Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance

World Journal of Gastroenterology

Volumn 22, Issue 29, 2016, Pages 6573-6581

  Jiménez Pérez, Miguel ^a   González Grande, Rocío ^a   Contreras, Pilar España ^a   Martínez, Isabel Pinazo ^a   De La Cruz Lombardo, Jesús ^a   Martín, Raúl Olmedo ^a  

^a HOSPITAL REGIONAL UNIVERSITARIO DE MÁLAGA   (Spain)

Author keywords

Direct acting antivirals; Hepatitis C virus; Resistance; Treatment

Indexed keywords

ANTIVIRUS AGENT; BOCEPREVIR; DACLATASVIR; DASABUVIR; DIRECT ACTING ANTIVIRAL AGENT; ELBASVIR; GRAZOPREVIR; HEPACIVIRIN INHIBITOR; LEDIPASVIR; NONSTRUCTURAL PROTEIN 5A INHIBITOR; OMBITASVIR; PARITAPREVIR; PEGINTERFERON; RIBAVIRIN; SIMEPREVIR; SOFOSBUVIR; TELAPREVIR; UNCLASSIFIED DRUG; NS-5 PROTEIN, HEPATITIS C VIRUS; NS3 PROTEIN, HEPATITIS C VIRUS; VIRAL PROTEIN;

ANTIVIRAL THERAPY; CHRONIC HEPATITIS C; CLINICAL PRACTICE; DRUG EFFICACY; DRUG TREATMENT FAILURE; EC50; GENETIC VARIABILITY; GENOTYPE; HOST RESISTANCE; HUMAN; IC50; NONHUMAN; RESISTANCE ASSOCIATED VARIANT; REVIEW; VIRION; VIRUS LOAD; VIRUS MORPHOLOGY; VIRUS REPLICATION; ANTAGONISTS AND INHIBITORS; ANTIVIRAL RESISTANCE; GENETICS; HEPACIVIRUS; HEPATITIS C, CHRONIC; PHYSIOLOGY; TREATMENT FAILURE;

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

EID: 84982792328     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v22.i29.6573     Document Type: Review

References (77)

1. European association for the study of the liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol 2015; 63: 199-236 [PMID: 25911336 DOI: 10.1016/j.jhep.2015.03.025]
2. 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, PMID: 26111063, DOI: 10.1002/hep.27950
3. González-Grande R, Jiménez-Pérez M, González Arjona C, Mostazo Torres J. New approaches in the treatment of hepatitis C. World J Gastroenterol 2016; 22: 1421-1432 [PMID: 26819511 DOI: 10.3748/wjg.v22.i4.1421]
4. Vermehren J, Sarrazin C. New HCV therapies on the horizon. Clin Microbiol Infect 2011; 17: 122-134 [PMID: 21087349 DOI: 10.1111/j.1469-0691.2010.03430.x]
5. Perales C, Quer J, Gregori J, Esteban JI, Domingo E. Resistance of Hepatitis C Virus to Inhibitors: Complexity and Clinical Implications. Viruses 2015; 7: 5746-5766 [PMID: 26561827 DOI: 10.3390/v7112902]
6. Perales C, Quer J, Gregori J, Esteban JI, Domingo E. Resistance of Hepatitis C Virus to Inhibitors: Complexity and Clinical Implications. Viruses 2015; 7: 5746-5766 [PMID: 26561827 DOI: 10.3390/v7112902]
7. Bacon B, Dieterich D, Flamm S, Kowdley K, Lawitz E, Milligan S, Younossi Z Naoky Tsai. Efficacy of sofosbuvir and simeprevir-based regimens for 304 HCV treatment experienced patients in a reallife setting; data from the TRIO network. [Abstract 975] 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) Nov 7-11, 2014; Boston, MA. Hepatology 2014; 60 Suppl 1: S672
8. Dieterich D, Bacon B, Flamm S, Kowdley K, Milligan S, Tsai N, Younossi Z, Lawitz E. Final evaluation of 955 HCV patients treated with 12 week regimens containing sofosbuvir/simeprevir in the TRIO network: academic and community treatment of a real-world, heterogeneous population. J Hepatol 2015; 62: S621 [DOI: 10.1016/S0168-8278(15)30978-8]
9. Reddy R, Lim JK, Kuo A, Di Bisceglie AM, Vargas HE, Galati JS, Morelli G, Everson GT, Kwo PY, Brown RS, Sulkowskim MS, Stewart TG, Akuskevich L, M. Vainorius M, Peter JA, Nelson DR, Fried MW, Manns MP. All oral HCV therapy is safe and effective in patients with decompensated cirrhosis: interim report from the HCVTARGET real world experience. J Hepatol 2015; 62: S193 [DOI: 10.1016/S0168-8278(15)30014-3]
10. Buggisch P, Sarrazin C, Mauss S, Hinrichsen H, Simon K, Vermehren J, Hueppe D, Petersen J. Sofosbuvir-based treatment under real life conditions in Germany (The SOFGER trial). J Hepatol 2015; 62: S622 [DOI: 10.1016/S0168-8278(15)30980-6]
11. Sulkowski MS, Vargas HE, Di Bisceglie AM, Kuo A, Reddy KR, Lim JK, Morelli G, Feld J , Brown RS, Frazier LM, Fried MW, Nelson DR , Jacobson I. Safety and efficacy of sofosbuvir (SOF) in combination with simeprevir (SIM) ribavirin (RBV) in patients with genotype 1: interim results of a prospective, observational study. [Abstract 955] 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) Nov 7-11, 2014; Boston, MA. Hepatology 2014; 60 Suppl 1: S660
12. Pol S, Bourliere M, Lucier S, De Ledinghen V, Zoulim F, Dorival-Mouly C, Métivier S, Larrey D, Tran A, Hezode C, Bronowicki JP, Samuel D, Marcellin P, Zarski JP, Minello A, Alric L, Trinchet JC; Nahon P on behalf of Hepather Study Group Safety and efficacy of the combination. Daclatasvir-Sofosbuvir in HCV genotype 1-monoinfected patients from the French observational cohort ANRS CO22 HEPATHER. J Hepatol 2015; 62: S258 [DOI: 10.1016/S0168-8278(15)30149-5]
13. Saxena V, Koraishy F, Sise M, Lim J, Chung R, Liapakis A, Nelson DR, Schmidt M, Fried NW, Terrault N. HCV-TARGET. Safety and efficacy of sofosbuvir-containing regimens in hepatitis C infected patients with reduced renal function: real-word experience from HCV-TARGET. J Hepatol 2015; 62: S267 [DOI: 10.1016/S0168-8278(15)30162-8]
14. Buggisch P, Petersen J, Wursthorn K, Atanasov P, Gauthier A. Real-world effectiveness of ledipasvir/sofosbuvir 8 weeks chronic hepatitis C treatment. J Hepatol 2015; 62: S280 [DOI: 10.1016/S0168-8278(15)30186-0]
15. Buti M, Riveiro-Barciela M, Esteban R. Management of directacting antiviral agent failures. J Hepatol 2015; 63: 1511-1522 [PMID: 26299621 DOI: 10.1016/j.jhep.2015.08.010]
16. Halfon P, Sarrazin C. Future treatment of chronic hepatitis C with direct acting antivirals: is resistance important? Liver Int 2012; 32 Suppl 1: 79-87 [PMID: 22212577 DOI: 10.1111/j.1478-3231.2011.02716.x]
17. Sarrazin C, Zeuzem S. Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology 2010; 138: 447-462 [PMID: 20006612 DOI: 10.1053/j.gastro.2009.11.055]
18. Sarrazin C. The importance of resistance to direct antiviral drugs in HCV infection in clinical practice. J Hepatol 2016; 64: 486-504 [PMID: 26409317 DOI: 10.1016/j.jhep.2015.09.011]
19. Wyles DL, Rodriguez-Torres M, Lawitz E, Shiffman ML, Pol S, Herring RW, Massetto B, Kanwar B, Trenkle JD, Pang PS, Zhu Y, Mo H, Brainard DM, Subramanian GM, McHutchison JG, Habersetzer F, Sulkowski MS. All-oral combination of ledipasvir, vedroprevir, tegobuvir, and ribavirin in treatment-naïve patients with genotype 1 HCV infection. Hepatology 2014; 60: 56-64 [PMID: 24501005 DOI: 10.1002/hep.27053]
20. Lontok E, Harrington P, Howe A, Kieffer T, Lennerstrand J, Lenz O, McPhee F, Mo H, Parkin N, Pilot-Matias T, Miller V. Hepatitis C virus drug resistance-associated substitutions: State of the art summary. Hepatology 2015; 62: 1623-1632 [PMID: 26095927 DOI: 10.1002/hep.27934]
21. Lindenbach BD, Rice CM. Flaviviridae: the viruses and their replication. In: Knipe DM, Howley PM, editors. Fields Virology. 5th Edition. Philadelphia: Lippincott-Raven Publishers, 2012: 1101-1152
22. Kuiken C, Simmonds P. Nomenclature and numbering of the hepatitis C virus. Methods Mol Biol 2009; 510: 33-53 [PMID: 19009252 DOI: 10.1007/978-1-59745-394-3-4]
23. Martell M, Esteban JI, Quer J, Genescà J, Weiner A, Esteban R, Guardia J, Gómez J. Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J Virol 1992; 66: 3225-3229 [PMID: 1313927]
24. Merz A, Long G, Hiet MS, Brügger B, Chlanda P, Andre P, Wieland F, Krijnse-Locker J, Bartenschlager R. Biochemical and morphological properties of hepatitis C virus particles and determination of their lipidome. J Biol Chem 2011; 286: 3018-3032 [PMID: 21056986 DOI: 10.1074/jbc.M110.175018]
25. Milam SB, Magnuson VL, Steffensen B, Chen D, Klebe RJ. IL-1 beta and prostaglandins regulate integrin mRNA expression. J Cell Physiol 1991; 149: 173-183 [PMID: 1748714 DOI: 10.1038/nrmicro16457]
26. Koutsoudakis G, Forns X, Pérez-Del-Pulgar S. [The molecular biology of hepatitis C virus]. Gastroenterol Hepatol 2013; 36: 280-293 [PMID: 23490024 DOI: 10.1016/j.gastrohep.2012.11.005]
27. Lohmann V, Körner 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 [PMID: 10390360 DOI: 10.1126/science.285.5424.110]
28. Chueca Porcuna N, Alvarez Estévez M, Parra Ruiz J, Hernández Quero J, García García F. [Update on hepatitis C therapy. New drugs, treatment response monitoring and emergence of resistance]. Enferm Infecc Microbiol Clin 2013; 31 Suppl 1: 40-47 [PMID: 23453230 DOI: 10.1016/S0213-005X(13)70113-7]
29. Pawlotsky JM. Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology 2011; 53: 1742-1751 [PMID: 21374691 DOI: 10.1002/hep.24262]
30. Pawlotsky JM. Hepatitis C virus genetic variability: pathogenic and clinical implications. Clin Liver Dis 2003; 7: 45-66 [PMID: 12691458 DOI: 10.1016/S1089-3261(02)00065-]
31. Rong L, Dahari H, Ribeiro RM, Perelson AS. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2010; 2: 30ra32 [PMID: 20445200 DOI: 10.1126/scitranslmed.3000544]
32. Herrmann E, Neumann AU, Schmidt JM, Zeuzem S. Hepatitis C virus kinetics. Antivir Ther 2000; 5: 85-90 [PMID: 10971860]
33. Powdrill MH, Tchesnokov EP, Kozak RA, Russell RS, Martin R, Svarovskaia ES, Mo H, Kouyos RD, Götte M. Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance. Proc Natl Acad Sci USA 2011; 108: 20509-20513 [PMID: 22135458 DOI: 10.1073/pnas.1105797108]
34. Lataillade M, Chiarella J, Yang R, Schnittman S, Wirtz V, Uy J, Seekins D, Krystal M, Mancini M, McGrath D, Simen B, Egholm M, Kozal M. Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naïve subjects in the CASTLE study. PLoS One 2010; 5: e10952 [PMID: 20532178 DOI: 10.1371/journal.pone.0010952]
35. Verbinnen T, Van Marck H, Vandenbroucke I, Vijgen L, Claes M, Lin TI, Simmen K, Neyts J, Fanning G, Lenz O. Tracking the evolution of multiple in vitro hepatitis C virus replicon variants under protease inhibitor selection pressure by 454 deep sequencing. J Virol 2010; 84: 11124-11133 [PMID: 20739521 DOI: 10.1128/JVI.01217-10]
36. Soriano V, Perelson AS, Zoulim F. Why are there different dynamics in the selection of drug resistance in HIV and hepatitis B and C viruses? J Antimicrob Chemother 2008; 62: 1-4 [PMID: 18441341 DOI: 10.1093/jac/dkn175]
37. McCown MF, Rajyaguru S, Kular S, Cammack N, Nájera I. GT-1a or GT-1b subtype-specific resistance profiles for hepatitis C virus inhibitors telaprevir and HCV-796. Antimicrob Agents Chemother 2009; 53: 2129-2132 [PMID: 19273674 DOI: 10.1128/AAC.01598-08]
38. Martin B, Hennecke N, Lohmann V, Kayser A, Neumann-Haefelin C, Kukolj G, Böcher WO, Thimme R. Restoration of HCV-specific CD8+ T cell function by interferon-free therapy. J Hepatol 2014; 61: 538-543 [PMID: 24905492 DOI: 10.1016/j.jhep.2014.05.043]
39. Larrubia JR, Moreno-Cubero E, Miquel J, Sanz-de-Villalobos E. Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control. World J Gastroenterol 2015; 21: 3480-3491 [PMID: 25834312 DOI: 10.3748/wjg.v21. i12.3480]
40. Dietz J, Schelhorn SE, Fitting D, Mihm U, Susser S, Welker MW, Füller C, Däumer M, Teuber G, Wedemeyer H, Berg T, Lengauer T, Zeuzem S, Herrmann E, Sarrazin C. Deep sequencing reveals mutagenic effects of ribavirin during monotherapy of hepatitis C virus genotype 1-infected patients. J Virol 2013; 87: 6172-6181 [PMID: 23536652 DOI: 10.1128/JVI.02778-12]
41. Howe AY, Black S, Curry S, Ludmerer SW, Liu R, Barnard RJ, Newhard W, Hwang PM, Nickle D, Gilbert C, Caro L, DiNubile MJ, Mobashery N. Virologic resistance analysis from a phase 2 study of MK-5172 combined with pegylated interferon/ribavirin in treatmentnaive patients with hepatitis C virus genotype 1 infection. Clin Infect Dis 2014; 59: 1657-1665 [PMID: 25266289 DOI: 10.1093/cid/ciu696]
42. Thompson AJ, Locarnini SA, Beard MR. Resistance to anti-HCV protease inhibitors. Curr Opin Virol 2011; 1: 599-606 [PMID: 22440917 DOI: 10.1016/j.coviro.2011.10.001]
43. Wyles DL. Antiviral resistance and the future landscape of hepatitis C virus infection therapy. J Infect Dis 2013; 207 Suppl 1: S33-S39 [PMID: 23390303 DOI: 10.1093/infdis/jis761]
44. Sarrazin C, Lathouwers E, Peeters M, Daems B, Buelens A, Witek J, Wyckmans Y, Fevery B, Verbinnen T, Ghys A, Schlag M, Baldini A, De Meyer S, Lenz O. Prevalence of the hepatitis C virus NS3 polymorphism Q80K in genotype 1 patients in the European region. Antiviral Res 2015; 116: 10-16 [PMID: 25614456 DOI: 10.1016/j.antiviral.2015.01.003]
45. Sullivan JC, De Meyer S, Bartels DJ, Dierynck I, Zhang EZ, Spanks J, Tigges AM, Ghys A, Dorrian J, Adda N, Martin EC, Beumont M, Jacobson IM, Sherman KE, Zeuzem S, Picchio G, Kieffer TL. Evolution of treatment-emergent resistant variants in telaprevir phase 3 clinical trials. Clin Infect Dis 2013; 57: 221-229 [PMID: 23575197 DOI: 10.1093/cid/cit226]
46. Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, Buelens A, Ceulemans H, Beumont M, Picchio G, De Meyer S. 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 [PMID: 25445400 DOI: 10.1016/j.jhep.2014.11.032]
47. Yeh WW, Lipardi C, Jumes P, De Lepeleire IM, Van den Bulk N, Caro L, Huang X, Mangin E, Nachbar RB, Gane EJ, Popa S, Ghicavii N, Wagner FD, Butterton JR. MK-8742, a HCV NS5A inhibitor with a broad spectrum of HCV genotypic activity, demonstrates potent antiviral activity in genotype-1 and-3 HCV infected patients. [Abstract 479] 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) Nov 1-5, 2013; Washington DC. Hepatology 2013; 58 Suppl 1: 438a-439a
48. Lahser F, Liu R, Bystol K, Xia E, Raubertas R, Asante-Appiah E. A combination containing MK-5172 (HCV NS3 protease inhibitor) and MK-8742 (HCV NS5A inhibitor) demonstrates high barrier to resistance in HCV replicons. [Abstract 87] 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) Nov 9-13, 2012; Boston, MA. Hepatology 2012; 56: 236a
49. Gao M. Antiviral activity and resistance of HCV NS5A replication complex inhibitors. Curr Opin Virol 2013; 3: 514-520 [PMID: 23896281 DOI: 10.1016/j.coviro.2013.06.014]
50. Nakamoto S, Kanda T, Wu S, Shirasawa H, Yokosuka O. Hepatitis C virus NS5A inhibitors and drug resistance mutations. World J Gastroenterol 2014; 20: 2902-2912 [PMID: 24659881 DOI: 10.3748/wjg.v20.i11.2902]
51. Krishnan P, Tripathi R, Schnell G, Reisch T, Beyer J, Dekhtyar T, Irvin M, Xie W, Larsen L, Podsadecki T, Pilot-Matias T, Collins C. Long term follow-up of treatment-emergent resistance-associated variants in NS3, NS5A and NS5B with paritaprevir/r, ombitasvirand dasabuvir-based regimens. J Hepatol 2015; 62: S220-S220 [DOI: 10.1016/S0168-8278(15)30071-4]
52. Susser S, Vermehren J, Forestier N, Welker MW, Grigorian N, Füller C, Perner D, Zeuzem S, Sarrazin C. Analysis of longterm persistence of resistance mutations within the hepatitis C virus NS3 protease after treatment with telaprevir or boceprevir. J Clin Virol 2011; 52: 321-327 [PMID: 21924672 DOI: 10.1016/j.jcv.2011.08.015]
53. Thomas XV, de Bruijne J, Kieffer TL, Sullivan JC, Rebers SP, deVries M, Reesink HW, Weegink CJ, Molenkamp R, Schinkel J. Long-term follow-up of chronic hepatitis C infected patients treated with telaprevir: evaluation of persistence of resistant variants by ultra-deep sequencing. J Hepatol 2011; 54: S490-S491 [DOI: 10.1016/S0168-8278(11)61244-0]
54. McPhee F, Hernandez D, Yu F, Ueland J, Monikowski A, Carifa A, Falk P, Wang C, Fridell R, Eley T, Zhou N, Gardiner D. Resistance analysis of hepatitis C virus genotype 1 prior treatment null responders receiving daclatasvir and asunaprevir. Hepatology 2013; 58: 902-911 [PMID: 23504694 DOI: 10.1002/hep.26388]
55. Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, Hindes RG, Berrey MM. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med 2013; 368: 34-44 [PMID: 23281974 DOI: 10.1056/NEJMoa1208953]
56. Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Bräu N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014; 370: 1889-1898 [PMID: 24725239 DOI: 10.1056/NEJMoa1402454]
57. Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014; 370: 1483-1493 [PMID: 24725238 DOI: 10.1056/NEJMoa1316366]
58. Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, Shiffman ML, Schiff E, Ghalib R, Ryan M, Rustgi V, Chojkier M, Herring R, Di Bisceglie AM, Pockros PJ, Subramanian GM, An D, Svarovskaia E, Hyland RH, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Pound D, Fried MW. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 2014; 370: 1879-1888 [PMID: 24720702 DOI: 10.1056/NEJMoa1402355]
59. Lawitz EJ, Rodriguez-Torres M, Denning J, Mathias A, Mo H, Gao B, Cornpropst MT, Berrey MM, Symonds WT. All-oral therapy with nucleotide inhibitors sofosbuvir and GS-0938 for 14 days in treatment-naive genotype 1 hepatitis C (nuclear). J Viral Hepat 2013; 20: 699-707 [PMID: 24010644 DOI: 10.1111/jvh.12091]
60. Lam AM, Espiritu C, Bansal S, Micolochick Steuer HM, Niu C, Zennou V, Keilman M, Zhu Y, Lan S, Otto MJ, Furman PA. Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus. Antimicrob Agents Chemother 2012; 56: 3359-3368 [PMID: 22430955 DOI: 10.1128/AAC.00054-12]
61. Tong X, Le Pogam S, Li L, Haines K, Piso K, Baronas V, Yan JM, So SS, Klumpp K, Nájera I. In vivo emergence of a novel mutant L159F/L320F in the NS5B polymerase confers low-level resistance to the HCV polymerase inhibitors mericitabine and sofosbuvir. J Infect Dis 2014; 209: 668-675 [PMID: 24154738 DOI: 10.1093/infdis/jit562]
62. Childs-Kean LM, Hand EO. Simeprevir and sofosbuvir for treatment of chronic hepatitis C infection. Clin Ther 2015; 37: 243-267 [PMID: 25601269 DOI: 10.1016/j.clinthera.2014.12.012]
63. Hedskog C, Dvory-Sobol H, Gontcharova V, Martin R, Ouyang W, Han B, Gane EJ, Brainard D, Hyland RH, Miller MD, Mo H, Svarovskaia E. Evolution of the HCV viral population from a patient with S282T detected at relapse after sofosbuvir monotherapy. J Viral Hepat 2015; 22: 871-881 [PMID: 25784085 DOI: 10.1111/jvh.12405]
64. Svarovskaia ES, Dvory-Sobol H, Parkin N, Hebner C, Gontcharova V, Martin R, Ouyang W, Han B, Xu S, Ku K, Chiu S, Gane E, Jacobson IM, Nelson DR, Lawitz E, Wyles DL, Bekele N, Brainard D, Symonds WT, McHutchison JG, Miller MD, Mo H. 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 [PMID: 25266287 DOI: 10.1093/cid/ciu697]
65. Krishnan P, Tripathi R, Schnell G, Reisch T, Beyer J, Irvin M, Xie W, Larsen L, Podsadecki T, Pilot-Matias T, Collinet C. 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. [Abstract 1936] 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) Nov 7-11, 2014; Boston, MA. Hepatology 2014; 60 Suppl 1: 1134a-1135a
66. Kati W, Koev G, Irvin M, Beyer J, Liu Y, Krishnan P, Reisch T, Mondal R, Wagner R, Molla A, Maring C, Collins C. In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother 2015; 59: 1505-1511 [PMID: 25534735 DOI: 10.1128/AAC.04619-14]
67. Vermehren J, Sarrazin C. The role of resistance in HCV treatment. Best Pract Res Clin Gastroenterol 2012; 26: 487-503 [PMID: 23199507 DOI: 10.1016/j.bpg.2012.09.011]
68. Margeridon-Thermet S, Le Pogam S, Li L, Liu TF, Shulman N, Shafer RW, Najera I. Similar prevalence of low-abundance drugresistant variants in treatment-naive patients with genotype 1a and 1b hepatitis C virus infections as determined by ultradeep pyrosequencing. PLoS One 2014; 9: e105569 [PMID: 25140696 DOI: 10.1371/journal.pone.0105569]
69. Paolucci S, Fiorina L, Mariani B, Gulminetti R, Novati S, Barbarini G, Bruno R, Baldanti F. Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-naïve patients. Virol J 2013; 10: 355 [PMID: 24341898 DOI: 10.1186/1743-422X-10-355]
70. Suzuki F, Sezaki H, Akuta N, Suzuki Y, Seko Y, Kawamura Y, Hosaka T, Kobayashi M, Saito S, Arase Y, Ikeda K, Kobayashi M, Mineta R, Watahiki S, Miyakawa Y, Kumada H. Prevalence of hepatitis C virus variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients with genotype 1b. J Clin Virol 2012; 54: 352-354 [PMID: 22658798 DOI: 10.1016/j.jcv.2012.04.024]
71. McCloskey RM, Liang RH, Joy JB, Krajden M, Montaner JS, Harrigan PR, Poon AF. Global origin and transmission of hepatitis C virus nonstructural protein 3 Q80K polymorphism. J Infect Dis 2015; 211: 1288-1295 [PMID: 25389307 DOI: 10.1093/infdis/jiu613]
72. Ruggiero T, Proietti A, Boglione L, Milia MG, Allice T, Burdino E, Orofino G, Bonora S, Di Perri G, Ghisetti V. Predominance of hepatitis C virus Q80K among NS3 baseline-resistance-associated amino acid variants in direct-antiviral-agent-naïve patients with chronic hepatitis: single-centre experience. Arch Virol 2015; 160: 2881-2885 [PMID: 26249823 DOI: 10.1007/s00705-015-2563-3]
73. Jacobson IM, Dore GJ, Foster GR, Fried MW, Radu M, Rafalsky VV, Moroz L, Craxi A, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, De La Rosa G, Kalmeijer R, Scott J, Sinha R, Beumont-Mauviel M. 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, placebocontrolled trial. Lancet 2014; 384: 403-413 [PMID: 24907225 DOI: 10.1016/S0140-6736(14)60494-3]
74. Manns M, Marcellin P, Poordad F, de Araujo ES, Buti M, Horsmans Y, Janczewska E, Villamil F, Scott J, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, De La Rosa G, Kalmeijer R, Sinha R, Beumont-Mauviel M. 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 [PMID: 24907224 DOI: 10.1016/S0140-6736(14)60538-9]
75. Chatterji U, Lim P, Bobardt MD, Wieland S, Cordek DG, Vuagniaux G, Chisari F, Cameron CE, Targett-Adams P, Parkinson T, Gallay PA. HCV resistance to cyclosporin A does not correlate with a resistance of the NS5A-cyclophilin A interaction to cyclophilin inhibitors. J Hepatol 2010; 53: 50-56 [PMID: 20451281 DOI: 10.1016/j.jhep.2010.01.041]
76. Yoshimi S, Imamura M, Murakami E, Hiraga N, Tsuge M, Kawakami Y, Aikata H, Abe H, Hayes CN, Sasaki T, Ochi H, Chayama K. 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 [PMID: 25954851 DOI: 10.1002/jmv.24255]
77. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, Everson GT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D, Hindes R, Symonds W, Pasquinelli C, Grasela DM. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014; 370: 211-221 [PMID: 24428467 DOI: 10.1056/NEJMoa1306218]