Eficacia y seguridad de ganciclovir y valganciclovir en el manejo de la infección por citomegalovirus en el trasplante de órgano sólido

Abstract

Cytomegalovirus (CMV) is the most important viral pathogen in solid organ transplant (SOT) recipients. Recommendations for infection prophylaxis and treatment with ganciclovir (GCV) or valganciclovir (VGCV) are described in recent guidelines. However, the optimal duration of primary CMV prophylaxis and the role of secondary prophylaxis remain unclear. Moreover, risk factors for late CMV infection and for infection relapse are not well known. We reviewed all cases of SOT patients who received either primary CMV prophylaxis or treatment of CMV infection with GCV and/or VGCV at our institution over a seven year period in order to determine the efficacy and safety of therapy. We investigated potential risk factors for late CMV infection and relapse and we also looked through CMV indirect effects to determine wether extended primary prophylaxis and secondary prophylaxis were associated with lower rates of acute rejection, graft loss or improved patient survival. One hundred and seventy out of 438 recipients of one or more SOT during the study period were included in the study. Sixty patients received primary CMV prophylaxis for a mean of 122 days. Sixteen (26,7%) patients were diagnosed with CMV infection after the cessation of prophylaxis and 6 (10%) were diagnosed with CMV disease. CMV seronegative serostatus and the age of the recipient were associated with an increased risk of CMV late infection. Extended primary prophylaxis over 100 days was not associated with lower rates of CMV infection. One hundred and twenty six patients received GCV and/or VGCV for the treatment of CMV infection, and 103 (83,1%) patients received secondary prophylaxis after treatment. Relapsed CMV infection (39,5%) occurred more often among CMV seronegative recipients and initial median CMV viral load was significantly higher in those who relapsed. The use of secondary prophylaxis was not associated with fewer relapses. However, secondary prophylaxis was associated with a reduction in acute rejection rate and improved patient survival. Hematological toxicity occurred in 40% of the patients during primary prophylaxis and in 45% of them during treatment. Duration of antiviral prophylaxis was significantly longer in those with toxicity. Liver transplant recipients had a higher risk of hematological disturbances during CMV treatment compared to kidney and heart transplant recipients. Other factors independently associated with toxicity were the treatment duration and the use of high dose of antivirals.