on the pharmacokinetics of amlodipine and atorvastatin. Antimicrob Agents Chemother 2011, 55:4569-4574.
57. Garg V., Yang Y., Smith F., et al. The pharmacokinetics interaction between an oral contraceptive containing ethinyl estradiol and norethindrone and telaprevir. Rev Antiviral Ther Infect Dis 2011, 6:19. Abstract 17.
58. McHutchison J.G., Everson G.T., Gordon S.C., et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009, 360:1827-1838.
59. Hézode C., Forestier N., Dusheiko G., et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009, 360:1839-1850.
60. McHutchison J.G., Manns M.P., Muir A.J., et al. Telaprevir for previously treated chronic HCV infection. N Engl J Med 2010, 362:1292-1303.
61. Kumada H., Toyota J., Okanoue T., et al. Telaprevir with peginterferon and ribavirin for treatment-naïve patients chronically infected with HCV of genotype 1 in Japan. J Hepatol 2012, 56:78-84.
62. Hayashi N., Okanoue T., Tsubouchi H., et al. Efficacy and safety of telaprevir, a new protease inhibitor, for difficult-to-treat patients with genotype 1 chronic hepatitis C. J Viral Hepatol 2012, 19:e134-e142.
63. Staples C.T., Rimland D., Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival. Clin Infect Dis 1999, 29:150-154.
64. Sherman K.E., Rouster S.D., Chung R.T., et al. Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the U.S. adult AIDS clinical trials group. Clin Infect Dis 2002, 34:831-873.
65. Sulkowski M.S., Moore R.D., Mehta S.H., et al. Hepatitis C and progression of HIV disease. JAMA 2002, 288:199-206.
66. Cachafeiro S.P., Del Amo J., Iribarren J.A., et al. Decrease in serial prevalence of coinfection with hepatitis C virus among HIV-infected patients in Spain, 1977-2006. Clin Infect Dis 2009, 48:1467-1470.
67. Soriano V., Puoti M., Sulkowski M., et al. Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV-HIV international panel. AIDS 2007, 21:1073-1089.
68. Torriani F.J., Rodriguez-Torres M., Rockstroh J.K., et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004, 351:438-450.
69. Chung R.T., Andersen J., Volberding P., et al. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med 2004, 351:451-459.
70. Laguno M., Murillas J., Blanco J.L., et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS 2004, 18:F27-F36.
71. Carrat F., Bani-Sadr F., Pol S., et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA 2004, 292:2839-2848.
72. Núñez M., Miralles C., Berdún M.A., et al. Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses 2007, 23:972-982.
73. Dieterich D, Soriano V, Sherman K, et al. Telaprevir in combination with pegylated interferon-α-2a + RBV in HCV/HIV-co-infected patients: a 24-week treatment interim analysis. Presented at: 19th Conference on Retroviruses and Opportunistic Infections. Seattle, Washington, March 5-8, 2012. Abstract 46.
74. Van Heeswijk R., Vandevoorde A., Boogaerts G., et al. Pharmacokinetic interactions between ARV agents and the investigational HCV protease inhibitor TVR in healthy volunteers Accessed April 7, 2012. http://www.retroconference.org/2011/Abstracts/41437.htm.
75. Dierynck I, De Meyer S, Kieffer T, et al. Evaluation of telaprevir and HIV-1 protease inhibitors in 2-drug combination studies against HIV-1 activity. Presented at: 19th Conference on Retroviruses and Opportunistic Infections. Seattle, Washington, March 5-8, 2012. Abstract 756.
76. Van Heeswijk, R, Garg V, Boogaerts G, et al. The pharmacokinetic interaction between telaprevir and raltegravir in healthy volunteers. Presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011). Chicago, September 17-20, 2011. Abstract A1-1738a.
77. Bani-Sadr F., Carrat F., Pol S., et al. Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy. J Acquir Immune Defic Syndr 2005, 40:47-52.
78. Nunez M., Ocampo A., Aguirrebengoa K., et al. Incidence of anaemia and impact on sustained virological response in HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin. J Viral Hepat 2008, 15:363-369.
79. Thompson A.J., Muir A.J., Sulkowski M.S., et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterol 2010, 139:120-129.
80. Chayama K., Hayes C.N., Abe H., et al. IL28B but not ITPA polymorphism is predictive of response to pegylated interferon, ribavirin and telaprevir triple therapy in patients with genotype 1 hepatitis C. J Infect Dis 2011, 204:84-93.
81. Aparicio E., Parera M., Franco S., et al. IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients. PLoS One 2010, 5:e13771.
82. de Castellarnau M., Aparicio E., Parera M., et al. Deciphering the interleukin 28B variants that better predict response to pegylated interferon-α and ribavirin therapy in HCV/HIV-1 coinfected patients. PLoS One 2012, 7:e31016.
83. Fellay J., Thompson A.J., Ge D., et al. ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature 2010, 464:405-408.
84. Jacobson IM, Catlett I, Marcellin P, et al. Telaprevir substantially improved SVR rates across all IL28B genotypes in the ADVANCE trial. Presented at: 46th Annual Meeting of the European Association for the Study of the Liver. Berlin, Germany, March 30-April 3, 2011. Abstract 904.
85. Younossi Z.M., Aerssens J., Pol S., et al. Similar SVR rates in IL28B CC, CT or TT prior relapser, partial- or null-responder patients treated with telaprevir/peginterferon/ribavirin: retrospective analysis of the REALIZE study. Gastroenterology 2011, (5 Suppl 1):S907-S908.
86. Ghany M.G., Nelson D.R., Strader D.B., et al. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guidelines by the American Association for the Study of Liver Disease. Hepatology 2011, 54:1433-1444.
87. Matthews S.J., McCoy Pegylated interferons: clinical applications in the management of hepatitis C infection. Hepatitis C Virus Disease. Immunobiology and Clinical Applications 2008, 237-296. Springer Science and Business Media, New York, NY. E. Jirillo (Ed.).
88. Poordad F., Sulkowski M., Reddy R., et al. Anemia had no effect on efficacy outcomes in treatment-naïve patient who received telaprevir-based regimen in the ADVANCE and ILLUMINATE phase 3 studies. Gastroenterol 2011, 140(5 Suppl 1):S898-S899.
89. Montaudié H., Passeron T., Cardot-Leccia N., et al. Drug rash with eosinophilia and systemic symptoms due to telaprevir. Dermatology 2010, 221:303-305.
90. Dupin N., Mallet V., Carlotti A., et al. Severe skin rash in case of re-administration of telaprevir in a patient who previously experienced a non severe rash. Hepatology 2012, 55:2042-2043.
91. Gellad Z.F., Naggie S., Reed S.D., et al. The cost-effectiveness of a telaprevir-inclusive regimen as initial therapy for genotype 1 hepatitis C infection in individuals with the CC IL28B polymorphism. Hepatology 2011, 54(Suppl 4):417A-418A. Abstract 118.
92. Liu S., Cipriano L.E., Holodniy M., et al. New protease inhibitors for the treatment of chronic hepatitis C. A cost-effectiveness analysis. Ann Intern Med 2012, 156:279-290.
93. Chan K., Lai M., Groessl E.J., et al. Long term clinical impact of direct antiviral agent (DAA) therapy for untreated chronic hepatitis C genotype 1 infection in the Veterans Health Administration. Hepatology 2011, 54(4 Suppl):437A. Abstract 158.
94. Pegasys (peginterferon alfa) [package insert] 2011, Hoffman-LaRoche Inc, Nutley, NJ.
95. Peg-Intron (ribavirin) [package insert] 2011, Schering Corp, Kenilworth,NJ.
96. Harrington P.R., Zeng W., Naeger L.K. Clinical relevance of detectable but not quantifiable hepatitis C virus RNA during boceprevir or telaprevir treatment. Hepatology 2012, 55:1048-1057.
97. A 2-part, open label study of telaprevir in combination with peginterferon alfa-2a (Pegasys) and ribavirin (Copegus) in subjects chronically infected with genotype 1 hepatitis C virus following liver transplantation ClinicalTrials.gov Identifier NCT01467505, Accessed April 1, 2012. http://clinicaltrials.gov/ct2/show/NCT01467505.