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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions

Author(s): Raymund R. Razonable*

Volume 26, Issue 28, 2020

Page: [3497 - 3506] Pages: 10

DOI: 10.2174/1381612826666200531152901

Price: $65

Abstract

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

Keywords: Cytomegalovirus, valganciclovir, foscarnet, cidofovir, transplantation, ganciclovir.

« Previous
[1]
Bate SL, Dollard SC, Cannon MJ. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. Clin Infect Dis 2010; 50(11): 1439-47.
[http://dx.doi.org/10.1086/652438] [PMID: 20426575]
[2]
Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 2010; 20(4): 202-13.
[http://dx.doi.org/10.1002/rmv.655] [PMID: 20564615]
[3]
Meesing A, Razonable RR. New developments in the management of cytomegalovirus infection after transplantation. Drugs 2018; 78(11): 1085-103.
[http://dx.doi.org/10.1007/s40265-018-0943-1] [PMID: 29961185]
[4]
Razonable RR, Blumberg EA. It’s not too late: a proposal to standardize the terminology of “late-onset” cytomegalovirus infection and disease in solid organ transplant recipients. Transpl Infect Dis 2015; 17(6): 779-84.
[http://dx.doi.org/10.1111/tid.12447] [PMID: 26771688]
[5]
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 2004; 4(4): 611-20.
[http://dx.doi.org/10.1111/j.1600-6143.2004.00382.x] [PMID: 15023154]
[6]
Gane E, Saliba F, Valdecasas GJ, et al. Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group. Lancet 1997; 350(9093): 1729-33.
[http://dx.doi.org/10.1016/S0140-6736(97)05535-9] [PMID: 9413463]
[7]
Lowance D, Neumayer HH, Legendre CM, et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. N Engl J Med 1999; 340(19): 1462-70.
[http://dx.doi.org/10.1056/NEJM199905133401903] [PMID: 10320384]
[8]
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 2010; 10(5): 1228-37.
[http://dx.doi.org/10.1111/j.1600-6143.2010.03074.x] [PMID: 20353469]
[9]
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 2010; 90(12): 1427-31.
[http://dx.doi.org/10.1097/TP.0b013e3181ff1493] [PMID: 21197713]
[10]
Munoz-Price LS, Slifkin M, Ruthazer R, et al. The clinical impact of ganciclovir prophylaxis on the occurrence of bacteremia in orthotopic liver transplant recipients. Clin Infect Dis 2004; 39(9): 1293-9.
[http://dx.doi.org/10.1086/425002] [PMID: 15494905]
[11]
Snydman DR. The case for cytomegalovirus prophylaxis in solid organ transplantation. Rev Med Virol 2006; 16(5): 289-95.
[http://dx.doi.org/10.1002/rmv.514] [PMID: 16888821]
[12]
George MJ, Snydman DR, Werner BG, et al. The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland. Am J Med 1997; 103(2): 106-13.
[http://dx.doi.org/10.1016/S0002-9343(97)80021-6] [PMID: 9274893]
[13]
Walker RC, Marshall WF, Strickler JG, et al. Pretransplantation assessment of the risk of lymphoproliferative disorder. Clin Infect Dis 1995; 20(5): 1346-53.
[http://dx.doi.org/10.1093/clinids/20.5.1346] [PMID: 7620022]
[14]
Helanterä I, Lautenschlager I, Koskinen P. The risk of cytomegalovirus recurrence after kidney transplantation. Transpl Int 2011; 24(12): 1170-8.
[http://dx.doi.org/10.1111/j.1432-2277.2011.01321.x] [PMID: 21902725]
[15]
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 2008; 46(6): 840-6.
[http://dx.doi.org/10.1086/528718] [PMID: 18260785]
[16]
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 2008; 8(5): 975-83.
[http://dx.doi.org/10.1111/j.1600-6143.2007.02133.x] [PMID: 18261177]
[17]
Witzke O, Hauser IA, Bartels M, Wolf G, Wolters H, Nitschke M. Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: 1-year results of a randomized clinical trial. Transplantation 2012; 93(1): 61-8.
[http://dx.doi.org/10.1097/TP.0b013e318238dab3] [PMID: 22094954]
[18]
Zamora MR. Controversies in lung transplantation: management of cytomegalovirus infections. J Lung Transplantation: The Official Publication Of The International Society for Heart Transplantation 2002; 21: 841-9.
[http://dx.doi.org/10.1016/S1053-2498(02)00435-7]
[19]
Potena L, Valantine HA. Cytomegalovirus-associated allograft rejection in heart transplant patients. Curr Opin Infect Dis 2007; 20(4): 425-31.
[http://dx.doi.org/10.1097/QCO.0b013e328259c33b] [PMID: 17609604]
[20]
Valantine H. Cardiac allograft vasculopathy after heart transplantation: risk factors and management. J Lung Transplantation: the official publication of the International Society for Heart Transplantation 2004; 23: S187-193.
[http://dx.doi.org/10.1016/j.healun.2004.03.009]
[21]
Beam E, Lesnick T, Kremers W, Kennedy CC, Razonable RR. Cytomegalovirus disease is associated with higher all-cause mortality after lung transplantation despite extended antiviral prophylaxis. Clin Transplant 2016; 30(3): 270-8.
[http://dx.doi.org/10.1111/ctr.12686] [PMID: 26701733]
[22]
Arthurs SK, Eid AJ, Deziel PJ, et al. The impact of invasive fungal diseases on survival after lung transplantation. Clin Transplant 2010; 24(3): 341-8.
[http://dx.doi.org/10.1111/j.1399-0012.2009.01076.x] [PMID: 19712081]
[23]
Manuel O, Husain S, Kumar D, et al. Assessment of cytomegalovirus specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Nephrol Dial Transplant 2012; 56(6): 817-24.
[PMID: 23196955]
[24]
Meesing A, Razonable RR. Pharmacologic and immunologic management of cytomegalovirus infection after solid organ and hematopoietic stem cell transplantation. Expert Rev Clin Pharmacol 2018; 11(8): 773-88.
[http://dx.doi.org/10.1080/17512433.2018.1501557] [PMID: 30009675]
[25]
Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33(9) e13512
[http://dx.doi.org/10.1111/ctr.13512] [PMID: 30817026]
[26]
Manuel O, Pang XL, Humar A, Kumar D, Doucette K, Preiksaitis JK. An assessment of donor-to-recipient transmission patterns of human cytomegalovirus by analysis of viral genomic variants. J Infect Dis 2009; 199(11): 1621-8.
[http://dx.doi.org/10.1086/598952] [PMID: 19385736]
[27]
Eid AJ, Razonable RR. New developments in the management of cytomegalovirus infection after solid organ transplantation. Drugs 2010; 70(8): 965-81.
[http://dx.doi.org/10.2165/10898540-000000000-00000] [PMID: 20481654]
[28]
Fernandez-Ruiz M, Gimenez E, Vinuesa V, et al. Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment. Clin Microbiol Infect 2018; 25(3): 381.e1-10.
[PMID: 29803844]
[29]
Razonable RR. Immune-based therapies for cytomegalovirus infection. Immunotherapy 2010; 2(1): 117-30.
[http://dx.doi.org/10.2217/imt.09.82] [PMID: 20635892]
[30]
Meesing A, Abraham R, Razonable RR. Clinical correlation of cytomegalovirus infection with CMV-specific CD8+ T-Cell immune competence score and lymphocyte subsets in solid organ transplant recipients. Transplantation 2018; 103(4): 32-838.
[31]
Eid AJ, Brown RA, Arthurs SK, et al. A prospective longitudinal analysis of cytomegalovirus (CMV)-specific CD4+ and CD8+ T cells in kidney allograft recipients at risk of CMV infection. Transpl Int 2010; 23(5): 506-13.
[http://dx.doi.org/10.1111/j.1432-2277.2009.01017.x] [PMID: 19951371]
[32]
Eid AJ, Brown RA, Hogan WJ, et al. Kinetics of interferon-gamma producing cytomegalovirus (CMV)-specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation. Transplant Infect Dis: an official journal of the Transplantation Society 2009; 11: 519-28.
[33]
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 2009; 9(5): 1214-22.
[http://dx.doi.org/10.1111/j.1600-6143.2009.02618.x] [PMID: 19422346]
[34]
Kumar D, Mian M, Singer L, Humar A. An interventional study using cell-mediated immunity to personalize therapy for cytomegalovirus infection after transplantation. Am J Transplant 2017; 17(9): 2468-73.
[http://dx.doi.org/10.1111/ajt.14347] [PMID: 28500691]
[35]
Gardiner BJ, Nierenberg NE, Chow JK, Ruthazer R, Kent DM, Snydman DR. Absolute lymphocyte count: a predictor of recurrent cytomegalovirus disease in solid organ transplant recipients. Clin Infect Dis 2018; 67(9): 1395-402.
[http://dx.doi.org/10.1093/cid/ciy295] [PMID: 29635432]
[36]
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 2001; 184(11): 1461-4.
[http://dx.doi.org/10.1086/324516] [PMID: 11709790]
[37]
Palmer SM, Limaye AP, Banks M, et al. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial. Ann Intern Med 2010; 152(12): 761-9.
[http://dx.doi.org/10.7326/0003-4819-152-12-201006150-00003] [PMID: 20547904]
[38]
Beam E, Germer JJ, Lahr B, et al. Cytomegalovirus (CMV) DNA quantification in bronchoalveolar lavage fluid of immunocompromised patients with CMV pneumonia. Clin Transplant 2018; 32(1): 32.
[http://dx.doi.org/10.1111/ctr.13149] [PMID: 29112278]
[39]
Knoll BM, Hammond SP, Koo S, et al. Infections following facial composite tissue allotransplantation--single center experience and review of the literature. Am J Transplant 2013; 13(3): 770-9.
[http://dx.doi.org/10.1111/ajt.12013] [PMID: 23279299]
[40]
Razonable RR, Amer H, Mardini S. Application of a new paradigm for cytomegalovirus disease prevention in mayo clinic’s first face transplant. Mayo Clin Proc 2019; 94(1): 166-70.
[http://dx.doi.org/10.1016/j.mayocp.2018.09.017] [PMID: 30611443]
[41]
Alhefzi M, Aycart MA, Bueno EM, et al. Guillain-Barré syndrome associated with resistant cytomegalovirus infection after face transplantation. Transpl Infect Dis 2016; 18(2): 288-92.
[http://dx.doi.org/10.1111/tid.12516] [PMID: 26910286]
[42]
Ambrose T, Sharkey LM, Louis-Auguste J, et al. Cytomegalovirus infection and rates of antiviral resistance following intestinal and multivisceral transplantation. Transplant Proc 2016; 48(2): 492-6.
[http://dx.doi.org/10.1016/j.transproceed.2015.09.070] [PMID: 27109985]
[43]
Nagai S, Mangus RS, Anderson E, et al. Cytomegalovirus infection after intestinal/multivisceral transplantation: a single-center experience with 210 cases. Transplantation 2016; 100(2): 451-60.
[http://dx.doi.org/10.1097/TP.0000000000000832] [PMID: 26247555]
[44]
Timpone JG, Yimen M, Cox S, et al. Resistant cytomegalovirus in intestinal and multivisceral transplant recipients. Transpl Infect Dis 2016; 18(2): 202-9.
[http://dx.doi.org/10.1111/tid.12507] [PMID: 26853894]
[45]
Razonable RR, Hayden RT. Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation. Clin Microbiol Rev 2013; 26(4): 703-27.
[http://dx.doi.org/10.1128/CMR.00015-13] [PMID: 24092851]
[46]
Hirsch HH, Lautenschlager I, Pinsky BA, et al. An international multicenter performance analysis of cytomegalovirus load tests. Clin Infect Dis 2013; 56(3): 367-73.
[http://dx.doi.org/10.1093/cid/cis900] [PMID: 23097587]
[47]
Humar A, Gregson D, Caliendo AM, et al. Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients. Transplantation 1999; 68(9): 1305-11.
[http://dx.doi.org/10.1097/00007890-199911150-00015] [PMID: 10573068]
[48]
Emery VC, Hassan-Walker AF, Burroughs AK, Griffiths PD. Human cytomegalovirus (HCMV) replication dynamics in HCMV-naive and -experienced immunocompromised hosts. J Infect Dis 2002; 185(12): 1723-8.
[http://dx.doi.org/10.1086/340653] [PMID: 12085317]
[49]
Emery VC, Sabin CA, Cope AV, Gor D, Hassan-Walker AF, Griffiths PD. Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 2000; 355(9220): 2032-6.
[http://dx.doi.org/10.1016/S0140-6736(00)02350-3] [PMID: 10885354]
[50]
Preiksaitis JK, Hayden RT, Tong Y, et al. Are we there yet? impact of the first international standard for cytomegalovirus dna on the harmonization of results reported on plasma samples. Clin Infect Dis 2016; 63(5): 583-9.
[http://dx.doi.org/10.1093/cid/ciw370] [PMID: 27307504]
[51]
Dioverti MV, Lahr BD, Germer JJ, Yao JD, Gartner ML, Razonable RR. Comparison of Standardized Cytomegalovirus (CMV) viral load thresholds in whole blood and plasma of solid organ and hematopoietic stem cell transplant recipients with cmv infection and disease. Open Forum Infect Dis 2017; 4(3) ofx143
[http://dx.doi.org/10.1093/ofid/ofx143] [PMID: 28852681]
[52]
Tong Y, Pang XL, Mabilangan C, Preiksaitis JK. Determination of the biological form of human cytomegalovirus dna in the plasma of solid-organ transplant recipients. J Infect Dis 2017; 215(7): 1094-101.
[http://dx.doi.org/10.1093/infdis/jix069] [PMID: 28407149]
[53]
Naegele K, Lautenschlager I, Gosert R, et al. Cytomegalovirus sequence variability, amplicon length, and DNase-sensitive non-encapsidated genomes are obstacles to standardization and commutability of plasma viral load results. J Clin Virol 2018; 104: 39-47.
[http://dx.doi.org/10.1016/j.jcv.2018.04.013] [PMID: 29727833]
[54]
Natori Y, Alghamdi A, Tazari M, et al. Use of viral load as a surrogate marker in clinical studies of cytomegalovirus in solid Organ transplantation: a systematic review and meta-analysis. Clin Infect Dis 2018; 66(4): 617-31.
[http://dx.doi.org/10.1093/cid/cix793] [PMID: 29020339]
[55]
Ferreira VH, Kumar D, Humar A. Deep profiling of the CD8+ T cell compartment identifies activated cell subsets and multifunctional responses associated with control of cytomegalovirus viremia. Transplantation 2018.
[PMID: 30028417]
[56]
Griffin MD. Threading the Needle: Individualized monitoring guides the transition from cytomegalovirus prophylaxis to primary immune response in a face transplant recipient. Mayo Clin Proc 2019; 94(1): 10-2.
[http://dx.doi.org/10.1016/j.mayocp.2018.11.015] [PMID: 30611437]
[57]
Meesing A, Razonable RR. Absolute lymphocyte count thresholds: a simple, readily available tool to predict the risk of cytomegalovirus infection after transplantation. Open Forum Infect Dis 2018; 5(10) ofy230
[http://dx.doi.org/10.1093/ofid/ofy230] [PMID: 30302355]
[58]
Banas B, Steubl D, Renders L, et al. Clinical validation of a novel enzyme-linked immunosorbent spot assay-based in vitro diagnostic assay to monitor cytomegalovirus-specific cell-mediated immunity in kidney transplant recipients: a multicenter, longitudinal, prospective, observational study. Transpl Int 2018; 31(4): 436-50.
[http://dx.doi.org/10.1111/tri.13110] [PMID: 29284181]
[59]
Chanouzas D, Small A, Borrows R, Ball S. Assessment of the T-SPOT.CMV interferon-γ release assay in renal transplant recipients: A single center cohort study. PLoS One 2018; 13(3) e0193968
[http://dx.doi.org/10.1371/journal.pone.0193968] [PMID: 29558479]
[60]
Gliga S, Korth J, Krawczyk A, et al. T-Track-CMV and QuantiFERON-CMV assays for prediction of protection from CMV reactivation in kidney transplant recipients. J Clin Virol 2018; 105: 91-6.
[http://dx.doi.org/10.1016/j.jcv.2018.06.009] [PMID: 29936407]
[61]
Mihm J, Leyking S, Dirks J, et al. Immune-based guidance of foscarnet treatment duration in a transplant recipient with ganciclovir-resistant cytomegalovirus infection. J Clin Virol 2016; 82: 5-8.
[http://dx.doi.org/10.1016/j.jcv.2016.06.013] [PMID: 27389910]
[62]
Sester M, Sester U, Gärtner B, et al. Levels of virus-specific CD4 T cells correlate with cytomegalovirus control and predict virus-induced disease after renal transplantation. Transplantation 2001; 71(9): 1287-94.
[http://dx.doi.org/10.1097/00007890-200105150-00018] [PMID: 11397964]
[63]
Lúcia M, Crespo E, Melilli E, et al. Preformed frequencies of cytomegalovirus (CMV)-specific memory T and B cells identify protected CMV-sensitized individuals among seronegative kidney transplant recipients. Clin Infect Dis 2014; 59(11): 1537-45.
[http://dx.doi.org/10.1093/cid/ciu589] [PMID: 25048845]
[64]
Finlen Copeland CA, Davis WA, Snyder LD, et al. Long-term efficacy and safety of 12 months of valganciclovir prophylaxis compared with 3 months after lung transplantation: a single-center, long-term follow-up analysis from a randomized, controlled cytomegalovirus prevention trial. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2011; 30: 990-6.
[http://dx.doi.org/10.1016/j.healun.2011.02.017]
[65]
Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med 2017; 377(25): 2433-44.
[http://dx.doi.org/10.1056/NEJMoa1706640] [PMID: 29211658]
[66]
Paya CV, Wilson JA, Espy MJ, et al. Preemptive use of oral ganciclovir to prevent cytomegalovirus infection in liver transplant patients: a randomized, placebo-controlled trial. J Infect Dis 2002; 185(7): 854-60.
[http://dx.doi.org/10.1086/339449] [PMID: 11920308]
[67]
Razonable RR, van Cruijsen H, Brown RA, et al. Dynamics of cytomegalovirus replication during preemptive therapy with oral ganciclovir. J Infect Dis 2003; 187(11): 1801-8.
[http://dx.doi.org/10.1086/375194] [PMID: 12751039]
[68]
Dioverti MV, Lahr B, Razonable RR. Treatment of cytomegalovirus infection and disease pre- and post-quantitative nucleic acid test standardization: does use of a more sensitive assay lead to longer treatment duration? Clin Transplant 2016; 30(2): 154-60.
[http://dx.doi.org/10.1111/ctr.12671] [PMID: 26589482]
[69]
Lisboa LF, Asberg A, Kumar D, et al. The clinical utility of whole blood versus plasma cytomegalovirus viral load assays for monitoring therapeutic response. Transplantation 2011; 91(2): 231-6.
[http://dx.doi.org/10.1097/TP.0b013e3181ff8719] [PMID: 21048530]
[70]
Lisboa LF, Kumar D, Wilson LE, Humar A. Clinical utility of cytomegalovirus cell-mediated immunity in transplant recipients with cytomegalovirus viremia. Transplantation 2012; 93(2): 195-200.
[http://dx.doi.org/10.1097/TP.0b013e31823c1cd4] [PMID: 22179399]
[71]
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 2006; 6(9): 2134-43.
[http://dx.doi.org/10.1111/j.1600-6143.2006.01413.x] [PMID: 16780548]
[72]
Reischig T, Jindra P, Hes O, Svecová M, Klaboch J, Treska V. Valacyclovir prophylaxis versus preemptive valganciclovir therapy to prevent cytomegalovirus disease after renal transplantation. Am J Transplant 2008; 8(1): 69-77.
[PMID: 17973956]
[73]
Singh N, Winston DJ, Razonable RR, et al. Preemptive therapy versus prophylaxis for prevention of cytomegalovirus disease in high-risk donor seropositive/recipient-seronegative liver transplant recipients: a NIH-sponsored, randomized, controlled, multicenter trial. In: IDWeek. San Francisco, CA: IDSA 2018.
[74]
Kotton CN, Kumar D, Caliendo AM, et al. The third international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 2018; 102(6): 900-31.
[http://dx.doi.org/10.1097/TP.0000000000002191] [PMID: 29596116]
[75]
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 2011; 91(2): 251-5.
[http://dx.doi.org/10.1097/TP.0b013e318200b9f0] [PMID: 21099744]
[76]
Lisboa LF, Preiksaitis JK, Humar A, Kumar D. Clinical utility of molecular surveillance for cytomegalovirus after antiviral prophylaxis in high-risk solid organ transplant recipients. Transplantation 2011; 92(9): 1063-8.
[http://dx.doi.org/10.1097/TP.0b013e31822fa4b7] [PMID: 21878838]
[77]
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 2010; 89(3): 320-6.
[http://dx.doi.org/10.1097/TP.0b013e3181bc0301] [PMID: 20145523]
[78]
Wiita AP, Roubinian N, Khan Y, et al. Cytomegalovirus disease and infection in lung transplant recipients in the setting of planned indefinite valganciclovir prophylaxis. Transplant Infect Dis: an official journal of the Transplantation Society 2012; 14: 248-58.
[http://dx.doi.org/10.1111/j.1399-3062.2012.00723.x]
[79]
La Rosa C, Limaye AP, Krishnan A, Blumstein G, Longmate J, Diamond DJ. Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients. Transpl Int 2011; 24(9): 920-31.
[http://dx.doi.org/10.1111/j.1432-2277.2011.01285.x] [PMID: 21672050]
[80]
Humar A, Mazzulli T, Moussa G, et al. Clinical utility of cytomegalovirus (CMV) serology testing in high-risk CMV D+/R- transplant recipients. Am J Transplant 2005; 5(5): 1065-70.
[http://dx.doi.org/10.1111/j.1600-6143.2005.00797.x] [PMID: 15816887]
[81]
Asberg A, Humar A, Rollag H, 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.
[http://dx.doi.org/10.1111/j.1600-6143.2007.01910.x] [PMID: 17640310]
[82]
Avery RK, Arav-Boger R, Marr KA, et al. Outcomes in transplant recipients treated with foscarnet for ganciclovir-resistant or refractory cytomegalovirus infection. Transplantation 2016; 100(10): e74-80.
[http://dx.doi.org/10.1097/TP.0000000000001418] [PMID: 27495775]
[83]
Cherrier L, Nasar A, Goodlet KJ, Nailor MD, Tokman S, Chou S. Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection. Am J Transplant 2018; 18(12): 3060-4.
[http://dx.doi.org/10.1111/ajt.15135] [PMID: 30286286]
[84]
Kaul DR, Stoelben S, Cober E, et al. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246. Am J Transplant 2011; 11(5): 1079-84.
[http://dx.doi.org/10.1111/j.1600-6143.2011.03530.x] [PMID: 21521474]
[85]
Humar A, Kumar D, Boivin G, Caliendo AM. Cytomegalovirus (CMV) virus load kinetics to predict recurrent disease in solid-organ transplant patients with CMV disease. J Infect Dis 2002; 186(6): 829-33.
[http://dx.doi.org/10.1086/342601] [PMID: 12198618]
[86]
Sia IG, Wilson JA, Groettum CM, Espy MJ, Smith TF, Paya CV. Cytomegalovirus (CMV) DNA load predicts relapsing CMV infection after solid organ transplantation. J Infect Dis 2000; 181(2): 717-20.
[http://dx.doi.org/10.1086/315242] [PMID: 10669361]
[87]
Ritchie BM, Barreto JN, Barreto EF, et al. Relationship of ganciclovir therapeutic drug monitoring with clinical efficacy and patient safety. Antimicrob Agents Chemother In press
[http://dx.doi.org/10.1128/AAC.01855-18] [PMID: 30602515]
[88]
Asberg A, Humar A, Jardine AG, et al. Long-term outcomes of CMV disease treatment with valganciclovir versus IV ganciclovir in solid organ transplant recipients. Am J Transplant 2009; 9(5): 1205-13.
[http://dx.doi.org/10.1111/j.1600-6143.2009.02617.x] [PMID: 19422345]
[89]
Sullivan T, Brodginski A, Patel G, Huprikar S. The role of secondary cytomegalovirus prophylaxis for kidney and liver transplant recipients. Transplantation 2015; 99(4): 855-9.
[http://dx.doi.org/10.1097/TP.0000000000000386] [PMID: 25208322]
[90]
Gardiner BJ, Chow JK, Price LL, Nierenberg NE, Kent DM, Snydman DR. Role of secondary prophylaxis with valganciclovir in the prevention of recurrent cytomegalovirus disease in solid organ transplant recipients. Clin Infect Dis 2017; 65(12): 2000-7.
[http://dx.doi.org/10.1093/cid/cix696] [PMID: 29020220]
[91]
Eid AJ, Arthurs SK, Deziel PJ, Wilhelm MP, Razonable RR. Clinical predictors of relapse after treatment of primary gastrointestinal cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2010; 10(1): 157-61.
[http://dx.doi.org/10.1111/j.1600-6143.2009.02861.x] [PMID: 19889123]
[92]
Razonable RR, Brown RA, Espy MJ, et al. Comparative quantitation of cytomegalovirus (CMV) DNA in solid organ transplant recipients with CMV infection by using two high-throughput automated systems. J Clin Microbiol 2001; 39(12): 4472-6.
[http://dx.doi.org/10.1128/JCM.39.12.4472-4476.2001] [PMID: 11724864]
[93]
Chemaly RF, Chou S, Einsele H, et al. Definitions of resistant and refractory cytomegalovirus infection and disease in transplant recipients for use in clinical trials. Clin Infect Dis 2019; 68(8): 1420-6.
[http://dx.doi.org/10.1093/cid/ciy696] [PMID: 30137245]
[94]
Limaye AP, Raghu G, Koelle DM, Ferrenberg J, Huang ML, Boeckh M. High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy. J Infect Dis 2002; 185(1): 20-7.
[http://dx.doi.org/10.1086/338143] [PMID: 11756977]
[95]
Limaye AP, Corey L, Koelle DM, Davis CL, Boeckh M. Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants. Lancet 2000; 356(9230): 645-9.
[http://dx.doi.org/10.1016/S0140-6736(00)02607-6] [PMID: 10968438]
[96]
Young PG, Rubin J, Angarone M, et al. Ganciclovir-resistant cytomegalovirus infection in solid organ transplant recipients: a single-center retrospective cohort study. Transpl Infect Dis 2016; 18(3): 390-5.
[http://dx.doi.org/10.1111/tid.12537] [PMID: 27037651]
[97]
Lurain NS, Chou S. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 2010; 23(4): 689-712.
[http://dx.doi.org/10.1128/CMR.00009-10] [PMID: 20930070]
[98]
Hakki M, Chou S. The biology of cytomegalovirus drug resistance. Curr Opin Infect Dis 2011; 24(6): 605-11.
[http://dx.doi.org/10.1097/QCO.0b013e32834cfb58] [PMID: 22001948]
[99]
Chou S, Lurain NS, Thompson KD, Miner RC, Drew WL. Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus. J Infect Dis 2003; 188(1): 32-9.
[http://dx.doi.org/10.1086/375743] [PMID: 12825168]
[100]
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 2004; 189(9): 1615-8.
[http://dx.doi.org/10.1086/382753] [PMID: 15116297]
[101]
Boivin G, Goyette N, Farhan M, Ives J, Elston R. Incidence of cytomegalovirus UL97 and UL54 amino acid substitutions detected after 100 or 200 days of valganciclovir prophylaxis J Clin Virol: the official publication of the Pan American Society for Clinical Virology 2012; 53: 208-13.
[http://dx.doi.org/10.1016/j.jcv.2011.12.019]
[102]
Bhorade SM, Lurain NS, Jordan A, et al. Emergence of ganciclovirresistant cytomegalovirus in lung transplant recipients J Heart Lung Transplant : the official publication of the International Society for Heart Transplantation 2002; 21: 1274-82.
[http://dx.doi.org/10.1016/S1053-2498(02)00463-1]
[103]
Myhre HA, Haug Dorenberg D, Kristiansen KI, et al. Incidence and outcomes of ganciclovir-resistant cytomegalovirus infections in 1244 kidney transplant recipients. Transplantation 2011; 92(2): 217-23.
[http://dx.doi.org/10.1097/TP.0b013e31821fad25] [PMID: 21685829]
[104]
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.
[http://dx.doi.org/10.1128/JCM.00391-17] [PMID: 28446569]
[105]
Razonable RR. Drug-resistant cytomegalovirus: clinical implications of specific mutations. Curr Opin Organ Transplant 2018; 23(4): 388-94.
[http://dx.doi.org/10.1097/MOT.0000000000000541] [PMID: 29794552]
[106]
Chou S, Satterwhite LE, Ercolani RJ. New locus of drug resistance in the human cytomegalovirus ul56 gene revealed by in vitro exposure to letermovir and ganciclovir. Antimicrob Agents Chemother 2018; 62(9): 62.
[http://dx.doi.org/10.1128/AAC.00922-18] [PMID: 29914965]
[107]
Eid AJ, Arthurs SK, Deziel PJ, Wilhelm MP, Razonable RR. Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes. Clin Transplant 2008; 22(2): 162-70.
[http://dx.doi.org/10.1111/j.1399-0012.2007.00761.x] [PMID: 18339135]
[108]
Klintmalm G, Lönnqvist B, Oberg B, et al. Intravenous foscarnet for the treatment of severe cytomegalovirus infection in allograft recipients. Scand J Infect Dis 1985; 17(2): 157-63.
[http://dx.doi.org/10.3109/inf.1985.17.issue-2.06] [PMID: 2992074]
[109]
Locke TJ, Odom NJ, Tapson JS, Freeman R, McGregor CG. Successful treatment with trisodium phosphonoformate for primary cytomegalovirus infection after heart transplantation. J Heart Transplant 1987; 6(2): 120-2.
[PMID: 3040944]
[110]
Mylonakis E, Kallas WM, Fishman JA. Combination antiviral therapy for ganciclovir-resistant cytomegalovirus infection in solid-organ transplant recipients. Clin Infect Dis 2002; 34(10): 1337-41.
[http://dx.doi.org/10.1086/340101] [PMID: 11981729]
[111]
Razonable RR. Antiviral drugs for viruses other than human immunodeficiency virus. Mayo Clin Proc 2011; 86(10): 1009-26.
[http://dx.doi.org/10.4065/mcp.2011.0309] [PMID: 21964179]
[112]
Isada CM, Yen-Lieberman B, Lurain NS, et al. Clinical characteristics of 13 solid organ transplant recipients with ganciclovir-resistant cytomegalovirus infection. Transpl Infect Dis 2002; 4(4): 189-94.
[http://dx.doi.org/10.1034/j.1399-3062.2002.t01-1-02008.x] [PMID: 12535261]
[113]
Hodson EM, Jones CA, Strippoli GF, Webster AC, Craig JC. Immunoglobulins, vaccines or interferon for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev 2007; (2): CD005129
[http://dx.doi.org/10.1002/14651858.CD005129.pub2] [PMID: 17443573]
[114]
Avery RK, Marty FM, Strasfeld L, et al. Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients. Transplant Infect Dis: an official journal of the Transplantation Society 2010; 12: 489-96.
[http://dx.doi.org/10.1111/j.1399-3062.2010.00550.x]
[115]
Papanicolaou GA, Silveira FP, Langston AA, et al. Maribavir for refractory or resistant cytomegalovirus infections in hematopoietic-cell or solid-organ transplant recipients: a randomized, dose-ranging, double-blind, phase 2 study. Clin Infect Dis 2018; 68(8): 1255-64.
[PMID: 30329038]
[116]
Marty FM, Winston DJ, Rowley SD, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med 2013; 369(13): 1227-36.
[http://dx.doi.org/10.1056/NEJMoa1303688] [PMID: 24066743]
[117]
Marty FM, Winston DJ, Chemaly RF, et al. A randomized, double-blind, placebo-controlled phase 3 trial of oral brincidofovir for cytomegalovirus prophylaxis in allogeneic hematopoietic-cell transplantation. Biol Blood Marrow Transplant 2018.
[PMID: 30292744]
[118]
Avery RK, Mossad SB, Poggio E, et al. Utility of leflunomide in the treatment of complex cytomegalovirus syndromes. Transplantation 2010; 90(4): 419-26.
[http://dx.doi.org/10.1097/TP.0b013e3181e94106] [PMID: 20683281]
[119]
Wolf DG, Shimoni A, Resnick IB, et al. Human cytomegalovirus kinetics following institution of artesunate after hematopoietic stem cell transplantation. Antiviral Res 2011; 90(3): 183-6.
[http://dx.doi.org/10.1016/j.antiviral.2011.03.184] [PMID: 21443904]
[120]
Rittà M, Costa C, Solidoro P, et al. Everolimus-based immunosuppressive regimens in lung transplant recipients: impact on CMV infection. Antiviral Res 2015; 113: 19-26.
[http://dx.doi.org/10.1016/j.antiviral.2014.10.016] [PMID: 25446337]
[121]
Pascual J, Royuela A, Fernández AM, et al. Role of mTOR inhibitors for the control of viral infection in solid organ transplant recipients. Transpl Infect Dis 2016; 18(6): 819-31.
[http://dx.doi.org/10.1111/tid.12601] [PMID: 27600985]
[122]
Nashan B. Induction therapy and mTOR inhibition: minimizing calcineurin inhibitor exposure in de novo renal transplant patients. Clin Transplant 2013; 27(Suppl. 25): 16-29.
[http://dx.doi.org/10.1111/ctr.12156] [PMID: 23909498]
[123]
Mallat SG, Tanios BY, Itani HS, et al. CMV and BKPyV infections in renal transplant recipients receiving an mtor inhibitor-based regimen versus a cni-based regimen: a systematic review and meta-analysis of randomized, controlled trials. Clin J Am Soc Nephrol 2017; 12(8): 1321-36.
[http://dx.doi.org/10.2215/CJN.13221216] [PMID: 28576905]
[124]
Havenith SH, Yong SL, van Donselaar-van der Pant KA, van Lier RA, ten Berge IJ, Bemelman FJ. Everolimus-treated renal transplant recipients have a more robust CMV-specific CD8+ T-cell response compared with cyclosporine- or mycophenolate-treated patients. Transplantation 2013; 95(1): 184-91.
[http://dx.doi.org/10.1097/TP.0b013e318276a1ef] [PMID: 23222818]
[125]
van der Heiden P, Marijt E, Falkenburg F, Jedema I. Control of cytomegalovirus viremia after allogeneic stem cell transplantation: a review on CMV-specific T Cell reconstitution. Biol Blood Marrow Transplant 2018; 24(9): 1776-82.
[http://dx.doi.org/10.1016/j.bbmt.2018.03.028] [PMID: 29626514]
[126]
Withers B, Blyth E, Clancy LE, et al. Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells. Blood Adv 2017; 1(24): 2193-205.
[http://dx.doi.org/10.1182/bloodadvances.2017010223] [PMID: 29296867]
[127]
Tzannou I, Papadopoulou A, Naik S, et al. Off-the-shelf virus-specific t cells to treat bk virus, human herpesvirus 6, cytomegalovirus, epstein-barr virus, and adenovirus infections after allogeneic hematopoietic stem-cell transplantation. J Clin Oncol 2017; 35(31): 3547-57.
[http://dx.doi.org/10.1200/JCO.2017.73.0655] [PMID: 28783452]
[128]
Neuenhahn M, Albrecht J, Odendahl M, et al. Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT. Leukemia 2017; 31(10): 2161-71.
[http://dx.doi.org/10.1038/leu.2017.16] [PMID: 28090089]
[129]
Holmes-Liew CL, Holmes M, Beagley L, et al. Adoptive T-cell immunotherapy for ganciclovir-resistant CMV disease after lung transplantation. Clin Transl Immunology 2015; 4(3) e35
[http://dx.doi.org/10.1038/cti.2015.5] [PMID: 25859390]
[130]
Macesic N, Langsford D, Nicholls K, et al. Adoptive T cell immunotherapy for treatment of ganciclovir-resistant cytomegalovirus disease in a renal transplant recipient. Am J Transplant 2015; 15(3): 827-32.
[http://dx.doi.org/10.1111/ajt.13023] [PMID: 25648555]
[131]
Smith C, Beagley L, Rehan S, et al. Autologous adoptive T-cell therapy for recurrent or drug-resistant cytomegalovirus complications in solid organ transplant patients: A single-arm open-label phase I clinical trial. Clin Infect Dis 2018; 68(4): 632-40.
[132]
Griffiths PD, Stanton A, McCarrell E, et al. Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial. Lancet 2011; 377(9773): 1256-63.
[http://dx.doi.org/10.1016/S0140-6736(11)60136-0] [PMID: 21481708]
[133]
Vincenti F, Budde K, Merville P, et al. A randomized, phase 2 study of ASP0113, a DNA-based vaccine, for the prevention of CMV in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Am J Transplant 2018; 18(12): 2945-54.
[http://dx.doi.org/10.1111/ajt.14925] [PMID: 29745007]
[134]
Chou S, Marousek G, Bowlin TL. Cyclopropavir susceptibility of cytomegalovirus DNA polymerase mutants selected after antiviral drug exposure. Antimicrob Agents Chemother 2012; 56(1): 197-201.
[http://dx.doi.org/10.1128/AAC.05559-11] [PMID: 21968367]

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