Antiviral treatment after solid organ transplantation

We were interested to read the comprehensive systematic review by E M Hodson and colleagues (June 18, p 2105)1
but are concerned over the interpretation of the results. Specifically, the statements: “prophylaxis with antiviral medications reduces the risk of cytomegalovirus disease and associated mortality in recipients of solid-organ transplants” and “this approach should be used routinely in cytomegalovirus-positive recipients and in cytomegalovirus-negative recipients of organs positive for the virus” are not fully supported by the data presented.
Limaye and colleagues2
have shown that, although antiviral prophylaxis prevented cytomegalovirus disease in recipients of liver transplants during the prophylaxis period, a significant number of patients developed late disease once antivirals were stopped. In the study by Paya and colleagues,3
in which patients were randomised to receive 100 days of prophylaxis with oral ganciclovir three times a day or once daily valganciclovir, a quarter of the patients who developed cytomegalovirus disease in the valganciclovir group did so 6–12 months after transplantation. Late-onset disease has also been independently associated with post-transplant mortality.2
Because studies with follow-up phases as short as 3 months are included in the systematic review, one cannot draw conclusions about the risk of cytomegalovirus disease or associated mortality for the whole period that patients are known to be at risk.
Furthermore, a recommendation for routine use of prophylaxis should only be made after comparison with all alternative management approaches—a task that was outside the limited objective of the review. An alternative approach to the prevention of post-transplant cytomegalovirus disease is pre-emptive therapy (ie, administration of antiviral drugs once active surveillance has detected evidence of cytomegalovirus infection by PCR or antigenaemia laboratory assays). The use of a pre-emptive approach is supported by the findings of a randomised placebo-controlled trial.4
The incidence of late disease in transplant recipients, coupled with evidence of antiviral resistance with prolonged use of ganciclovir,5
urges caution in the use of prophylaxis. The strategy of pre-emptive therapy is an effective way of preventing cytomegalovirus disease and may not be so susceptible to these disadvantages. We believe, therefore, that the decision as to how to prevent cytomegalovirus disease in solid organ transplant recipients is currently best made locally at each transplant centre.
BC has received conference support from Menarini. PS has received honoraria, sat on advisory boards, and had conference support from Roche, Astellas, Wyeth, and Novartis Pharmaceuticals. AB has received honoraria from Roche, Astellas, and Novartis Pharmaceuticals. VE has sat on advisory boards for Roche. PG has sat on advisory boards for Bayer, Roche, GlaxoSmithKline, and Novartis Pharmaceuticals.