Hepatitis C virus resistance to the new direct-acting antivirals

Expert Opinion on Drug Metabolism and Toxicology

Volumn 12, Issue 10, 2016, Pages 1197-1209

  Esposito, Isabella ^a   Trinks, Julieta ^b,c   Soriano, Vicente ^a  

^a HOSPITAL UNIVERSITARIO LA PAZ   (Spain)

^b Instituto Universitario del Hospital Italiano   (Argentina)

^c Universidad Nacional de Río Cuarto Consejo Nacional de Investigaciones Científicas y Técnicas   (Argentina)

Author keywords

Drug resistance; HCV; NS5A inhibitors; resistance testing; simeprevir; sofosbuvir

Indexed keywords

ANTIVIRUS AGENT; ASUNAPREVIR; DACLATASVIR; DASABUVIR; ELBASVIR PLUS GRAZOPREVIR; GLECAPREVIR; LEDIPASVIR; NONSTRUCTURAL PROTEIN 3; NONSTRUCTURAL PROTEIN 4A; NONSTRUCTURAL PROTEIN 5A INHIBITOR; OMBITASVIR; PARITAPREVIR; PIBRENTASVIR; PROTEINASE INHIBITOR; RNA DIRECTED RNA POLYMERASE INHIBITOR; RNA POLYMERASE; SIMEPREVIR; SOFOSBUVIR; SOFOSBUVIR PLUS VELPATASVIR; VANIPREVIR; VOXILAPREVIR;

ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; DRUG TREATMENT FAILURE; GENETIC VARIABILITY; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; NONHUMAN; REVIEW; VIRUS TRANSMISSION; DRUG EFFECTS; GENETICS; HEPACIVIRUS; HEPATITIS C, CHRONIC; ISOLATION AND PURIFICATION; TREATMENT FAILURE; VIROLOGY; VIRUS REPLICATION;

ANTIVIRAL AGENTS; DRUG RESISTANCE, VIRAL; HEPACIVIRUS; HEPATITIS C; HEPATITIS C, CHRONIC; HUMANS; TREATMENT FAILURE; VIRUS REPLICATION;

EID: 84987825073     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1080/17425255.2016.1209484     Document Type: Review

References (100)

1. A.M.Di Bisceglie Natural history of hepatitis C:its impact on clinical management. Hepatology. 2000;31:1014–1018.
2. E.Gower, C.Estes, S.Blach, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61(1):S45–S57.
3. A.H.Yau, E.M.Yoshida. Hepatitis C drugs:the end of the pegylated interferon era and the emergence of all-oral interferon-free antiviral regimens:a concise review. Can J Gastroenterol Hepatol. 2014;28:445–451.
4. T.Asselah, N.Boyer, D.Saadoun, et al. Direct-acting antivirals for the treatment of hepatitis C virus infection:optimizing current IFN-free treatment and future perspectives. Liver Int. 2016;36(Suppl 1):47–57.•• This review summarizes the most relevant results obtained with oral DAA combinations that have been approved and/or have completed phase III clinical trials for HCV infection.
5. C.Sarrazin. The importance of resistance to direct antiviral drugs in HCV infection in clinical practice. J Hepatol. 2016;64:486–504.• This is a comprehensive, systematic review of all resistance information for conventional triple therapies with sofosbuvir, simeprevir, and daclatasvir and available interferon-free DAA combinations.
6. L.Cuypers, G.Li, P.Libin, et al. Genetic diversity and selective pressure in hepatitis C virus genotypes 1–6:significance for direct-acting antiviral treatment and drug resistance. Viruses. 2015;7:5018–5039.
7. R.Schinazi, P.Halfon, P.Marcellin, et al. HCV direct-acting antiviral agents:the best interferon-free combinations. Liver Int. 2014;34(Suppl 1):69–78.
8. D.B.Smith, J.Bukh, C.Kuiken, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes:updated criteria and genotype assignment web resource. Hepatology. 2014;59:318–327.
9. E.Domingo, J.Sheldon, C.Perales. Viral quasispecies evolution. Microbiol Mol Biol Rev. 2012 Jun;76(2):159–216.
10. J.-M.Pawlotsky. Hepatitis:HCV variability, the immune system and resistance to antiviral drugs. Nat Rev Gastroenterol Hepatol. 2009;6:383–385.
11. J.-M.Pawlotsky. Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology. 2011;53:1742–1751.
12. J.Á.Patiño-Galindo, K.Salvatierra, F.González-Candelas, et al. Comprehensive screening for naturally occurring HCV resistance to direct-acting antivirals in the NS3, NS5A, and NS5B genes in worldwide isolates of viral genotypes 1 to 6. Antimicrob Agents Chemother. 2016;60:2402–2416.• This study comprehensively describes the natural HCV variation and polymorphism in all the three targets of approved DAAs (NS3, 99 NS5A, and NS5B) including all viral genotypes.
13. C.Welsch. Genetic barrier and variant fitness in hepatitis C as critical parameters for drug resistance development. Drug Discov Today Technol. 2014;11:19–25.
14. O.Lenz, T.Verbinnen, T.I.Lin, et al. In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435. Antimicrob Agents Chemother. 2010;54:1878–1887.
15. I.M.Jacobson, G.J.Dore, G.R.Foster, et al. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1):a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2014;384:403–413.
16. M.Manns, P.Marcellin, F.Poordad, et al. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2):a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2014;384:414–426.
17. S.Paolucci, L.Fiorina, A.Piralla, et al. Naturally occurring mutations to HCV protease inhibitors in treatment-naïve patients. Virol J. 2012;9:245.
18. E.Lawitz, M.S.Sulkowski, R.Ghalib, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients:the COSMOS randomised study. Lancet. 2014;384:1756–1765.
19. P.Kwo, N.Gitlin, R.Nahass, et al. Simeprevir plus sofosbuvir (12 and 8 weeks) in HCV genotype 1-infected patients without cirrhosis:OPTIMIST-1, a phase 3, randomized study. Hepatology. 2016 Jan 22. doi:10.1002/hep.28467.
20. E.Lawitz, G.Matusow, E.DeJesus, et al. Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis:a phase 3 study (OPTIMIST-2). Hepatology. 2015 Dec 24. doi:10.1002/hep.28422.
21. F.McPhee, J.Friborg, S.Levine, et al. Resistance analysis of the hepatitis C virus NS3 protease inhibitor asunaprevir. Antimicrob Agents Chemother. 2012;56:3670–3681.
22. M.Manns, S.Pol, I.M.Jacobson, et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b:a multinational, phase 3, multicohort study. Lancet. 2014;384:1597–1605.
23. K.Kosaka, M.Imamura, C.N.Hayes, et al. 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. 2015;22:158–165.
24. S.Yoshimi, M.Imamura, E.Murakami, et al. Long term persistence of NS5A inhibitor-resistant hepatitis C virus in patients who failed daclatasvir and asunaprevir therapy. J Med Virol. 2015;87:1913–1920.
25. T.Pilot-Matias, R.Tripathi, D.Cohen, et al. In vitro and in vivo antiviral activity and resistance profile of the hepatitis C virus NS3/4A protease inhibitor ABT-450. Antimicrob Agents Chemother. 2015;59:988–997.
26. P.Krishnan, R.Tripathi, G.Schnell, et al. Resistance analysis of baseline and treatment-emergent variants in hepatitis C virus genotype 1 in the AVIATOR study with paritaprevir-ritonavir, ombitasvir, and dasabuvir. Antimicrob Agents Chemother. 2015;59:5445–5454.
27. J.J.Feld, K.V.Kowdley, E.Coakley, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1594–1603.
28. S.Zeuzem, I.M.Jacobson, T.Baykal, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1604–1614.
29. E.Lawitz, M.Sulkowski, I.Jacobson, et al. Characterization of vaniprevir, a hepatitis C virus NS3/4A protease inhibitor, in patients with HCV genotype 1 infection:safety, antiviral activity, resistance, and pharmacokinetics. Antiviral Res. 2013;99:214–220.
30. R.J.Barnard, C.M.McHale, W.Newhard, et al. Emergence of resistance-associated variants after failed triple therapy with vaniprevir in treatment- experienced non-cirrhotic patients with hepatitis C-genotype 1 infection:a population and clonal analysis. Virology. 2013;443:278–284.
31. V.Soriano, E.Vispo, C.de Mendoza, et al. Hepatitis C therapy with HCV NS5B polymerase inhibitors. Expert Opin Pharmacother. 2013;14:1161–1170.
32. E.S.Svarovskaia, H.Dvory-Sobol, N.Parkin, et al. Infrequent development of resistance in genotype 1–6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials. Clin Infect Dis. 2014;59:1666–1674.
33. E.J.Gane, C.A.Stedman, R.H.Hyland, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013;368:34–44.
34. A.Osinusi, E.G.Meissner, Y.-J.Lee, et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics:a randomized clinical trial. Jama. 2013;310:804–811.
35. E.Lawitz, S.Flamm, J.Yang, et al. Retreatment of patients who failed 8 or 12 weeks of ledipasvir/sofosbuvir-based regimens with ledipasvir/sofosbuvir for 24 weeks. J Hepatol. 2015;62(Suppl. 1):S192.
36. E.F.Donaldson, P.R.Harrington, J.J.O’Rear, et al. Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir. Hepatology. 2015;61:56–65.
37. W.Kati, G.Koev, M.Irvin, et al. In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother. 2015;59:1505–1511.
38. R.A.Fridell, C.Wang, J.-H.Sun, et al. 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. 2011;54:1924–1935.
39. C.Wang, L.Jia, D.R.O’Boyle, et al. Comparison of daclatasvir resistance barriers on NS5A from hepatitis C virus genotypes 1 to 6:implications for cross-genotype activity. Antimicrob Agents Chemother. 2014;58:5155–5163.
40. H.Kumada, Y.Suzuki, K.Ikeda, et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology. 2014;59:2083–2091.
41. M.S.Sulkowski, D.F.Gardiner, M.Rodriguez-Torres, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370:211–221.
42. G.Cheng, B.Peng, A.Corsa, et al. Antiviral activity and resistance profile of the novel HCV NS5A inhibitor GS-5885. J Hepatol. 2012;56(Suppl 2):S464.
43. K.A.Wong, A.Worth, R.Martin, et al. Characterization of hepatitis C virus resistance from a multiple-dose clinical trial of the novel NS5A inhibitor GS-5885. Antimicrob Agents Chemother. 2013;57:6333–6340.
44. E.Lawitz, F.F.Poordad, P.S.Pang, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR):an open-label, randomised, phase 2 trial. Lancet. 2014;383:515–523.
45. N.Afdhal, S.Zeuzem, P.Kwo, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370:1889–1898.
46. N.Afdhal, K.R.Reddy, D.R.Nelson, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370:1483–1493.
47. P.Krishnan, J.Beyer, N.Mistry, et al. In vitro and in vivo antiviral activity and resistance profile of ombitasvir, an inhibitor of hepatitis C virus NS5A. Antimicrob Agents Chemother. 2015;59:979–987.
48. S.Zeuzem, R.Ghalib, K.R.Reddy, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection:a randomized trial. Ann Intern Med. 2015;163(1):1–13.
49. X.Forns, S.C.Gordon, E.Zuckerman, et al. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct acting antiviral agent. J Hepatol. 2015;63:564–572.
50. M.Sulkowski, C.Hezode, J.Gerstoft, 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 coinfection (C-WORTHY):a randomised, open-label phase 2 trial. Lancet. 2015;385:1087–1097.
51. J.J.Feld, I.M.Jacobson, C.Hézode, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373:2599–2607.
52. G.R.Foster, N.Afdhal, S.K.Roberts, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015;373:2608–2617.
53. E.J.Gane, C.Schwabe, R.H.Hyland, et al. Efficacy of the combination of sofosbuvir, velpatasvir, and the NS3/4A protease inhibitor GS-9857 in treatment-naïve or previously treated patients with HCV genotype 1 or 3 infections. Gastroenterology. 2016 May 27. pii:S0016-5085(16)34513-9.
54. E.J.Lawitz, W.D.O’Riordan, A.Asatryan, et al. Potent antiviral activities of the direct-acting antivirals ABT-493 and ABT-530 with three-day monotherapy for hepatitis C virus genotype 1 infection. Antimicrob Agents Chemother. 2016;60(3):1546–1555.
55. Z.Plaza, V.Soriano, E.Vispo, et al. Prevalence of natural polymorphisms at the HCV NS5A gene associated with resistance to daclatasvir, an NS5A inhibitor. Antivir Ther. 2012;17:921–926.
56. D.J.Bartels, J.C.Sullivan, E.Z.Zhang, et al. Hepatitis C virus variants with decreased sensitivity to direct-acting antivirals (DAAs) were rarely observed in DAA-naive patients prior to treatment. J Virol. 2013;87:1544–1553.
57. V.C.Di Maio, V.Cento, C.Mirabelli, et al. Hepatitis C virus genetic variability and the presence of NS5B resistance-associated mutations as natural polymorphisms in selected genotypes could affect the response to NS5B inhibitors. Antimicrob Agents Chemother. 2014;58:2781–2797.
58. C.Sarrazin, C.Hézode, S.Zeuzem, et al. Antiviral strategies in hepatitis C virus infection. J Hepatol. 2012;56(Suppl 1):S88–S100.
59. J.-M.Pawlotsky. New hepatitis C virus (HCV) drugs and the hope for a cure:concepts in anti-HCV drug development. Semin Liver Dis. 2014;34:22–29.
60. C.Sarrazin, H.Dvory-Sobol, E.S.Svarovskaia, et al. Baseline and post-baseline resistance analyses of phase 2/3 studies of ledipasvir/sofosbuvir +/_ RBV. Hepatology. 2014;60:1128a–1128a.
61. D.Finzi, J.Blankson, J.D.Siliciano, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med. 1999;5:512–517.
62. S.Margeridon-Thermet, E.S.Svarovskaia, F.Babrzadeh, et al. Low-level persistence of drug resistance mutations in hepatitis B virus-infected subjects with a past history of Lamivudine treatment. Antimicrob Agents Chemother. 2013;57:343–349.
63. J.Vermehren, S.Susser, C.M.Lange, et al. Mutations selected in the hepatitis C virus NS3 protease domain during sequential treatment with boceprevir with and without pegylated interferon alfa-2b. J Viral Hepat. 2012;19:120–127.
64. O.Lenz, J.de Bruijne, L.Vijgen, et al. Efficacy of re-treatment with TMC435 as combination therapy in hepatitis C virus-infected patients following TMC435 monotherapy. Gastroenterology. 2012;143:1176–1178.
65. S.Susser, M.Flinders, H.W.Reesink, et al. Evolution of hepatitis C virus quasispecies during repeated treatment with the NS3/4A protease inhibitor telaprevir. Antimicrob Agents Chemother. 2015;59:2746–2755.
66. S.Susser, J.Vermehren, N.Forestier, 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.
67. S.Paolucci, L.Fiorina, B.Mariani, et al. Development and persistence of DAA resistance associated mutations in patients failing HCV treatment. J Clin Virol. 2015;72:114–118.
68. S.Mohamed, M.Bourliere, S.Benali, et al. Clinical relevance of the HCV protease inhibitor-resistant mutant viral load assessed by ultra-deep pyrosequencing in treatment failure. J Clin Virol. 2016;78:36–43.
69. F.McPhee, D.Hernandez, F.Yu, et al. Resistance analysis of hepatitis C virus genotype 1 prior treatment null responders receiving daclatasvir and asunaprevir. Hepatology. 2013;58:902–911.
70. H.Dvory-Sobol, D.Wyles, W.Ouyang, et al. Long-term persistence of HCV NS5A variants after treatment with NS5A inhibitor ledipasvir. J Hepatol. 2015;62:S221.
71. P.Krishnan, R.Tripathi, G.Schnell, et al. Long-term follow-up of treatment-emergent resistance-associated variants in NS3, NS5A and NS5B with paritaprevir/r, ombitasvir and dasabuvir-based regimens. J Hepatol. 2015;62:S213–S234.
72. J.C.Sullivan, S.De Meyer, D.J.Bartels, et al. Evolution of treatment-emergent resistant variants in telaprevir phase 3 clinical trials. Clin Infect Dis. 2013;57:221–229.
73. R.J.Barnard, J.A.Howe, R.A.Ogert, et al. Analysis of boceprevir resistance associated amino acid variants (RAVs) in two phase 3 boceprevir clinical studies. Virology. 2013;444:329–336.
74. P.Krishnan, R.Tripathi, G.Schnell, et al. Pooled analysis of resistance in patients treated with ombitasvir/ABT-450/r and dasabuvir with or without ribavirin in phase 2 and phase 3 clinical trials. Hepatology. 2014;60:1134a–1135a.
75. O.Lenz, T.Verbinnen, B.Fevery, et al. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in phase IIb/III studies. J Hepatol. 2015;62:1008–1014.
76. J.Dietz, S.Susser, C.Berkowski, et al. Consideration of viral resistance for optimization of direct antiviral therapy of hepatitis C virus genotype 1-infected patients. PLoS One. 2015;10:e0134395.
77. S.Franco, C.Tural, M.Nevot, et al. Detection of a sexually transmitted hepatitis C virus protease inhibitor-resistance variant in a human immunodeficiency virus-infected homosexual man. Gastroenterology. 2014;147:599–601.
78. D.J.Bartels, Y.Zhou, E.Z.Zhang, et al. Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3/4A protease inhibitors in treatment-naive subjects. J Infect Dis. 2008;198:800–807.
79. T.L.Kieffer, A.D.Kwong, G.R.Picchio. Viral resistance to specifically targeted antiviral therapies for hepatitis C (STAT-Cs). J Antimicrob Chemother. 2010;65:202–212.
80. J.M.Pawlotsky, G.Germanidis, A.U.Neumann, et al. Interferon resistance of hepatitis C virus genotype 1b:relationship to nonstructural 5A gene quasispecies mutations. J Virol. 1998;72:2795–2805.
81. C.Sarrazin, T.L.Kieffer, D.Bartels, et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology. 2007;132:1767–1777.
82. S.Chevaliez, C.Rodriguez, J.-M.Pawlotsky. New virologic tools for management of chronic hepatitis B and C. Gastroenterology. 2012;142:1303–1313.
83. W.L.Irving, D.Rupp, C.P.McClure, et al. Development of a high-throughput pyrosequencing assay for monitoring temporal evolution and resistance associated variant emergence in the hepatitis C virus protease coding-region. Antiviral Res. 2014;110:52–59.
84. A.Bergfors, D.Leenheer, A.Bergqvist, et al. Analysis of hepatitis C NS5A resistance associated polymorphisms using ultra deep single molecule real time (SMRT) sequencing. Antiviral Res. 2016;126:81–89.
85. S.Fourati, J.-M.Pawlotsky. Virologic tools for HCV drug resistance testing. Viruses. 2015;7:6346–6359.•• This review describes all the tools available to investigate drug resistance in preclinical studies, clinical trials, and clinical practice.
86. A.Nasu, H.Marusawa, Y.Ueda, et al. Genetic heterogeneity of hepatitis C virus in association with antiviral therapy determined by ultra-deep sequencing. PLoS One. 2011;6:e24907.
87. M.Lauck, M.V.Alvarado-Mora, E.A.Becker, et al. Analysis of hepatitis C virus intrahost diversity across the coding region by ultradeep pyrosequencing. J Virol. 2012;86:3952–3960.
88. L.Rong, H.Dahari, R.M.Ribeiro, et al. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med. 2010;2:30ra32.
89. S.Le Pogam, A.Seshaadri, A.Kosaka, et al. Existence of hepatitis C virus NS5B variants naturally resistant to non-nucleoside, but not to nucleoside, polymerase inhibitors among untreated patients. J Antimicrob Chemother. 2008;61:1205–1216.
90. M.D.Schneider, C.Sarrazin. Antiviral therapy of hepatitis C in 2014:do we need resistance testing? Antiviral Res. 2014;105:64–71.
91. I.M.de Carvalho, R.Alves, P.A.de Souza, et al. Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV:novel insights about targeted genotyping approaches. J Med Virol. 2014;86:1714–1721.
92. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2015. J Hepatol. 2015;63:199–236.
93. D.Wyles, A.Mangia, W.Cheng, et al. Long-term persistence of HCV NS5A variants after treatment with NS5A inhibitor ledipasvir. Proceeding of the international liver congress on 50th annual meeting of the European Association for the Study of the Liver (EASL); 2015 Apr 22–26; Vienna, Austria. Abstract O059.
94. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance:AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62:932–954.
95. EASL. EASL clinical practice guidelines:management of hepatitis C virus infection. J Hepatol. 2014;60:392–420.
96. V.Soriano, A.Perelson, F.Zoulim. Why are there different dynamics in the selection of drug resistance in HIV and hepatitis B and C viruses? J Antimicrob Chemother. 2008;62(1):1–4.
97. P.Trémeaux, A.Caporossi, M.-A.Thélu, et al. Hepatitis C virus whole genome sequencing:current methods/issues and future challenges. Crit Rev Clin Lab Sci. 2016;53(5):341–351.•• This article reviews the different techniques used to sequence the HCV complete genome, before and after the introduction of NGS, and their applications.
98. J.-M.Pawlotsky. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology. 2016 Apr 11;151:70–86. doi:10.1053/j.gastro.2016.04.003.
99. J.Ito, G.Suda, Y.Yamamoto, et al. Prevalence and characteristics of naturally occurring sofosbuvir resistance-associated variants in patients with HCV genotype 1b infection. Hepatol Res. 2016 Feb 20. doi:10.1111/hepr.12685.
100. L.Benitez, P.Barreiro, P.Labarga, et al. Prevention and management of treatment failure to new oral hepatitis C drugs. Exp Opin Pharmacother. 2016;17:1215–1223.