Efficacy of low-dose valganciclovir in Cytomegalovirus R+ lung transplant recipients: a retrospective comparative analysis
Background: Cytomegalovirus (CMV) infection is extremely common after lung transplant and can be associated with significant morbidity and mortality. Current practice suggests the use of 900 mg daily of valganciclovir for CMV prophylaxis, but there is no literature assessing whether 450 mg daily of valganciclovir is sufficient in intermediate CMV risk lung transplant recipients. Therefore, we sought to assess the role of low-dose valganciclovir (LDV) versus high-dose valganciclovir (HDV) prophylaxis in intermediate-risk (R+) recipients.
Methods: We conducted a retrospective analysis on lung transplant recipients at the Norton Thoracic Institute in Phoenix, Arizona looking at intermediate-risk patients that received either valganciclovir 450 mg per day (LDV) or 900 mg/day (HDV). All patients were followed for 1 year posttransplant for incidence of CMV viremia. The primary outcome was the rate of CMV viremia as determined by a positive CMV polymerase chain reaction ([PCR] >2.7 log copies/mL). Secondary outcomes included rate of adverse events, acute cellular rejection, and mortality.
Results: The primary analysis included 103 patients (55 in the LDV group, 48 in the HDV group). In the LDV group, 9 patients (16.4%) developed CMV viremia compared to 4 (8.3%) in the HDV group (p=0.221) with no difference observed in adverse event rates between groups.
Conclusion: There was no statistical difference between groups for the primary outcome. However, the effect size demonstrated in this analysis may be of clinical relevance and valganciclovir 450 mg daily would not be recommended in intermediate risk lung transplant recipients at this time. To confirm our results, further prospective studies enrolling larger patient populations are necessary.
Avidan Y, Paul M, Rahamimov R, Bishara J, Samra Z, Edna S, et al. Selective low-dose valganciclovir for prevention of cytomegalovirus disease following kidney transplantation. J Infect 2008;57:236-40. DOI: https://doi.org/10.1016/j.jinf.2008.06.016
Kotton C, Kumar D, Caliendo A, Huprikar S, Chou S, Danziger-Isakov L, et al. The Third International Consensus Guidelines on the Management of cytomegalovirus in solid-organ transplantation. Transplantation 2018;102:900-31. DOI: https://doi.org/10.1097/TP.0000000000002191
Razonable R, Humar A. Cytomegalovirus in solid organ transplantation. Am J Transplant 2013;13:s93-106. DOI: https://doi.org/10.1111/ajt.12103
Finlen Copeland C, Davis W, Snyder L, Banks M, Avery R, Davis R, 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. J Heart Lung Transpl 2011;30:990-6. DOI: https://doi.org/10.1016/j.healun.2011.02.017
Humar A, Kumar D, Preiksaitis J, Boivin G, Siegal D, Fenton J, et al. A trial of valganciclovir prophylaxis for cytomegalovirus prevention in lung transplant recipients. Am J Transplant 2005;5:1462-8. DOI: https://doi.org/10.1111/j.1600-6143.2005.00866.x
Jaksch P, Zweytick B, Kerschner H, Hoda A, Keplinger M, Lang G, et al. Cytomegalovirus prevention in high-risk lung transplant recipients: Comparison of 3- vs 12-month valganciclovir therapy. J Heart Lung Transplant 2009;28:670-5. DOI: https://doi.org/10.1016/j.healun.2009.03.012
Palmer S, Limaye A, Banks M, Gallup D, Chapman J, Lawrence E et al. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation. Ann of Intern Med 2010;152:761. DOI: https://doi.org/10.7326/0003-4819-152-12-201006150-00003
Zamora M, Nicolls M, Hodges T, Marquesen J, Astor T, Grazia T, et al. Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation. Am J Transplant 2004;4:1635-42. DOI: https://doi.org/10.1111/j.1600-6143.2004.00571.x
Chamberlain C, Penzak S, Alfaro R, Wesley R, Daniels C, Hale D, et al. Pharmacokinetics of low and maintenance dose valganciclovir in kidney transplant recipients. Am J Transplant 2008;8:1297-302. DOI: https://doi.org/10.1111/j.1600-6143.2008.02220.x
Heldenbrand S, Li C, Cross R, DePiero K, Dick T, Ferguson K, et al. Multicenter evaluation of efficacy and safety of low-dose versus high-dose valganciclovir for prevention of cytomegalovirus disease in donor and recipient positive (D+/R+) renal transplant recipients. Transpl Infect Dis 2016;18:904-12. DOI: https://doi.org/10.1111/tid.12609
Khan S, Sullivan T, Ali M, Dunn D, Patel G, Huprikar S. Low-dose valganciclovir for cytomegalovirus prophylaxis in intermediate-risk liver transplantation recipients. Liver Transpl 2018;24:616-2. DOI: https://doi.org/10.1002/lt.25047
Le Page A, Jager M, Kotton C, Simoons-Smit A, Rawlinson W. International survey of cytomegalovirus management in solid organ transplantation after the publication of consensus guidelines. Transplantation 2013;95:1455-60. DOI: https://doi.org/10.1097/TP.0b013e31828ee12e
Stevens D, Sawinski D, Blumberg E, Galanakis N, Bloom R, Trofe-Clark J. Increased risk of breakthrough infection among cytomegalovirus donor-positive/recipient-negative kidney transplant recipients receiving lower-dose valganciclovir prophylaxis. Transpl Infect Dis 2015;17:163-73. DOI: https://doi.org/10.1111/tid.12349
Azevedo L, Pierrotti L, Abdala E, Costa S, Strabelli T, Campos S et al. Cytomegalovirus infection in transplant recipients. Clinics 2015;70:515-23. DOI: https://doi.org/10.6061/clinics/2015(07)09
Eid A, Arthurs S, Deziel P, Wilhelm M, Razonable R. Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes. Clin Transplant 2007;22:162-70. DOI: https://doi.org/10.1111/j.1399-0012.2007.00761.x
Egan T, Edwards L. Effect of the lung allocation score on lung transplantation in the United States. J Heart Lung Transplant 2016;35:433-9. DOI: https://doi.org/10.1016/j.healun.2016.01.010
Kruger R, Paranjothi S, Storch G, Lynch J, Trulock E. Impact of prophylaxis with cytogam alone on the incidence of CMV viremia in CMV-seropositive lung transplant recipients. J Heart Lung Transplant 2003;22:754-63. DOI: https://doi.org/10.1016/S1053-2498(02)00648-4
Rea F, Potena L, Yonan N, Wagner F, Calabrese F. Cytomegalovirus hyper immunoglobulin for CMV prophylaxis in thoracic transplantation. Transplantation 2016;100:S19-26. DOI: https://doi.org/10.1097/TP.0000000000001096
Aguado J, Gomez-Sanchez M, Lumbreras C, Delgado J, Lizasoain M, Otero J, et al. Prospective randomized trial of efficacy of ganciclovir versus that of anti-cytomegalovirus (CMV) immunoglobulin to prevent CMV disease in CMV- seropositive heart transplant recipients treated with OKT3. Antimicrob Agents Chemother 1995;39:1643-5. DOI: https://doi.org/10.1128/AAC.39.7.1643
- Abstract views: 999
- PDF: 53
- HTML: 0
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.