Advances in cytomegalovirus-preventive strategies in solid organ transplantation: Defending pre-emptive therapy

Expert Review of Anti-Infective Therapy

Volumn 10, Issue 1, 2012, Pages 51-61

  Reischig, Tomáš ^a  

^a CHARLES UNIVERSITY   (Czech Republic)

Author keywords

CMV specific T cell immunity; cytomegalovirus; organ transplantation; pre emptive therapy; prophylaxis; valacyclovir; valganciclovir

Indexed keywords

ANTIVIRUS AGENT; CYTOMEGALOVIRUS ANTIBODY; GANCICLOVIR; MESSENGER RNA; VALACICLOVIR; VALGANCICLOVIR;

ACUTE GRAFT REJECTION; ANTIVIRAL RESISTANCE; CELLULAR IMMUNITY; CLINICAL PRACTICE; COMBINATION CHEMOTHERAPY; COST OF ILLNESS; CYTOMEGALOVIRUS INFECTION; DISEASE SURVEILLANCE; DOSE RESPONSE; DRUG EFFECT; DRUG MEGADOSE; DRUG WITHDRAWAL; EVIDENCE BASED MEDICINE; GRAFT FAILURE; GRAFT SURVIVAL; HUMAN; HUMAN CYTOMEGALOVIRUS; IMMUNE DEFICIENCY; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOSUPPRESSIVE TREATMENT; INFECTION PREVENTION; INFECTION RISK; LEUKOPENIA; MONOTHERAPY; NEUTROPENIA; NONHUMAN; ORGAN TRANSPLANTATION; PATIENT MONITORING; POLYMERASE CHAIN REACTION; REVIEW; RISK REDUCTION; SEROLOGY; T LYMPHOCYTE ACTIVATION; TREATMENT DURATION; VIREMIA; VIRUS LOAD;

ACYCLOVIR; ANTIVIRAL AGENTS; CLINICAL PROTOCOLS; CYTOMEGALOVIRUS INFECTIONS; GANCICLOVIR; HUMANS; IMMUNOSUPPRESSIVE AGENTS; OPPORTUNISTIC INFECTIONS; ORGAN TRANSPLANTATION; RANDOMIZED CONTROLLED TRIALS AS TOPIC; VALINE;

EID: 83455217692     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/eri.11.156     Document Type: Review

References (62)

1. Kotton CN. Management of cytomegalovirus infection in solid organ transplantation. Nat. Rev. Nephrol. 6(12), 711-721 (2011).
2. Baron C, Forconi C, Lebranchu Y. Revisiting the effects of CMV on long-term transplant outcome. Curr. Opin. Organ Transplant. 15(4), 492-498 (2010).
3. Sagedal S, Nordal KP, Hartmann A, et al. The impact of cytomegalovirus infection and disease on rejection episodes in renal allograft recipients. Am. J. Transplant. 2(9), 850-856 (2002).
4. Reischig T, Jindra P, Svecova M, Kormunda S, Opatrny K Jr, Treska V. The impact of cytomegalovirus disease and asymptomatic infection on acute renal allograft rejection. J. Clin. Virol. 36(2), 146-151 (2006).
5. Reischig T, Jindra P, Hes O, Bouda M, Kormunda S, Treska V. Effect of cytomegalovirus viremia on subclinical rejection or interstitial fibrosis and tubular atrophy in protocol biopsy at 3 months in renal allograft recipients managed by preemptive therapy or antiviral prophylaxis. Transplantation 87(3), 436-444 (2009).
6. Smith JM, Corey L, Bittner R, et al. Subclinical viremia increases risk for chronic allograft injury in pediatric renal transplantation. J. Am. Soc. Nephrol. 21(9), 1579-1586 (2010).
7. Sagedal S, Hartmann A, Nordal KP, et al. Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival. Kidney Int. 66(1), 329-337 (2004).
8. Reischig T. Cytomegalovirus-associated renal allograft rejection: new challenges for antiviral preventive strategies. Expert Rev. Anti Infect. Ther. 8(8), 903-910 (2010).
9. Opelz G, Dohler B, Ruhenstroth A. Cytomegalovirus prophylaxis and graft outcome in solid organ transplantation: a collaborative transplant study report. Am. J. Transplant. 4(6), 928-936 (2004).
10. Kotton CN, Kumar D, Caliendo AM, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation 89(7), 779-795 (2010).
11. Paya C, Humar A, Dominguez E, et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am. J. Transplant. 4(4), 611-620 (2004).
12. Humar A, Lebranchu Y, Vincenti F, et al. The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am. J. Transplant. 10(5), 1228-1237 (2010).
13. Humar A, Limaye AP, Blumberg EA, et al. Extended valganciclovir prophylaxis in D+/R-kidney transplant recipients is associated with long-term reduction in cytomegalovirus disease: two-year results of the IMPACT study. Transplantation 90(12), 1427-1431 (2010).
14. Lowance D, Neumayer HH, Legendre CM, et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N. Engl. J. Med. 340(19), 1462-1470 (1999).
15. Reischig T, Jindra P, Mares J, et al. Valacyclovir for cytomegalovirus prophylaxis reduces the risk of acute renal allograft rejection. Transplantation 79(3), 317-324 (2005).
16. Singh N, Wannstedt C, Keyes L, Wagener MM, Gayowski T, Cacciarelli TV. Indirect outcomes associated with cytomegalovirus (opportunistic infections, hepatitis C virus sequelae, and mortality) in liver-transplant recipients with the use of preemptive therapy for 13 years. Transplantation 79(10), 1428-1434 (2005).
17. Kalil AC, Levitsky J, Lyden E, Stoner J, Freifeld AG. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann. Intern. Med. 143(12), 870-880 (2005).
18. Shibata D, Martin WJ, Appleman MD, Causey DM, Leedom JM, Arnheim N. Detection of cytomegalovirus DNA in peripheral blood of patients infected with human immunodeficiency virus. J. Infect. Dis. 158(6), 1185-1192 (1988).
19. Blok MJ, Christiaans MH, Goossens VJ, et al. Evaluation of a new method for early detection of active cytomegalovirus infections. A study in kidney transplant recipients. Transpl. Int. 11(Suppl. 1), S107-S109 (1998).
20. Li H, Dummer JS, Estes WR, Meng S, Wright PF, Tang YW. Measurement of human cytomegalovirus loads by quantitative real-time PCR for monitoring clinical intervention in transplant recipients. J. Clin. Microbiol. 41(1), 187-191 (2003).
21. Pang XL, Fox JD, Fenton JM, Miller GG, Caliendo AM, Preiksaitis JK. Interlaboratory comparison of cytomegalovirus viral load assays. Am. J. Transplant. 9(2), 258-268 (2009).
22. Ruttmann E, Geltner C, Bucher B, et al. Combined CMV prophylaxis improves outcome and reduces the risk for bronchiolitis obliterans syndrome (BOS) after lung transplantation. Transplantation 81(10), 1415-1420 (2006).
23. Potena L, Holweg CT, Chin C, et al. Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation 82(3), 398-405 (2006).
24. Khoury JA, Storch GA, Bohl DL, et al. Prophylactic versus preemptive oral valganciclovir for the management of cytomegalovirus infection in adult renal transplant recipients. Am. J. Transplant. 6(9), 2134-2143 (2006).
25. Reischig T, Jindra P, Hes O, Svecova M, Klaboch J, Treska V. Valacyclovir prophylaxis versus preemptive valganciclovir therapy to prevent cytomegalovirus disease after renal transplantation. Am. J. Transplant. 8(1), 69-77 (2008).
26. Sun HY, Wagener MM, Singh N. Prevention of posttransplant cytomegalovirus disease and related outcomes with valganciclovir: a systematic review. Am. J. Transplant. 8(10), 2111-2118 (2008).
27. Limaye AP, Bakthavatsalam R, Kim HW, et al. Impact of cytomegalovirus in organ transplant recipients in the era of antiviral prophylaxis. Transplantation 81(12), 1645-1652 (2006).
28. Kalil AC, Freifeld AG, Lyden ER, Stoner JA. Valganciclovir for cytomegalovirus prevention in solid organ transplant patients: an evidence-based reassessment of safety and efficacy. PLoS ONE 4(5), e5512 (2009).
29. Razonable RR, Rivero A, Rodriguez A, et al. Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir. J. Infect. Dis. 184(11), 1461-1464 (2001).
30. Arthurs SK, Eid AJ, Pedersen RA, et al. Delayed-onset primary cytomegalovirus disease and the risk of allograft failure and mortality after kidney transplantation. Clin. Infect. Dis. 46(6), 840-846 (2008).
31. Freeman RB, Paya C, Pescovitz MD, et al. Risk factors for cytomegalovirus viremia and disease developing after prophylaxis in high-risk solid-organ transplant recipients. Transplantation 78(12), 1765-1773 (2004).
32. Blumberg EA, Hauser IA, Stanisic S, et al. Prolonged prophylaxis with valganciclovir is cost effective in reducing posttransplant cytomegalovirus disease within the United States. Transplantation 90(12), 1420-1426 (2010).
33. Kliem V, Fricke L, Wollbrink T, Burg M, Radermacher J, Rohde F. Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial. Am. J. Transplant. 8(5), 975-983 (2008).
34. Spinner ML, Saab G, Casabar E, Bowman LJ, Storch GA, Brennan DC. Impact of prophylactic versus preemptive valganciclovir on long-term renal allograft outcomes. Transplantation 90(4), 412-418 (2010).
35. Boillat Blanco N, Pascual M, Venetz JP, Nseir G, Meylan PR, Manuel O. Impact of a preemptive strategy after 3 months of valganciclovir cytomegalovirus prophylaxis in kidney transplant recipients. Transplantation 91(2), 251-255 (2011).
36. van der Beek MT, Berger SP, Vossen AC, et al. Preemptive versus sequential prophylactic-preemptive treatment regimens for cytomegalovirus in renal transplantation: comparison of treatment failure and antiviral resistance. Transplantation 89(3), 320-326 (2010).
37. Kumar D, Chernenko S, Moussa G, et al. Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients. Am. J. Transplant. 9(5), 1214-1222 (2009).
38. Weclawiak H, Kamar N, Mengelle C, et al. Pre-emptive intravenous ganciclovir versus valganciclovir prophylaxis for de novo cytomegalovirus- seropositive kidney-transplant recipients. Transpl. Int. 23(10), 1056-1064 (2010).
39. Gerna G, Lilleri D, Fornara C, et al. Monitoring of human cytomegalovirus-specific CD4 and CD8 T-cell immunity in patients receiving solid organ transplantation. Am. J. Transplant. 6(10), 2356-2364 (2006).
40. Nebbia G, Mattes FM, Smith C, et al. Polyfunctional cytomegalovirus- specific CD4+ and pp65 CD8+ T cells protect against high-level replication after liver transplantation. Am. J. Transplant. 8(12), 2590-2599 (2008).
41. Egli A, Binet I, Binggeli S, et al. Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients. J. Transl. Med. 6, 29 (2008).
42. Mattes FM, Vargas A, Kopycinski J, et al. Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation. Am. J. Transplant. 8(5), 990-999 (2008).
43. La Rosa C, Limaye AP, Krishnan A, Longmate J, Diamond DJ. Longitudinal assessment of cytomegalovirus (CMV)-specific immune responses in liver transplant recipients at high risk for late CMV disease. J. Infect. Dis. 195(5), 633-644 (2007).
44. Tu W, Potena L, Stepick-Biek P, et al. T-cell immunity to subclinical cytomegalovirus infection reduces cardiac allograft disease. Circulation 114(15), 1608-1615 (2006).
45. Nickel P, Bold G, Presber F, et al. High levels of CMV-IE-1-specific memory T cells are associated with less alloimmunity and improved renal allograft function. Transpl. Immunol. 20(4), 238-242 (2009).
46. Singh N. Prevention of cytomegalovirus in organ transplant recipients: cross roads between antiviral and antitumor immunity. Transplantation 90(4), 360-361 (2010).
47. Soderberg-Naucler C. Protection from cancer in kidney transplant patients by gammadelta T cells: role of CMV infection? J. Am. Soc. Nephrol. 21(1), 11-13 (2010).
48. Couzi L, Levaillant Y, Jamai A, et al. Cytomegalovirus-induced gd T cells associate with reduced cancer risk after kidney transplantation. J. Am. Soc. Nephrol. 21(1), 181-188 (2010).
49. Abate D, Saldan A, Fiscon M, et al. Evaluation of cytomegalovirus (CMV)-specific T cell immune reconstitution revealed that baseline antiviral immunity, prophylaxis, or preemptive therapy but not antithymocyte globulin treatment contribute to CMV-specific T cell reconstitution in kidney transplant recipients. J. Infect. Dis. 202(4), 585-594 (2010).
50. Benmarzouk-Hidalgo OJ, Cisneros JM, Cordero E, et al. Therapeutic effect of the acquisition of cytomegalovirus-specific immune response during preemptive treatment. Transplantation 91(8), 927-933 (2011).
51. Singh N. Unraveling the biologic basis of late-onset cytomegalovirus disease in high-risk organ transplant recipients. Transplantation 91(8), 825-826 (2011).
52. Heagy W, Crumpacker C, Lopez PA, Finberg RW. Inhibition of immune functions by antiviral drugs. J. Clin. Invest. 87(6), 1916-1924 (1991).
53. Bowden RA, Digel J, Reed EC, Meyers JD. Immunosuppressive effects of ganciclovir on in vitro lymphocyte responses. J. Infect. Dis. 156(6), 899-903 (1987).
54. Battiwalla M, Wu Y, Bajwa RP, et al. Ganciclovir inhibits lymphocyte proliferation by impairing DNA synthesis. Biol. Blood Marrow Transplant 13(7), 765-770 (2007).
55. Reischig T, Prucha M, Sedlackova L, et al. Valganciclovir prophylaxis against cytomegalovirus impairs lymphocyte proliferation and activation in renal transplant recipients. Antivir. Ther. doi:10.3851/IPM1879 (2011) (Epub ahead of print).
56. Hodson EM, Jones CA, Webster AC, et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials. Lancet 365(9477), 2105-2115 (2005).
57. Reischig T, Hribova P, Jindra P, et al. Improved long-term renal allograft survival in preemptive valganciclovir therapy compared with valacyclovir prophylaxis for cytomegalovirus: results of randomized controlled trial. Am. J. Transplant, 11(Suppl. 2), S455 (2011).
58. Reischig T, Nemcova J, Vanecek T, et al. Intragraft cytomegalovirus infection: a randomized trial of valacyclovir prophylaxis versus pre-emptive therapy in renal transplant recipients. Antivir. Ther. 15(1), 23-30 (2010).
59. Boivin G, Goyette N, Gilbert C, et al. Absence of cytomegalovirus- resistance mutations after valganciclovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients. J. Infect. Dis. 189(9), 1615-1618 (2004).
60. Myhre HA, Haug Dorenberg D, Kristiansen KI, et al. Incidence and outcomes of ganciclovir-resistant cytomegalovirus infections in 1244 kidney transplant recipients. Transplantation 92(2), 217-223 (2011).
61. Couzi L, Helou S, Bachelet T, et al. High incidence of anticytomegalovirus drug resistance among D+R-kidney transplant recipients receiving preemptive therapy. Am. J. Transplant. doi: 10.1111/j.1600-6143.2011. 03766.x (2011) (Epub ahead of print).
62. Hurst FP, Belur P, Nee R, et al. Poor outcomes associated with neutropenia after kidney transplantation: analysis of United States Renal Data System. Transplantation 92(1), 36-40 (2011).