|LETTER TO THE EDITOR
|Year : 2018 | Volume
| Issue : 2 | Page : 57-58
Cytomegalovirus prophylaxis, customization of international guidelines
Mohamed E Elrggal1, Yasser Elsayed Matter2
1 Nephrology Department, Kidney and Urology Center, Alexandria, Egypt
2 Nephrology Department, Mansoura Urology & Nephrology Center (UNC), Mansoura University, Mansoura, Egypt
|Date of Submission||12-Feb-2018|
|Date of Acceptance||03-Jul-2018|
|Date of Web Publication||4-Sep-2018|
Mohamed E Elrggal
23, Mohamed Safwat Street, Kafr-Abdo
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Elrggal ME, Matter YE. Cytomegalovirus prophylaxis, customization of international guidelines. J Egypt Soc Nephrol Transplant 2018;18:57-8
|How to cite this URL:|
Elrggal ME, Matter YE. Cytomegalovirus prophylaxis, customization of international guidelines. J Egypt Soc Nephrol Transplant [serial online] 2018 [cited 2019 May 26];18:57-8. Available from: http://www.jesnt.eg.net/text.asp?2018/18/2/57/240586
We read with interest the article titled ‘infectious diseases in renal transplantation guidelines summary’ by Buttigieg et al.  that has been published recently in the Journal of the Egyptian Society of Nephrology and Transplantation. As the Egyptian Society of Nephrology and Transplantation (ESNT) is doing its best to improve nephrology care for our patients, adoption of international guidelines to suit our available resources should ensue. A very smart beginning was to summarize international guidelines into a nice comprehensive review including the prophylaxis and treatment of all infectious diseases posttransplant.
We would like to elaborate more on the tailoring of these guidelines mainly regarding cytomegalovirus (CMV) prophylaxis. The guideline summary did not mention a role for valacyclovir in CMV prophylaxis, which is the most widely used drug in Egypt currently for CMV prophylaxis, and only recommended valganciclovir.
| Regarding efficacy|| |
Both drugs (valganciclovir and valacyclovir) are currently recommended for CMV prophylaxis in kidney transplant recipients . Valganciclovir  and valacyclovir , were compared with oral ganciclovir after solid organ transplantation; both agents were found to be comparably effective in the prevention of CMV viremia and disease.
In 2015, valacyclovir (2 g four times daily) was tested against valganciclovir (900 mg daily) for 3 months in a randomized controlled trial by Reischig et al.  on 119 kidney transplant recipients (recipient or donor CMV seropositive). Results did not show significant superiority of valganciclovir in CMV prophylaxis over valacyclovir. However, the risk of biopsy-proven acute rejection was slightly higher with valacyclovir , which was attributed to the additive immunosuppressive effect of valganciclovir. Valganciclovir was shown to reduce lymphocyte proliferation and activated T-cell count, which was not documented with valacyclovir . The increased incidence of low-grade BKV viremia in patients receiving valganciclovir prophylaxis also supports the current concepts on the effect of valganciclovir on lymphocyte functions . However, and in contrast to this study, the beneficial effect on the incidence of acute rejection in kidney transplant recipients has been related to valacyclovir prophylaxis ,,. Moreover, an earlier head-to-head comparison of valacyclovir with oral ganciclovir did not show any difference in the incidence of acute rejection . Long-term follow-up is needed to ascertain whether these differences may influence transplant outcomes, such as kidney function or graft survival .
Furthermore, a low-dose valganciclovir (450 mg/day) regimen was tested against standard 900 mg/day regimen. The high-dose regimen showed no superiority in efficacy to the low-dose regimen, despite causing more side effects and higher cost of care ,. Just like valganciclovir, a low-dose valacyclovir (3 g/day), was compared with standard high dose (8 g/day) in three retrospective trials ,, and one prospective trial  with comparable efficacy, yet lower incidence of neurotoxic effects. Thus, in low-resource settings, a low-dose valacyclovir can be used safely for CMV prophylaxis.
| Regarding the economic perspective|| |
Valacyclovir prophylaxis for CMV was associated with a significant 44% cost reduction in comparison to valganciclovir in the first year after kidney transplantation, with comparable efficacy in CMV prophylaxis . Overall CMV-related costs were significantly lower in the valacyclovir arm versus valganciclovir arm; median US dollars 3473 (3108–3745) versus 5810 (4409–6757; P<0.001) per patient, respectively. Median cost of prophylaxis in the valacyclovir group was US dollars 1729 (1527–2173) compared with 3968 (2683–4857) in the valganciclovir group (P<0.001) .
On the same hand and according to our practice, the cost of a 3-month course of valacyclovir (Valtrex, 4 g/day), which is universally used in Egypt, is much less than a 3-month course of valganciclovir (Valcyte, 950 mg/day); 6600 L.E. versus 24000 L.E. per patient, respectively. This means ∼75% cost reduction in the total budget for one patient when using 4 g valacyclovir, and so allowing proper resource allocation without disrupting efficacy or patients’ safety. A recent study in Mansoura Urology and Nephrology Center addressed this issue, and the results − which was presented in the ESOT 2017 congress (page 560, PLB092)  − showed the efficacy and safety of low-dose valganciclovir and low-dose valacyclovir in preventing CMV infection with advantage to the low-dose valacyclovir as a cost reduction strategy.
To sum up, we believe in using valganciclovir only in case of CMV-seropositive donor to CMV-seronegative recipient; otherwise, valacyclovir usage can be acceptable and recommended even in the low-dose regimen described above. National societies should ensure the availability of these drugs, encourage its use, and monitor the outcomes posttransplant to assure its efficacy and safety.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Buttigieg J, El Kossi M, Halawa A. Infectious diseases in renal transplantation; summary of guidelines. J Egypt Soc Nephrol Transplant 2017; 17:75–104. [Full text]
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; 96:333–360.
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; 4:611–620.
Reischig T, Jindra P, Mares J, Cechura M, Svecová M, Hes O et al.
Valacyclovir for cytomegalovirus prophylaxis reduces the risk of acute renal allograft rejection. Transplantation 2005; 79:317–324.
Pavlopoulou ID, Syriopoulou VP, Chelioti H, Daikos GL, Stamatiades D, Kostakis A et al.
A comparative randomised study of valacyclovir vs. oral ganciclovir for cytomegalovirus prophylaxis in renal transplant recipients. Clin Microbiol Infect 2005; 11:736–743.
Reischig T, Kacer M, Jindra P, Hes O, Lysak D, Bouda M. Randomized trial of valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus in renal transplantation. Clin J Am Soc Nephrol 2015; 10:294–304.
Reischig T, Prucha M, Sedlackova L, Lysak D, Jindra P, Bouda M et al.
Valganciclovir prophylaxis against cytomegalovirus impairs lymphocyte proliferation and activation in renal transplant recipients. Antivir Ther 2011; 16:1227–1235.
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; 8:69–77.
Lowance D, Neumayer HH, Legendre CM, Squifflet JP, Kovarik J, Brennan PJ et al.
Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N Engl J Med 1999; 340:1462–1470.
Kalil AC, Mindru C, Florescu DF. Effectiveness of Valganciclovir 900 mg versus 450 mg for cytomegalovirus prophylaxis in transplantation: direct and indirect treatment comparison meta-analysis. Clin Infect Dis 2011; 52:313–321.
Gabardi S, Asipenko N, Fleming J, Lor K, McDevitt-Potter L, Mohammed A et al.
Evaluation of low- versus high-dose valganciclovir for prevention of cytomegalovirus disease in high-risk renal transplant recipients. Transplantation 2015; 99:1499–1505.
Sund F, Wahlberg J, Eriksson BM. CMV disease in CMV-mismatched renal transplant recipients with prophylactic low dose valaciclovir. J Clin Virol 2001; 23:107–111.
Toussaint ND, Tan MB, Nicholls K, Walker RG, Cohney SJ. Low-dose valaciclovir and cytomegalovirus immunoglobulin to prevent cytomegalovirus disease in high-risk renal transplant recipients. Nephrology 2011; 16:113–117.
Sund F, Tufveson G, Döhler B, Opelz G, Eriksson B-M. Clinical outcome with low-dose valacyclovir in high-risk renal transplant recipients: a 10-year experience. Nephrol Dial Transplant 2013; 28:758–765.
Reddy SP, Handa A, Tan L, Devaney A, Hughes D, Mason P et al.
Low-dose valaciclovir prophylaxis against cytomegalovirus disease in renal transplant recipients. Transpl Int 2003; 16:726–729.
Kacer M, Kielberger L, Bouda M, Reischig T. Valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus: an economic perspective. Transpl Infect Dis 2015; 17:334–341.
Abdel-Rahman AM, Wafa EW, Atta MI, Refaie AF, Sheashaa HA, Elsawy E et al.
Posters. Transpl Int 2017; 30:390–576.