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Antiviral Consideration for Transplantation Including Drug Resistance

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Book cover Principles and Practice of Transplant Infectious Diseases

Abstract

Antiviral therapy is required in the transplant setting for viral infections that arise from preexisting latent or persistent infection in the recipient and/or donor as well as from nosocomial or community sources. A preventive or prophylactic antiviral approach where feasible is preferable to the treatment of symptomatic viral disease. Acute infections need prompt diagnosis and antiviral treatment for the best outcome. Selection of antiviral therapy involves multiple considerations including potential benefit, toxicity, logistical complexity, and the possibility of drug resistance. This chapter reviews antiviral drug therapy for the most common viruses affecting transplant recipients: herpesviruses including herpes simplex virus, varicella-zoster virus, and cytomegalovirus, influenza, respiratory syncytial virus (RSV), and hepatitis viruses B and C. The mechanism of action, major pharmacologic features, therapeutic uses related to transplant recipients, and genetic pathways of antiviral drug resistance are described for the FDA-approved drugs and some experimental compounds in late stage clinical trial.

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References

  1. Meng Q, Hagemeier SR, Fingeroth JD, Gershburg E, Pagano JS, Kenney SC. The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production. J Virol. 2010;84(9):4534–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Talarico CL, Burnette TC, Miller WH, Smith SL, Davis MG, Stanat SC, et al. Acyclovir is phosphorylated by the human cytomegalovirus UL97 protein. Antimicrob Agents Chemother. 1999;43(8):1941–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Earnshaw DL, Bacon TH, Darlison SJ, Edmonds K, Perkins RM, Vere Hodge RA. Mode of antiviral action of penciclovir in MRC-5 cells infected with herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus. Antimicrob Agents Chemother. 1992;36(12):2747–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Laskin OL, de Miranda P, King DH, Page DA, Longstreth JA, Rocco L, et al. Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans. Antimicrob Agents Chemother. 1982;21(5):804–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Smith JP, Weller S, Johnson B, Nicotera J, Luther JM, Haas DW. Pharmacokinetics of acyclovir and its metabolites in cerebrospinal fluid and systemic circulation after administration of high-dose valacyclovir in subjects with normal and impaired renal function. Antimicrob Agents Chemother. 2010;54(3):1146–51.

    Article  CAS  PubMed  Google Scholar 

  6. Tyring SK, Baker D, Snowden W. Valacyclovir for herpes simplex virus infection: long-term safety and sustained efficacy after 20 years’ experience with acyclovir. J Infect Dis. 2002;186(Suppl 1):S40–6.

    Article  CAS  PubMed  Google Scholar 

  7. Bell WR, Chulay JD, Feinberg JE. Manifestations resembling thrombotic microangiopathy in patients with advanced human immunodeficiency virus (HIV) disease in a cytomegalovirus prophylaxis trial (ACTG 204). Medicine (Baltimore). 1997;76(5):369–80.

    Article  CAS  Google Scholar 

  8. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143–238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ullmann AJ, Schmidt-Hieber M, Bertz H, Heinz WJ, Kiehl M, Kruger W, et al. Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ann Hematol. 2016;95(9):1435–55.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Pergam SA, Limaye AP. Varicella zoster virus in solid organ transplantation. Am J Transplant. 2013;13(Suppl 4):138–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wilck MB, Zuckerman RA. Herpes simplex virus in solid organ transplantation. Am J Transplant. 2013;13(Suppl 4):121–7.

    Article  CAS  PubMed  Google Scholar 

  12. Slifkin M, Doron S, Snydman DR. Viral prophylaxis in organ transplant patients. Drugs. 2004;64(24):2763–92.

    Article  CAS  PubMed  Google Scholar 

  13. Piret J, Boivin G. Antiviral drug resistance in herpesviruses other than cytomegalovirus. Rev Med Virol. 2014;24(3):186–218.

    Article  CAS  PubMed  Google Scholar 

  14. Sauerbrei A, Deinhardt S, Zell R, Wutzler P. Phenotypic and genotypic characterization of acyclovir-resistant clinical isolates of herpes simplex virus. Antivir Res. 2010;86(3):246–52.

    Article  CAS  PubMed  Google Scholar 

  15. Andrei G, Topalis D, Fiten P, McGuigan C, Balzarini J, Opdenakker G, et al. In vitro-selected drug-resistant varicella-zoster virus mutants in the thymidine kinase and DNA polymerase genes yield novel phenotype-genotype associations and highlight differences between antiherpesvirus drugs. J Virol. 2012;86(5):2641–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sarisky RT, Quail MR, Clark PE, Nguyen TT, Halsey WS, Wittrock RJ, et al. Characterization of herpes simplex viruses selected in culture for resistance to penciclovir or acyclovir. J Virol. 2001;75(4):1761–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bacon TH, Levin MJ, Leary JJ, Sarisky RT, Sutton D. Herpes simplex virus resistance to acyclovir and penciclovir after two decades of antiviral therapy. Clin Microbiol Rev. 2003;16(1):114–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Topalis D, Gillemot S, Snoeck R, Andrei G. Distribution and effects of amino acid changes in drug-resistant alpha and beta herpesviruses DNA polymerase. Nucleic Acids Res. 2016;44(20):9530–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Crumpacker CS. Ganciclovir. N Engl J Med. 1996;335(10):721–9.

    Article  CAS  PubMed  Google Scholar 

  20. Field AK, Davies ME, DeWitt C, Perry HC, Liou R, Germershausen J, et al. 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine: a selective inhibitor of herpes group virus replication. Proc Natl Acad Sci U S A. 1983;80(13):4139–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gentry BG, Drach JC. Metabolism of cyclopropavir and ganciclovir in human cytomegalovirus-infected cells. Antimicrob Agents Chemother. 2014;58(4):2329–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Lischka P, Hewlett G, Wunberg T, Baumeister J, Paulsen D, Goldner T, et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother. 2010;54(3):1290–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pescovitz MD, Pruett TL, Gonwa T, Brook B, McGory R, Wicker K, et al. Oral ganciclovir dosing in transplant recipients and dialysis patients based on renal function. Transplantation. 1998;66(8):1104–7.

    Article  CAS  PubMed  Google Scholar 

  24. Danziger-Isakov L, Mark BG. Hematologic complications of anti-CMV therapy in solid organ transplant recipients. Clin Transpl. 2009;23(3):295–304.

    Article  Google Scholar 

  25. Salzberger B, Bowden RA, Hackman RC, Davis C, Boeckh M. Neutropenia in allogeneic marrow transplant recipients receiving ganciclovir for prevention of cytomegalovirus disease: risk factors and outcome. Blood. 1997;90(6):2502–8.

    CAS  PubMed  Google Scholar 

  26. Shepp DH, Dandliker PS, de Miranda P, Burnette TC, Cederberg DM, Kirk LE, et al. Activity of 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine in the treatment of cytomegalovirus pneumonia. Ann Intern Med. 1985;103(3):368–73.

    Article  CAS  PubMed  Google Scholar 

  27. McGavin JK, Goa KL. Ganciclovir: an update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients. Drugs. 2001;61(8):1153–83.

    Article  CAS  PubMed  Google Scholar 

  28. Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B, et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004;4(4):611–20.

    Article  CAS  PubMed  Google Scholar 

  29. Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Danziger-Isakov L, et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2013;96(4):333–60.

    Article  CAS  PubMed  Google Scholar 

  30. Humar A, Lebranchu Y, Vincenti F, Blumberg EA, Punch JD, Limaye AP, et al. The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am J Transplant. 2010;10(5):1228–37.

    Article  CAS  PubMed  Google Scholar 

  31. Asberg A, Humar A, Rollag H, Jardine AG, Mouas H, Pescovitz MD, et al. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2007;7(9):2106–13.

    Article  CAS  PubMed  Google Scholar 

  32. Lurain NS, Chou S. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev. 2010;23(4):689–712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chou S, Ercolani RJ, Vanarsdall AL. Differentiated levels of ganciclovir resistance conferred by mutations at Codons 591 to 603 of the Cytomegalovirus UL97 Kinase Gene. J Clin Microbiol. 2017;55(7):2098–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Komatsu TE, Pikis A, Naeger LK, Harrington PR. Resistance of human cytomegalovirus to ganciclovir/valganciclovir: a comprehensive review of putative resistance pathways. Antivir Res. 2014;101:12–25.

    Article  CAS  PubMed  Google Scholar 

  35. Wagstaff AJ, Bryson HM. Foscarnet. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. Drugs. 1994;48(2):199–226.

    Article  CAS  PubMed  Google Scholar 

  36. Bacigalupo A, Boyd A, Slipper J, Curtis J, Clissold S. Foscarnet in the management of cytomegalovirus infections in hematopoietic stem cell transplant patients. Expert Rev Anti-Infect Ther. 2012;10(11):1249–64.

    Article  CAS  PubMed  Google Scholar 

  37. Avery RK, Arav-Boger R, Marr KA, Kraus E, Shoham S, Lees L, et al. Outcomes in transplant recipients treated with foscarnet for ganciclovir-resistant or refractory cytomegalovirus infection. Transplantation. 2016;100(10):e74–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Reusser P, Einsele H, Lee J, Volin L, Rovira M, Engelhard D, et al. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood. 2002;99(4):1159–64.

    Article  CAS  PubMed  Google Scholar 

  39. De Clercq E. Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. Clin Microbiol Rev. 2003;16(4):569–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Ljungman P, Deliliers GL, Platzbecker U, Matthes-Martin S, Bacigalupo A, Einsele H, et al. Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2001;97(2):388–92.

    Article  CAS  PubMed  Google Scholar 

  41. Scott RA, Pavesio C. Ocular side-effects from systemic HPMPC (Cidofovir) for a non-ocular cytomegalovirus infection. Am J Ophthalmol. 2000;130(1):126–7.

    Article  CAS  PubMed  Google Scholar 

  42. Painter W, Robertson A, Trost LC, Godkin S, Lampert B, Painter G. First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Antimicrob Agents Chemother. 2012;56(5):2726–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227–36.

    Article  CAS  PubMed  Google Scholar 

  44. Ljungman P, Ribaud P, Eyrich M, Matthes-Martin S, Einsele H, Bleakley M, et al. Cidofovir for adenovirus infections after allogeneic hematopoietic stem cell transplantation: a survey by the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2003;31(6):481–6.

    Article  CAS  PubMed  Google Scholar 

  45. Florescu DF, Pergam SA, Neely MN, Qiu F, Johnston C, Way S, et al. Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients. Biol Blood Marrow Transplant. 2012;18(5):731–8.

    Article  CAS  PubMed  Google Scholar 

  46. Duan R, de Vries RD, Osterhaus AD, Remeijer L, Verjans GM. Acyclovir-resistant corneal HSV-1 isolates from patients with herpetic keratitis. J Infect Dis. 2008;198(5):659–63.

    Article  CAS  PubMed  Google Scholar 

  47. Frobert E, Burrel S, Ducastelle-Lepretre S, Billaud G, Ader F, Casalegno JS, et al. Resistance of herpes simplex viruses to acyclovir: an update from a ten-year survey in France. Antivir Res. 2014;111:36–41.

    Article  CAS  PubMed  Google Scholar 

  48. van der Beek MT, Vermont CL, Bredius RG, Marijt EW, van der Blij-de Brouwer CS, Kroes AC, et al. Persistence and antiviral resistance of varicella zoster virus in hematological patients. Clin Infect Dis. 2013;56(3):335–43.

    Google Scholar 

  49. Fisher CE, Knudsen JL, Lease ED, Jerome KR, Rakita RM, Boeckh M, et al. Risk factors and outcomes of ganciclovir resistant cytomegalovirus infection in solid organ transplant recipients. Clin Infect Dis. 2017;65(1):57–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sahoo MK, Lefterova MI, Yamamoto F, Waggoner JJ, Chou S, Holmes SP, et al. Detection of cytomegalovirus drug resistance mutations by next-generation sequencing. J Clin Microbiol. 2013;51(11):3700–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Chou S, Boivin G, Ives J, Elston R. Phenotypic evaluation of previously uncharacterized cytomegalovirus DNA polymerase sequence variants detected in a valganciclovir treatment trial. J Infect Dis. 2014;209(8):1219–26.

    Article  CAS  PubMed  Google Scholar 

  52. Chou S, Ercolani RJ, Sahoo MK, Lefterova MI, Strasfeld LM, Pinsky BA. Improved detection of emerging drug-resistant mutant cytomegalovirus subpopulations by deep sequencing. Antimicrob Agents Chemother. 2014;58(8):4697–702.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. James SH, Larson KB, Acosta EP, Prichard MN. Helicase-primase as a target of new therapies for herpes simplex virus infections. Clin Pharmacol Ther. 2015;97(1):66–78.

    Article  CAS  PubMed  Google Scholar 

  54. Weller SK, Kuchta RD. The DNA helicase-primase complex as a target for herpes viral infection. Expert Opin Ther Targets. 2013;17(10):1119–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Tyring S, Wald A, Zadeikis N, Dhadda S, Takenouchi K, Rorig R. ASP2151 for the treatment of genital herpes: a randomized, double-blind, placebo- and valacyclovir-controlled, dose-finding study. J Infect Dis. 2012;205(7):1100–10.

    Article  CAS  PubMed  Google Scholar 

  56. Wald A, Corey L, Timmler B, Magaret A, Warren T, Tyring S, et al. Helicase-primase inhibitor pritelivir for HSV-2 infection. N Engl J Med. 2014;370(3):201–10.

    Article  CAS  PubMed  Google Scholar 

  57. Wald A, Timmler B, Magaret A, Warren T, Tyring S, Johnston C, et al. Effect of pritelivir compared with valacyclovir on genital HSV-2 shedding in patients with frequent recurrences: A randomized clinical trial. JAMA. 2016;316(23):2495–503.

    Article  CAS  PubMed  Google Scholar 

  58. Chono K, Katsumata K, Kontani T, Shiraki K, Suzuki H. Characterization of virus strains resistant to the herpes virus helicase-primase inhibitor ASP2151 (Amenamevir). Biochem Pharmacol. 2012;84(4):459–67.

    Article  CAS  PubMed  Google Scholar 

  59. Field HJ, Biswas S. Antiviral drug resistance and helicase-primase inhibitors of herpes simplex virus. Drug Resist Updat. 2011;14(1):45–51.

    Article  CAS  PubMed  Google Scholar 

  60. Edlefsen PT, Birkmann A, Huang ML, Magaret CA, Kee JJ, Diem K, et al. No evidence of pritelivir resistance among herpes simplex virus type 2 isolates after 4 weeks of daily therapy. J Infect Dis. 2016;214(2):258–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Biron KK, Harvey RJ, Chamberlain SC, Good SS, Smith AA 3rd, Davis MG, et al. Potent and selective inhibition of human cytomegalovirus replication by 1263 W94, a benzimidazole L-riboside with a unique mode of action. Antimicrob Agents Chemother. 2002;46(8):2365–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chou S, Van Wechel LC, Marousek GI. Effect of cell culture conditions on the anticytomegalovirus activity of maribavir. Antimicrob Agents Chemother. 2006;50(7):2557–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Marty FM, Ljungman P, Papanicolaou GA, Winston DJ, Chemaly RF, Strasfeld L, et al. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis. 2011;11(4):284–92.

    Article  CAS  PubMed  Google Scholar 

  64. Winston DJ, Saliba F, Blumberg E, Abouljoud M, Garcia-Diaz JB, Goss JA, et al. Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial. Am J Transplant. 2012;12(11):3021–30.

    Article  CAS  PubMed  Google Scholar 

  65. Avery RK, Marty FM, Strasfeld L, Lee I, Arrieta A, Chou S, et al. Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients. Transpl Infect Dis. 2010;12(6):489–96.

    Article  CAS  PubMed  Google Scholar 

  66. Strasfeld L, Lee I, Tatarowicz W, Villano S, Chou S. Virologic characterization of multidrug-resistant cytomegalovirus infection in 2 transplant recipients treated with maribavir. J Infect Dis. 2010;202(1):104–8.

    Article  CAS  PubMed  Google Scholar 

  67. Chou S. Cytomegalovirus UL97 mutations in the era of ganciclovir and maribavir. Rev Med Virol. 2008;18(4):233–46.

    Article  CAS  PubMed  Google Scholar 

  68. Chou S, Ercolani RJ, Marousek G, Bowlin TL. Cytomegalovirus UL97 kinase catalytic domain mutations that confer multidrug resistance. Antimicrob Agents Chemother. 2013;57(7):3375–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bigley TM, Reitsma JM, Terhune SS. Antagonistic relationship between human cytomegalovirus pUL27 and pUL97 activities during infection. J Virol. 2015;89(20):10230–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chou S. Diverse cytomegalovirus UL27 mutations adapt to loss of viral UL97 kinase activity under maribavir. Antimicrob Agents Chemother. 2009;53(1):81–5.

    Article  CAS  PubMed  Google Scholar 

  71. Goldner T, Hewlett G, Ettischer N, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol. 2011;85(20):10884–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Neuber S, Wagner K, Goldner T, Lischka P, Steinbrueck L, Messerle M, et al. Mutual Interplay between the Human Cytomegalovirus Terminase Subunits pUL51, pUL56, and pUL89 Promotes Terminase Complex Formation. J Virol. 2017;91(12):e02384-16.

    Google Scholar 

  73. Chemaly RF, Ullmann AJ, Stoelben S, Richard MP, Bornhauser M, Groth C, et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;370(19):1781–9.

    Article  CAS  PubMed  Google Scholar 

  74. Chou S. Rapid in vitro evolution of human cytomegalovirus UL56 mutations that confer letermovir resistance. Antimicrob Agents Chemother. 2015;59(10):6588–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Goldner T, Hempel C, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. Geno- and phenotypic characterization of human cytomegalovirus mutants selected in vitro after letermovir (AIC246) exposure. Antimicrob Agents Chemother. 2014;58(1):610–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Lischka P, Michel D, Zimmermann H. Characterization of cytomegalovirus breakthrough events in a Phase 2 prophylaxis trial of letermovir (AIC246, MK 8228). J Infect Dis. 2016;213(1):23–30.

    Article  CAS  PubMed  Google Scholar 

  77. Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med. 2005;353(13):1363–73.

    Article  CAS  PubMed  Google Scholar 

  78. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015;385(9979):1729–37.

    Article  CAS  PubMed  Google Scholar 

  79. Toovey S, Prinssen EP, Rayner CR, Thakrar BT, Dutkowski R, Koerner A, et al. Post-marketing assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: an updated review. Adv Ther. 2012;29(10):826–48.

    Article  PubMed  Google Scholar 

  80. McLaughlin MM, Skoglund EW, Ison MG. Peramivir: an intravenous neuraminidase inhibitor. Expert Opin Pharmacother. 2015;16(12):1889–900.

    Article  CAS  PubMed  Google Scholar 

  81. Hsu J, Santesso N, Mustafa R, Brozek J, Chen YL, Hopkins JP, et al. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann Intern Med. 2012;156(7):512–24.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Harper SA, Bradley JS, Englund JA, File TM, Gravenstein S, Hayden FG, et al. Seasonal influenza in adults and children--diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(8):1003–32.

    Article  CAS  PubMed  Google Scholar 

  83. Kumar D, Morris MI, Kotton CN, Fischer SA, Michaels MG, Allen U, et al. Guidance on novel influenza A/H1N1 in solid organ transplant recipients. Am J Transplant. 2010;10(1):18–25.

    Article  CAS  PubMed  Google Scholar 

  84. Ison MG, Hui DS, Clezy K, O’Neil BJ, Flynt A, Collis PJ, et al. A clinical trial of intravenous peramivir compared with oral oseltamivir for the treatment of seasonal influenza in hospitalized adults. Antivir Ther. 2013;18(5):651–61.

    Article  CAS  PubMed  Google Scholar 

  85. Welliver R, Monto AS, Carewicz O, Schatteman E, Hassman M, Hedrick J, et al. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA. 2001;285(6):748–54.

    Article  CAS  PubMed  Google Scholar 

  86. Hayden FG, Gubareva LV, Monto AS, Klein TC, Elliot MJ, Hammond JM, et al. Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group. N Engl J Med. 2000;343(18):1282–9.

    Article  CAS  PubMed  Google Scholar 

  87. Pizzorno A, Abed Y, Boivin G. Influenza drug resistance. Semin Respir Crit Care Med. 2011;32(4):409–22.

    Article  PubMed  Google Scholar 

  88. van der Vries E, Schutten M, Boucher CA. The potential for multidrug-resistant influenza. Curr Opin Infect Dis. 2011;24(6):599–604.

    Article  PubMed  CAS  Google Scholar 

  89. Li L, Avery R, Budev M, Mossad S, Danziger-Isakov L. Oral versus inhaled ribavirin therapy for respiratory syncytial virus infection after lung transplantation. J Heart Lung Transplant. 2012;31(8):839–44.

    Article  PubMed  Google Scholar 

  90. Shah JN, Chemaly RF. Management of RSV infections in adult recipients of hematopoietic stem cell transplantation. Blood. 2011;117(10):2755–63.

    Article  CAS  PubMed  Google Scholar 

  91. Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16(1):37–48.

    Article  CAS  PubMed  Google Scholar 

  92. Riner A, Chan-Tack KM, Murray JS. Original research: Intravenous ribavirin--review of the FDA’s Emergency Investigational New Drug Database (1997–2008) and literature review. Postgrad Med. 2009;121(3):139–46.

    Article  PubMed  Google Scholar 

  93. Preston SL, Drusano GL, Glue P, Nash J, Gupta SK, McNamara P. Pharmacokinetics and absolute bioavailability of ribavirin in healthy volunteers as determined by stable-isotope methodology. Antimicrob Agents Chemother. 1999;43(10):2451–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Perronne C. Antiviral hepatitis and antiretroviral drug interactions. J Hepatol. 2006;44(1 Suppl):S119–25.

    Article  CAS  PubMed  Google Scholar 

  95. Smith DW, Frankel LR, Mathers LH, Tang AT, Ariagno RL, Prober CG. A controlled trial of aerosolized ribavirin in infants receiving mechanical ventilation for severe respiratory syncytial virus infection. N Engl J Med. 1991;325(1):24–9.

    Article  CAS  PubMed  Google Scholar 

  96. Guerguerian AM, Gauthier M, Lebel MH, Farrell CA, Lacroix J. Ribavirin in ventilated respiratory syncytial virus bronchiolitis. A randomized, placebo-controlled trial. Am J Respir Crit Care Med. 1999;160(3):829–34.

    Article  CAS  PubMed  Google Scholar 

  97. American Academy of Pediatrics Subcommittee. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118(4):1774–93.

    Article  Google Scholar 

  98. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474–502.

    Article  PubMed  Google Scholar 

  99. Boeckh M. The challenge of respiratory virus infections in hematopoietic cell transplant recipients. Br J Haematol. 2008;143(4):455–67.

    PubMed  PubMed Central  Google Scholar 

  100. Waghmare A, Campbell AP, Xie H, Seo S, Kuypers J, Leisenring W, et al. Respiratory syncytial virus lower respiratory disease in hematopoietic cell transplant recipients: viral RNA detection in blood, antiviral treatment, and clinical outcomes. Clin Infect Dis. 2013;57(12):1731–41.

    Article  CAS  PubMed  Google Scholar 

  101. Boeckh M, Englund J, Li Y, Miller C, Cross A, Fernandez H, et al. Randomized controlled multicenter trial of aerosolized ribavirin for respiratory syncytial virus upper respiratory tract infection in hematopoietic cell transplant recipients. Clin Infect Dis. 2007;44(2):245–9.

    Article  CAS  PubMed  Google Scholar 

  102. Burrows FS, Carlos LM, Benzimra M, Marriott DJ, Havryk AP, Plit ML, et al. Oral ribavirin for respiratory syncytial virus infection after lung transplantation: Efficacy and cost-efficiency. J Heart Lung Transplant. 2015;34(7):958–62.

    Article  PubMed  Google Scholar 

  103. Gorcea CM, Tholouli E, Turner A, Saif M, Davies E, Battersby E, et al. Effective use of oral ribavirin for respiratory syncytial viral infections in allogeneic haematopoietic stem cell transplant recipients. J Hosp Infect. 2017;95(2):214–7.

    Article  CAS  PubMed  Google Scholar 

  104. Ison MG, Michaels MG. RNA respiratory viral infections in solid organ transplant recipients. Am J Transplant. 2009;9(Suppl 4):S166–72.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Liu V, Dhillon GS, Weill D. A multi-drug regimen for respiratory syncytial virus and parainfluenza virus infections in adult lung and heart-lung transplant recipients. Transpl Infect Dis. 2010;12(1):38–44.

    Article  CAS  PubMed  Google Scholar 

  106. McCurdy LH, Milstone A, Dummer S. Clinical features and outcomes of paramyxoviral infection in lung transplant recipients treated with ribavirin. J Heart Lung Transplant. 2003;22(7):745–53.

    Article  PubMed  Google Scholar 

  107. Aljabr W, Touzelet O, Pollakis G, Wu W, Munday DC, Hughes M, et al. Investigating the influence of ribavirin on human respiratory syncytial virus RNA synthesis by using a high-resolution transcriptome sequencing approach. J Virol. 2016;90(10):4876–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Jordan R, Stray K, Anderson F, Perron M, Mackman R, Miller M, et al. Analysis of GS-5806 resistance emergence in human healthy adult subjects experimentally infected with respiratory syncytial virus (RSV). IDWeek; 2015; San Diego, Abstract 1189.

    Google Scholar 

  109. Li G, De Clercq E. Current therapy for chronic hepatitis C: the role of direct-acting antivirals. Antivir Res. 2017;142:83–122.

    Article  CAS  PubMed  Google Scholar 

  110. Burgess SV, Hussaini T, Yoshida EM. Concordance of sustained virologic response at weeks 4, 12 and 24 post-treatment of hepatitis C in the era of new oral direct-acting antivirals: A concise review. Ann Hepatol. 2016;15(2):154–9.

    CAS  PubMed  Google Scholar 

  111. Simmons B, Saleem J, Heath K, Cooke GS, Hill A. Long-term treatment outcomes of patients infected with hepatitis C virus: A systematic review and meta-analysis of the survival benefit of achieving a sustained virological response. Clin Infect Dis. 2015;61(5):730–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Bagaglio S, Uberti-Foppa C, Morsica G. Resistance mechanisms in hepatitis C virus: implications for direct-acting antiviral use. Drugs. 2017;77(10):1043–55.

    Article  CAS  PubMed  Google Scholar 

  113. Cuypers L, Li G, Libin P, Piampongsant S, Vandamme AM, Theys K. Genetic diversity and selective pressure in hepatitis C virus genotypes 1–6: significance for direct-acting antiviral treatment and drug resistance. Viruses. 2015;7(9):5018–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Esposito I, Trinks J, Soriano V. Hepatitis C virus resistance to the new direct-acting antivirals. Expert Opin Drug Metab Toxicol. 2016;12(10):1197–209.

    Article  CAS  PubMed  Google Scholar 

  115. Krishnan P, Beyer J, Mistry N, Koev G, Reisch T, DeGoey D, 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(2):979–87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Krishnan P, Tripathi R, Schnell G, Reisch T, Beyer J, Irvin M, 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(9):5445–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kwo PY, Poordad F, Asatryan A, Wang S, Wyles DL, Hassanein T, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol. 2017;67(2):263–71.

    Article  CAS  PubMed  Google Scholar 

  118. Lontok E, Harrington P, Howe A, Kieffer T, Lennerstrand J, Lenz O, et al. Hepatitis C virus drug resistance-associated substitutions: state of the art summary. Hepatology. 2015;62(5):1623–32.

    Article  PubMed  Google Scholar 

  119. Patino-Galindo JA, Salvatierra K, Gonzalez-Candelas F, Lopez-Labrador FX. Comprehensive screening for naturally occurring hepatitis C virus 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(4):2402–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Pawlotsky JM, Hepatitis C. Virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology. 2016;151(1):70–86.

    Article  CAS  PubMed  Google Scholar 

  121. Sarrazin C. The importance of resistance to direct antiviral drugs in HCV infection in clinical practice. J Hepatol. 2016;64(2):486–504.

    Article  PubMed  Google Scholar 

  122. Welzel TM, Bhardwaj N, Hedskog C, Chodavarapu K, Camus G, McNally J, et al. Global epidemiology of HCV subtypes and resistance-associated substitutions evaluated by sequencing-based subtype analyses. J Hepatol. 2017 Aug;67(2):224–36.

    Article  PubMed  Google Scholar 

  123. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25):2405–16.

    Article  CAS  PubMed  Google Scholar 

  124. Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1195–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, 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(5):1008–14.

    Article  CAS  PubMed  Google Scholar 

  126. Molino S, Martin MT. Hepatitis C virus resistance testing in genotype 1: the changing role in clinical utility. Ann Pharmacother. 2017;51(9):811–6.

    Article  CAS  PubMed  Google Scholar 

  127. Kan H, Imamura M, Uchida T, Hiraga N, Hayes CN, Tsuge M, et al. Protease inhibitor resistance remains even after mutant strains become undetectable by deep sequencing. J Infect Dis. 2016;214(11):1687–94.

    Article  CAS  PubMed  Google Scholar 

  128. Bourliere M, Gordon SC, Flamm SL, Cooper CL, Ramji A, Tong M, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376(22):2134–46.

    Article  CAS  PubMed  Google Scholar 

  129. Poordad F, Felizarta F, Asatryan A, Sulkowski MS, Reindollar RW, Landis CS, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology. 2017;66(2):389–97.

    Article  CAS  PubMed  Google Scholar 

  130. Pawlotsky JM. NS5A inhibitors in the treatment of hepatitis C. J Hepatol. 2013;59(2):375–82.

    Article  CAS  PubMed  Google Scholar 

  131. Ng TI, Krishnan P, Pilot-Matias T, Kati W, Schnell G, Beyer J, et al. In Vitro antiviral activity and resistance profile of the next-generation hepatitis C virus NS5A inhibitor pibrentasvir. Antimicrob Agents Chemother. 2017;61(5):e02558-16.

    Google Scholar 

  132. Scheel TK, Rice CM. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med. 2013;19(7):837–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Feld JJ, Kowdley KV, Coakley E, Sigal S, Nelson DR, Crawford D, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370(17):1594–603.

    Article  CAS  PubMed  Google Scholar 

  134. Ferenci P, Bernstein D, Lalezari J, Cohen D, Luo Y, Cooper C, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370(21):1983–92.

    Article  PubMed  CAS  Google Scholar 

  135. Zeuzem S, Jacobson IM, Baykal T, Marinho RT, Poordad F, Bourliere M, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370(17):1604–14.

    Article  CAS  PubMed  Google Scholar 

  136. Kwo PY, Mantry PS, Coakley E, Te HS, Vargas HE, Brown R Jr, et al. An interferon-free antiviral regimen for HCV after liver transplantation. N Engl J Med. 2014;371(25):2375–82.

    Article  CAS  PubMed  Google Scholar 

  137. Levrero M, Pollicino T, Petersen J, Belloni L, Raimondo G, Dandri M. Control of cccDNA function in hepatitis B virus infection. J Hepatol. 2009;51(3):581–92.

    Article  CAS  PubMed  Google Scholar 

  138. Durantel D, Zoulim F. New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus. J Hepatol. 2016;64(1 Suppl):S117–31.

    Article  CAS  PubMed  Google Scholar 

  139. European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98.

    Article  Google Scholar 

  140. Martin P, Lau DT, Nguyen MH, Janssen HL, Dieterich DT, Peters MG, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2015 update. Clin Gastroenterol Hepatol. 2015;13(12):2071–87.

    Article  PubMed  Google Scholar 

  141. Saab S, Chen PY, Saab CE, Tong MJ. The management of hepatitis B in liver transplant recipients. Clin Liver Dis. 2016;20(4):721–36.

    Article  PubMed  Google Scholar 

  142. Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352(26):2682–95.

    Article  CAS  PubMed  Google Scholar 

  143. Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351(15):1521–31.

    Article  CAS  PubMed  Google Scholar 

  144. Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003;125(6):1714–22.

    Article  CAS  PubMed  Google Scholar 

  145. Allen MI, Deslauriers M, Andrews CW, Tipples GA, Walters KA, Tyrrell DL, et al. Identification and characterization of mutations in hepatitis B virus resistant to lamivudine. Lamivudine Clinical Investigation Group Hepatology. 1998;27(6):1670–7.

    CAS  PubMed  Google Scholar 

  146. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006;131(6):1743–51.

    Article  CAS  PubMed  Google Scholar 

  147. Nash K. Telbivudine in the treatment of chronic hepatitis B. Adv Ther. 2009;26(2):155–69.

    Article  CAS  PubMed  Google Scholar 

  148. Liaw YF, Gane E, Leung N, Zeuzem S, Wang Y, Lai CL, et al. 2-year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology. 2009;136(2):486–95.

    Article  CAS  PubMed  Google Scholar 

  149. Chan HL, Heathcote EJ, Marcellin P, Lai CL, Cho M, Moon YM, et al. Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial. Ann Intern Med. 2007;147(11):745–54.

    Article  PubMed  Google Scholar 

  150. Marcellin P, Wursthorn K, Wedemeyer H, Chuang WL, Lau G, Avila C, et al. Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy. J Hepatol. 2015;62(1):41–7.

    Article  CAS  PubMed  Google Scholar 

  151. Tenney DJ, Rose RE, Baldick CJ, Pokornowski KA, Eggers BJ, Fang J, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology. 2009;49(5):1503–14.

    Article  CAS  PubMed  Google Scholar 

  152. Walsh AW, Langley DR, Colonno RJ, Tenney DJ. Mechanistic characterization and molecular modeling of hepatitis B virus polymerase resistance to entecavir. PLoS One. 2010;5(2):e9195.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Liu Y, Corsa AC, Buti M, Cathcart AL, Flaherty JF, Miller MD, et al. No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg- patients with chronic hepatitis B after 8 years of treatment. J Viral Hepat. 2017;24(1):68–74.

    Article  CAS  PubMed  Google Scholar 

  154. Saag MS. Emtricitabine, a new antiretroviral agent with activity against HIV and hepatitis B virus. Clin Infect Dis. 2006;42(1):126–31.

    Article  CAS  PubMed  Google Scholar 

  155. Fung S, Kwan P, Fabri M, Horban A, Pelemis M, Hann HW, et al. Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study. J Hepatol. 2017;66(1):11–8.

    Article  CAS  PubMed  Google Scholar 

  156. Lim SG, Ng TM, Kung N, Krastev Z, Volfova M, Husa P, et al. A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B. Arch Intern Med. 2006;166(1):49–56.

    Article  CAS  PubMed  Google Scholar 

  157. Ray AS, Fordyce MW, Hitchcock MJ. Tenofovir alafenamide: a novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antivir Res. 2016;125:63–70.

    Article  CAS  PubMed  Google Scholar 

  158. Chan HL, Fung S, Seto WK, Chuang WL, Chen CY, Kim HJ, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1(3):185–95.

    Article  PubMed  Google Scholar 

  159. Buti M, Gane E, Seto WK, Chan HL, Chuang WL, Stepanova T, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1(3):196–206.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Oregon Health and Science University, Division of Infectious Diseases, Portland, OR, USA

    Sunwen Chou

  2. Rush University Medical Center, Department of Microbial Pathogens and Immunity, Chicago, IL, USA

    Nell S. Lurain

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Correspondence to Sunwen Chou .

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  1. Clinical Associate Professor of Medicine, Texas Tech University Health Sciences Center El Paso, Paul L. Foster School of Medicine, El Paso, TX, USA

    Amar Safdar

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Chou, S., Lurain, N.S. (2019). Antiviral Consideration for Transplantation Including Drug Resistance. In: Safdar, A. (eds) Principles and Practice of Transplant Infectious Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-9034-4_54

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