Mixed glycoprotein B genotypes of cytomegalovirus and immunosuppression.

Cytomegalovirus (CMV) infection remains the most significant infection affecting the outcome of solid-organ trans-plantation or hematopoietic stem cell transplantation (HSCT). CMV infection causes febrile illness and end-organ disease and has been implicated indirectly in other clinically relevant outcomes. CMV infection has been shown to reduce patient survival and graft success rates and to increase the number of bacterial and fungal infections and the total cost of care [1]. Debate continues about whether the preferred treatment is prophylactic antiviral therapy for prolonged periods in all patients after receiving a transplant or preemptive use of antiviral therapy against CMV when evidence of CMV replication is present. Both approaches, however, are effective at decreasing the incidence of CMV disease in patients who undergo solid-organ trans-plantation or HSCT [2, 3]. Antiviral pro-phylaxis has also been attributed to improvement in events indirectly associated with CMV infection, such as decreases in the rate of graft rejection and improvements in the use of in-patient medical resources [4]. The remarkable achievements associated with antiviral therapy for CMV infection have also led to the development of 2 new challenges in transplant recipients: the new syndrome of late-onset CMV disease, and infection with drug-resistant strains of CMV. Late-onset CMV disease syndrome is the result of antiviral therapy delaying but not preventing the onset of CMV disease in patients who are pre-disposed to develop it. This observation stems from clinical studies of patients who received solid-organ transplants, were treated prophylactically with antiviral therapy, and developed CMV disease after discontinuation of therapy [4, 5]. This risk is particularly high in CMV-seronegative recipients of solid-organ transplants from CMV-seropositive donors (i.e., CMV D + / R Ϫ transplant recipients); as many as 27% of such patients develop CMV disease, usually within 3–6 months after undergoing transplantation [6]. In addition, the use of high-dose methylprednisolone for immunosuppression in treating potential allograft rejection greatly increases the risk of CMV disease in solid-organ transplant recipients [6]. Late-onset CMV disease syndrome has been increasingly observed in recipients of HSCTs and occurs at a median of 169 days after transplantation in 18% of allogeneic HSCT recipients [3]. In this group, CMV disease is associated with an increase in mortality; 46% of HSCT recipients with late-onset CMV disease died, and this increased to 76% in the subgroup of patients with CMV pneu-monitis [3]. An important characteristic for success after receipt of an HSCT is recovery of CMV-specific CD4 + and …