A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R)) solid organ transplant recipients The rate of cytomegalovirus (CMV) disease in solid organ transplant (SOT) recipients who are CMV seronegative with a seropositive donor (D+/R)) can be as high as 55% without prophylaxis (1). Long-term prophylaxis either with oral ganciclovir or valganciclovir effectively reduces the incidence and severity of CMV disease in these high-risk patients (2, 3), but such strategy poses an increased risk of late-CMV disease occurring after prophylaxis withdrawal (4–6), which has been related with a worse prognosis of CMV disease and also with an increased global mortality of affected patients (7). A plausible hypothesis for this phenomenon could reside in the lack of exposure of the recipient to CMV when effective prophylaxis is administered promptly, which could impair the development of an adequate CMV-specific response of cytotoxic and helper T lymphocytes that seems to be crucial in the protection against CMV disease after CMV primary infection (8–10). The aim of this study was to evaluate a new strategy of delayed CMV prophylaxis that allows a transitory exposure of the immune system to CMV, which could let to mount an adequate CMV-specific cytotoxic response in (D+/R)) San Juan R, Yebra M, Lumbreras C, Lo´pez-Medrano F, Lizasoain M, Meneu JC, Delgado J, Andre´s A, Aguado JM. A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R)) solid organ transplant recipients. Clin Transplant 2009: 23: 666–671. ª 2009 John Wiley & Sons A/S. Abstract: Long-term prophylaxis against cytomegalovirus (CMV) started immediately after transplantation in (D+/R)) poses a higher risk of late- onset CMV disease. Delayed CMV prophylaxis could allow a transitory exposure of the immune system to CMV, which would let the immune system mount an adequate CMV-specific cytotoxic response in (D+/R)) patients and confer protection against CMV disease. We included all (D+/ R)) solid organ transplant recipients (SOT) performed at our institution (January 3/October 6) who received CMV prophylaxis (mainly with oral valganciclovir) during 100 d. In the first period (until December 4), prophylaxis was initiated immediately after transplantation (conventional prophylaxis: CP). Since January 5, it was initiated after 14 d (delayed prophylaxis: DP). Incidence and severity of CMV disease was compared between both groups. A total of 44 SOT recipients were included (CP: 26 and DP: 18). CMV disease was diagnosed in eight patients (18%), seven of 26 (27%) in the CP group, and one of 18 (5.5%) in the DP group (p = 0.07). CMV colitis was reported in five of 26 patients in the CP group (19%), whereas there were no cases of visceral CMV disease in the DP group (p = 0.048). A 14-d delay in the beginning of long-term prophylaxis against CMV in (D+/R)) is safe and could prevent the onset of late-CMV disease. R. San Juan a , M. Yebra a , C. Lumbreras a , F. Lo ´ pez-Medrano a , M. Lizasoain a , J.C. Meneu b , J. Delgado c , A. Andre ´s d and J.M. Aguado a a Unit of Infectious Diseases, b Surgery and Abdominal Transplantation, c Cardiology Department and d Renal Transplantation and Nephrology Department, Hospital Universitario ‘‘Doce de Octubre,’’ Universidad Complutense, Madrid, Spain Key words: cytomegalovirus disease – D+/R) – delayed – prophylaxis – transplantation Corresponding author: Rafael San Juan Garrido MD, Infectious Diseases Unit, Hospital Univer- sitario 12 de Octubre, Carretera de Andalucı ´a Km 5,4, 28041 Madrid, Spain. Tel.: 0034 913908000 (ext. 1712); fax: 0034 914695775; e-mail: rafasjg@yahoo.es Accepted for publication 7 July 2009 Clin Transplant 2009: 23: 666–671 DOI: 10.1111/j.1399-0012.2009.01077.x ª 2009 John Wiley & Sons A/S. 666