Background: Cytomegalovirus (CMV) is an opportunistic pathogen responsible for substantial morbidity after solid organ transplantation and haematopoietic stem cell transplantation. Treatment of CMV disease involves a two-pronged approach with antiviral drug treatment coupled with strategies to minimize the intensity of immune suppression.

Objectives: This narrative review examines the evidence for the current treatment of CMV disease in transplant recipients, including the use of oral antiviral drugs.

Sources: Literature search was performed on PubMed with keywords cytomegalovirus, transplantation, ganciclovir, valganciclovir, maribavir, letermovir, cidofovir, and foscarnet.

Content: Intravenous and oral valganciclovir are the standard first-line treatment of cytomegalovirus disease after transplantation. Oral maribavir has demonstrated superior efficacy and safety over CMV DNA polymerase inhibitors for the treatment of refractory or resistant CMV infection. Transplant patients with severe and life-threatening CMV disease, those with very high viral load, and patients with impaired gastrointestinal absorption should still be treated initially with intravenous antiviral drugs, including ganciclovir and foscarnet. Criteria for the safe transition from intravenous therapies to oral antiviral drugs include achieving clinical improvement and satisfactory decline in viral load. Recurrence of CMV viremia and disease is common, particularly among transplant patients who are lymphopenic and have impaired CMV-specific immunity.

Implications: Oral antiviral drugs for the treatment of CMV infection and disease in transplant recipients have improved the CMV landscape, because they reduce the cost and mitigate the inconvenience and risks related to prolonged hospitalization and the need for long-term intravascular access. However, their antiviral efficacy should be complemented by an intentional strategy of reducing the degree of immune suppression to allow for immunologic recovery that ensures durable control of CMV infection.