A New Antiviral Option for CMV Prevention After Kidney Transplant

Cytomegalovirus (CMV) is among the most consequential infections affecting solid organ transplant recipients. In addition to the direct consequences of viral infection, the immunomodulatory effects of CMV predispose to other complications, including graft loss and increased rates of opportunistic infections. Although CMV-seronegative recipients of CMV-seropositive donors are at highest risk and invariably develop infection in the absence of prophylaxis, there is also substantial risk to CMV-seropositive recipients. The 2 principal strategies for the prevention of CMV after solid organ transplant are the following: universal prophylaxis, which involves administering antivirals to either all or a subset of high-risk patients based on the type of organ transplanted and serologic status for a predefined period (typically 3-12 months), and preemptive therapy, which consists of periodic monitoring and initiation of antiviral therapy on CMV DNA detection above a predefined threshold. There is controversy in the literature and consequent variation in published guidelines regarding the optimal strategy for preventing posttransplant CMV, and each has risks and benefits. For either approach, intravenous ganciclovir or its oral prodrug valganciclovir are the first-line antivirals for prevention and treatment of CMV infection. Although it is generally well-tolerated, valganciclovir (ganciclovir) can cause significant myelosuppression, leading to early cessation or dose reduction of critical posttransplant immunosuppression; antiviral resistance can also emerge, particularly among high-risk patients with prolonged drug exposure. Thus, new strategies for CMV prevention are needed.