Prevention and treatment of cytomegalovirus infection in organ transplant recipients

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Abstract
Cytomegalovirus (CMV) is the most common viral pathogen in organ transplant recipients. The patients at highest risk of developing CMV disease are seronegative recipients of seropositive donors, and seropositive recipients who receive antilymphocyte agents such as OKT3 and antithymocyte globulin (ATG) for induction or for rejection. There have been many trials of CMV prevention, but they are difficult to compare with one another because of variability in definitions and end points. Two modalities that have been used to prevent CMV disease are prophylaxis and preemptive therapy. In prophylaxis all patients are given an antiviral agent in order to prevent CMV disease, while in preemptive therapy (also called targeted prophylaxis) only patients who are identified as ‘high risk’ are selected for treatment. Selected trials of prophylaxis and preemptive therapy in solid‐organ recipients are reviewed. The factors to be considered in using one modality or the other are side effects from antivirals, cost of monitoring and antivirals, efficacy of the two modalities, and potential emergence of drug resistance.Sensitive tests that have been used for early diagnosis and monitoring of CMV are antigenemia and the polymerase chain reaction (PCR). Antigen pp65 is a lower matrix protein and can be detected in peripheral blood leukocytes. The sensitivity and specificity are high and vary from 89% to 100% and 92% to 96%, respectively. Currently, many authors believe that the antigenemia test is more useful than the PCR test. The antigenemia test is useful for viral monitoring as a guide for preemptive therapy after organ transplantation. Persistence of high counts of antigenemia may indicate inadequate antiviral therapy or emergence of resistance. Recurrence of positive antigenemia after treatment of CMV disease can be a sign of relapse. Transplant patients who develop resistance to antiviral drugs are usually seronegative recipients who receive an organ from a seropositive donor and have several courses of antivirals for CMV disease. Ganciclovir is the most frequent antiviral agent used in transplant recipients and is usually well tolerated. Resistance to ganciclovir may occur and is usually secondary to virus mutation in the UL97 gene. The availability of sensitive diagnostic tests such as pp65 antigenemia has made the early diagnosis of CMV possible in organ transplant recipients. CMV is being treated much earlier now, and progression to disseminated disease is uncommon. Prudent use of antiviral drugs will hopefully limit the problem of drug resistance.