Journal of The Egyptian Society of Nephrology and Transplantation

: 2018  |  Volume : 18  |  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

Correspondence Address:
Mohamed E Elrggal
23, Mohamed Safwat Street, Kafr-Abdo

How to cite this article:
Elrggal ME, Matter YE. Cytomegalovirus prophylaxis, customization of international guidelines.J Egypt Soc Nephrol Transplant 2018;18:57-58

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 Mar 20 ];18:57-58
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Full Text

We read with interest the article titled ‘infectious diseases in renal transplantation guidelines summary’ by Buttigieg et al. [1] 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 [2]. Valganciclovir [3] and valacyclovir [4],[5] 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. [6] 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 [6], 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 [7]. 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 [6]. 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 [4],[8],[9]. Moreover, an earlier head-to-head comparison of valacyclovir with oral ganciclovir did not show any difference in the incidence of acute rejection [5]. Long-term follow-up is needed to ascertain whether these differences may influence transplant outcomes, such as kidney function or graft survival [6].

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 [10],[11]. Just like valganciclovir, a low-dose valacyclovir (3 g/day), was compared with standard high dose (8 g/day) in three retrospective trials [12],[13],[14] and one prospective trial [15] 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 [16]. 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) [16].

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) [17] − 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.

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Conflicts of interest

There are no conflicts of interest.


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