New antiviral therapies in the management of HCV infection

Antiviral Therapy

Volumn 17, Issue 5, 2012, Pages 771-783

  Farnik, Harald ^a   Zeuzem, Stefan ^a  

^a UNIVERSITY HOSPITAL FRANKFURT   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2' DEOXY 2' FLUORO 2' METHYLCYTIDINE; ALBINTERFERON ALPHA2B; ALISPORIVIR; ASUNAPREVIR; BALAPIRAVIR; BOCEPREVIR; CILUPREVIR; CYCLOSPORIN; DACLATASVIR; DANOPREVIR; FALDAPREVIR; MERICITABINE; N (2' DEOXY 2' FLUORO 2' METHYL P PHENYL 5' URIDYLYL)ALANINE ISOPROPYL ESTER; NARLAPREVIR; NESBUVIR; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; PEGINTERFERON LAMBDA; PLACEBO; RAPAMYCIN; RECOMBINANT ALPHA2B INTERFERON; RIBAVIRIN; RITONAVIR; SETROBUVIR; SIMEPREVIR; TACROLIMUS; TARIBAVIRIN; TEGOBUVIR; TELAPREVIR; UNINDEXED DRUG;

ANEMIA; ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; BILIRUBIN BLOOD LEVEL; BLOOD TOXICITY; BLOOD TRANSFUSION; CARDIOTOXICITY; COMBINATION CHEMOTHERAPY; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG POTENTIATION; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ECZEMA; FLU LIKE SYNDROME; GASTROINTESTINAL SYMPTOM; GENOTYPE; HEMATOLOGIC DISEASE; HEPATITIS C; HUMAN; LIVER CIRRHOSIS; MONOTHERAPY; MUSCULOSKELETAL DISEASE; NAUSEA; NONHUMAN; PRIORITY JOURNAL; PRURITUS; RELAPSE; REVIEW; SIDE EFFECT; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; VIRUS INHIBITION; VIRUS LOAD;

ANTIVIRAL AGENTS; DRUG RESISTANCE, VIRAL; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84865726171     PISSN: 13596535     EISSN: None     Source Type: Journal    
DOI: 10.3851/IMP2127     Document Type: Review

References (89)

1. Hnatyszyn HJ. Chronic hepatitis C and genotyping: the clinical significance of determining HCV genotypes. Antivir Ther 2005; 10:1-11.
2. Poynard T, Yuen MF, Ratziu V, et al. Viral hepatitis C. Lancet 2003; 362:2095-2100.
3. Veldt BJ, Heathcote EJ, Wedemeyer H, et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med 2007; 147:677-684.
4. Niederau C, Lange S, Heintges T, et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology 1998; 28:1687-1695.
5. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347:975-982.
6. Hadziyannis SJ, Sette H, Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004; 140:346-355.
7. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358:958-965.
8. Farnik H, Lange CM, Sarrazin C, Kronenberger B, Zeuzem S, Herrmann E. Meta-analysis shows extended therapy improves response of patients with chronic hepatitis C virus genotype 1 infection. Clin Gastroenterol Hepatol 2010; 8:884-890.
9. Kim JL, Morgenstern KA, Lin C, et al. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 1996; 87:343-355.
10. Lohmann V, Korner F, Koch J, Herian U, Theilmann L, Bartenschlager R. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 1999; 285:110-113.
11. Moradpour D, Penin F, Rice CM. Replication of hepatitis C virus. Nat Rev Microbiol 2007; 5:453-463.
12. Wakita T, Pietschmann T, Kato T, et al. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 2005; 11:791-796.
13. Sarrazin C, Zeuzem S. Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology 2010; 138:447-462.
14. Sarrazin C, Kieffer TL, 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.
15. Lamarre D, Anderson PC, Bailey M, et al. An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature 2003; 426:186-189.
16. Hinrichsen H, Benhamou Y, Wedemeyer H, et al. Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis c genotype 1 patients. Gastroenterology 2004; 127:1347-1355.
17. Forestier N, Reesink HW, Weegink CJ, et al. Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C. Hepatology 2007; 46:640-648.
18. Reesink HW, Zeuzem S, Weegink CJ, et al. Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a Phase 1b, placebo-controlled, randomized study. Gastroenterology 2006; 131:997-1002.
19. Kieffer TL, Sarrazin C, Miller JS, 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.
20. 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.
21. McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; 360:1827-1838.
22. McHutchison JG, Manns MP, Muir AJ, et al. Telaprevir for previously treated chronic HCV infection. N Engl J Med 2010; 362:1292-1303.
23. 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.
24. Benhamou Y, Moussalli J, Ratziu V, et al. Activity of telaprevir monotherapy or in combination with peginterferon alfa 2a and ribavirin in treatment-naive genotype 4 hepatitis C patients: final results of study C210. Hepatology 2010; 52:719A.
25. Foster GR, Hezode C, Bronowicki JP, 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.
26. Jacobson IM, McHutchinson JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011; 364:2405-2416.
27. Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364:2417-2428.
28. Sherman KE, Flamm SL, Afdhal NH, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med 2011; 365:1014-1024.
29. Sarrazin C, Rouzier R, Wagner F, et al. SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders. Gastroenterology 2007; 132:1270-1278.
30. Kwo PY, Lawitz EJ, McCone J, et al. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre Phase 2 trial. Lancet 2010; 376:705-716.
31. Poordad F, McCone J, Jr., Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364:1195-1206.
32. Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011; 364:1207-1217.
33. Muir AJ, Bonstein JD, Killenberg PG, et al. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in Blacks and non-Hispanic Whites. N Engl J Med 2004; 350:2265-2271.
34. Sulkowski MS, Bourliere M, Bronowicki JP, et al. SILEN-C2 Sustained virologic response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in chronic HCV genotype-1 patients with non-response to PO/R. J Hepatol 2011; 54 Suppl 1:S30.
35. Manns MP, Bourlière M, Benhamou Y, et al. Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. J Hepatol 2011; 54:1114-1122.
36. Zeuzem S, Asselah T, Angus P, et al. Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection. Gastroenterology 2011; 141:2047-2055.
37. Sulkowski MS, Ceasu E, Asselah T, et al. SILEN-C1: sustained virologic response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naive patients with chronic genotype 1 HCV infection. J Hepatol 2011; 54 Suppl 1:S27.
38. de Bruijne J, Bergmann JF, Reesink HW, et al. Antiviral activity of narlaprevir combined with ritonavir and pegylated interferon in chronic hepatitis C patients. Hepatology 2010; 52:1590-1599.
39. Detishin V, Haazen W, Hooijmaijers X, et al. Final results of the pharmacokinetics, efficacy and safety/tolerability of 400 and 600 MG once daily dosing of ACH-1625 (HCV NS3 protease inhibitor) in HCV genotype 1. J Hepatol 2011; 54 Suppl 1:S186.
40. Forestier N, Larrey D, Guyader D, et al. 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 2011; 54:1130-1136.
41. Rouzier R, Larrey D, Gane EJ, et al. Activity of danoprevir plus low-dose ritonavir (DNV/R) in combination with peginterferon alfa 2a (40kd) plus ribavirin in previous null responders. J Hepatol 2011; 54 Suppl 1:S28.
42. Fried MW, Buti M, Dore GJ, Ferenci P. Efficacy and safety of TMC435 in combination with peginterferon alfa-2a and ribavirin in treatment-naive genotype-1 HCV patients: 24-week interim results from the PILLAR study. Hepatology 2010; 52:403A.
43. Zeuzem S, Foster GR, Fried MW, et al. The Aspire trial: TMC435 in treatment-experienced patients with genotype-1 HCV infection who have failed previous PEGIFN/RBV treatment. J Hepatol 2011; 54 Suppl 1:S546.
44. Corsa A, Robinson M, Yang H, et al. Preclinical properties of the novel HCV NS3 protease inhibitor GS-9451. J Hepatol 2011; 54 Suppl 1:S313.
45. Halfen P, Courcambeck J, Whitaker T, et al. GNS-227: a new potent and selective HCV NS3 protease inhibitor with high genetic barrier to resistance. J Hepatol 2011; 54 Suppl 1:S478.
46. Larrey D, Carenco C, Guyader D, et al. High sustained virological response (SVR) rate after danoprevir for only 14 days associated with PEG-interferon alfa-2a and ribavirin in treatment-naive chronic HCV genotype 1 patients. J Hepatol 2011; 54 Suppl 1:S481.
47. Pockros PJ, Nelson D, Godofsky E, et al. R1626 plus peginterferon alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin. Hepatology 2008; 48:385-397.
48. Roberts SK, Cooksley G, Dore GJ, et al. Robust antiviral activity of R1626, a novel nucleoside analogue: a randomized, placebo-controlled study in patients with chronic hepatitis C. Hepatology 2008; 48:398-406.
49. Pockros P, Jensen D, Tsai N, et al. First SVR data with the nucleoside analogue polymerase inhibitor mericitabine (RG7128) combined with peginterferon/ribavirin in treatment-naive HCV G1/4 patients: interim analysis from the JUMP-C trial. J Hepatol 2011; 54 Suppl 1:S538.
50. Lalezari J, Lawitz E, Rodriguez-Torres M, et al. Once daily PSI-7977 plus PEGIFN/RBV in a Phase 2b trial: rapid virologic suppresion in treatment-naive patients with HCV GT2/3. J Hepatol 2011; 54 Suppl 1:S28.
51. Lawitz E, Rodriguez-Torres M, Denning J, et al. Once daily dual-nucleotide combination of PSI-938 and PSI-7977 provides 94% HCV RNA
52. Nelson DR, Lalezari J, Lawitz E, et al. Once daily PSI-7977 plus PEG-IFN/RBV in HCV GT1: 98% rapid virological response, complete early virologic response: the proton study. J Hepatol 2011; 54 Suppl 1:S544.
53. Rodriguez-Torres M, Lawitz E, Denning J, et al. PSI-352938, a novel, purine nucleotide analog, exhibits potent antiviral activity and no evidence of resistance in patients with HCV genotype 1 over 7 days. J Hepatol 2011; 54 Suppl 1:S488.
54. Larrey D, Lohse AW, de Ledinghen V, et al. Rapid and strong antiviral activity of the non-nucleosidic NS5B polymerase inhibitor BI 207127 in combination with peginterferon alfa 2a and ribavirin. J Hepatol 2012; in press.
55. Kukolj G, Anderson PC, Boes M, et al. Preclinical characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941. J Hepatol 2011; 54 Suppl 1:S480.
56. Erhardt A, Deterding K, Benhamou Y, et al. Safety, pharmacokinetics and antiviral effect of BILB 1941, a novel hepatitis C virus RNA polymerase inhibitor, after 5 days oral treatment. Antivir Ther 2009; 14:23-32.
57. Wagner F, Thompson R, Kantaridis C, et al. Antiviral activity of the hepatitis C virus polymerase inhibitor filibuvir in genotype 1-infected patients. Hepatology 2011; 54:50-59.
58. Cooper C, Lawitz EJ, Ghali P, et al. Evaluation of VCH-759 monotherapy in hepatitis C infection. J Hepatol 2009; 51:39-46.
59. Lawitz E, Cooper C, Rodriguez-Torres M, et al. Safety, tolerability and antiviral activity of VCH-916, a novel non-nucleoside HCV polymerase inhibitor in patients with chronic HCV genotype 1 infection. J Hepatol 2009; 50 Suppl 1:S37.
60. Di Bisceglie AM, Nelson DR, Gane E, et al. VX-222 with TVR alone or in combination with PEG-interferon alfa-2a and ribavirin in treatment-naive patients with chronic hepatitis: Zenith study interim results. J Hepatol 2011; 54 Suppl 1:S540.
61. Lawitz E, Rodriguez-Torres M, Rustgi VK, et al. Safety and antiviral activity of ANA598 in combination with pegylated inteferon alfa-2a plus ribavirin in treatment-naive genotype-1 chronic HCV patients. Hepatology 2010; 52 Suppl 1:334A.
62. Rodriguez-Torres M, Lawitz E, Cohen D, et al. Treatment-naive, HCV genotype 1-infected subjects shoe sinificantly greater HCV RNA decreases when treated with 28 days of ABT-333 plus peginterferon and ribavirin compared to peginterferon and ribavirin alone. Hepatology 2009; 50:5A.
63. Kneteman NM, Howe AY, Gao T, et al. HCV796: a selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus. Hepatology 2009; 49:745-752.
64. Pockros PJ, Rodriguez-Torres M, Villano S, et al. A Phase 2, randomized study of HCV-796 in combination with pegylated-interferon (PEG) plus ribavirin (RBV) versus PEG plus RBV in hepatitis C virus genotype-1 infection. J Hepatol 2009; 50 Suppl 1:S7.
65. Lawitz E, Jacobson I, Godofsky E, et al. A Phase 2b trial comparing 24 to 48 weeks treatment with tegobuvir (GS-9190)/PEG/RBV to 48 weeks treatment with tegobuvir (GS-9190)/PEG/RBV to 48 weeks treatment with PEG/RBV for chronic genotype 1 HCV infection. J Hepatol 2011; 54 Suppl 1:S181.
66. Hebner C, Harris J, Oldach D, et al. Emergence and persistence of NS5B mutations following combination treatment with tegobuvir (GS-9190) plus standard of carelong-term folow-up from the Phase IIb study GS-US-196-0103. J Hepatol 2011; 54 Suppl 1:S478.
67. Zeuzem S, Buggisch P, Agarwal K, et al. The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C. Hepatology 2012; 55:749-758.
68. de Bruijne J, van de Wetering de Rooij J, van Vliet AA, Leempoels J. Phase I study in healthy volunteers and patients with IDX375, a novel non-nucleoside HCV polymerase inhibitor. Hepatology 2010; 52:1219A.
69. Pol S, Everson GT, Ghalib R, Rustgi VK. Once-daily NS5A inhibitor (BMS-790052) plus peginterferon-alpha-2a and ribavirin produces high rates of extended rapid virologic response in treatment-naive HCV-genotype 1 subjects: Phase 2a trial. J Hepatol 2010; 52 Suppl 1:S462.
70. Pol S, Ghalib RH, Rustgi VK, et al. First report of SVR12 for a NS5A replication complex inhibitor, BMS-790052 in combination with PEG-IFNalfa-2a and RBV: Phase 2a trial in treatment-naive HCV-genotype-1 subjects. J Hepatol 2011; 54 Suppl 1:S544.
71. Colonno R, Huang N, Huang Q, et al. Characterization and identification of PPI-437, PPI-668 and PPI-833 as potent and selective HCV NS5A inhibitors with activity against all HCV genotypes. J Hepatol 2011; 54 Suppl 1:S474.
72. Gane EJ, Foster GR, Cianciara J, et al. Antiviral activity, pharmacokinetics and tolerability of AZD7295, a novel NS5A inhibitor, in a placebo-controlled multiple ascending dose study in HCV genotype 1 and 3 patients. J Hepatol 2010; 52 Suppl 1:S464.
73. Nettles R, Wang X, Quadri S, et al. BMS-824393 is a potent hepatitis c virus NS5A inibitor with substantial antiviral activity when given as monotherapy in subjects with chronic G1 HCV infection. Hepatology 2010; 52:1203A.
74. Gane EJ, Roberts SK, Stedman CA, 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 2010; 376:1467-1475.
75. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med 2012; 366:216-224.
76. Flisiak R, Horban A, Gallay P, et al. The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology 2008; 47:817-826.
77. Flisiak R, Pawlotsky JM, Crabbe R, et al. Once daily alisporivir (DEB025) plus PEGIFNalfa2a/Ribavirin results in superior sustained virologic response (SVR24) in chronic hepatitis C genotype 1 treatment naive patients. J Hepatol 2011; 54 Suppl 1:S2.
78. Hopkins S, Mosier S, Harris R, Kowalczyk P. Resistance selection following 15 days of monotherapy with SCY-635 a non-immunosuppressive cyclophilin inhibitor with potent anti-HCV activity. J Hepatol 2010; 52 Suppl 1:S15.
79. Gazák R, Walterova D, Kren V. Silybin and silymarin - new and emerging applications in medicine. Curr Med Chem 2007; 14:315-338.
80. Ahmed-Belkacem A, Ahnou N, Barbotte L, et al. Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase. Gastroenterology 2010; 138:1112-1122.
81. Ferenci P, Scherzer TM, Kerschner H, et al. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology 2008; 135:1561-1567.
82. Benhamou Y, Afdhal NH, Nelson DR, et al. A Phase III study of the safety and efficacy of viramidine versus ribavirin in treatment-naive patients with chronic hepatitis C: ViSER1 results. Hepatology 2009; 50:717-726.
83. Marcellin P, Gish RG, Gitlin N, et al. Safety and efficacy of viramidine versus ribavirin in ViSER2: randomized, double-blind study in therapy-naive hepatitis C patients. J Hepatol 2010; 52:32-38.
84. Poordad F, Lawitz E, Shiffman ML, et al. Virologic response rates of weight-based taribavirin versus ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C. Hepatology 2010; 52:1208-1215.
85. Nelson DR, Benhamou Y, Chuang WL, et al. Albinterferon Alfa-2b was not inferior to pegylated interferon-alpha in a randomized trial of patients with chronic hepatitis C virus genotype 2 or 3. Gastroenterology 2010; 139:1267-1276.
86. Zeuzem S, Sulkowski MS, Lawitz EJ, et al. Albinterferon Alfa-2b was not inferior to pegylated interferon-alpha in a randomized trial of patients with chronic hepatitis C virus genotype 1. Gastroenterology 2010; 139:1257-1266.
87. Long WA, Takov D, Tchernev K, et al. Q2week controlled-release- interferon-alpha2b plus ribavirin reduces flu-like symptoms >50% and provides equivalent efficacy in comparison to weekly pegylated-interferon-alpha2b plus ribavirin in treatment-naive-genotype 1 chronic hepatits C: results from EMPOWER, a randomized open label 12 week comparison in 133 patients. J Hepatol 2010; 52 Suppl 1:S467.
88. Zeuzem S, Arora S, Bacon B, et al. Pegylated interferon-lambda shows superior viral response with improved safety and tolerability versus PEGIFNalfa-2a in HCV patients (G1/2/3/4): emerge Phase 2b through week 12. J Hepatol 2011; 54 Suppl 1:S538.
89. Seden K, Back D, Khoo S. New directly acting antivirals for hepatitis C: potential for interaction with antiretrovirals. J Antimicrob Chemother 2010; 65:1079-1085.