Valganciclovir for the treatment of cytomegalovirus retinitis in patients with AIDS

Cytomegalovirus (CMV) retinitis is a sight-threatening illness that results from the reactivation of CMV in the retina of patients with end-stage AIDS. Valganciclovir, a prodrug of ganciclovir, is indicated as induction therapy at a dose of 900 mg twice daily for 3 weeks, and maintenance therapy at a dose of 900 mg once daily for CMV retinitis in patients with AIDS. After oral administration, valganciclovir is rapidly absorbed and extensively hydrolyzed to ganciclovir by intestinal and hepatic esterase enzymes. The bioavailability of ganciclovir after oral administration of valganciclovir is tenfold higher than oral ganciclovir. At a dose of 900 mg once daily, valganciclovir provides systemic exposure of ganciclovir comparable to intravenous ganciclovir (5 mg/kg daily). The most common adverse events of valganciclovir are myelosuppression and gastrointestinal symptoms. Prolonged valganciclovir administration could lead to the emergence of ganciclovir-resistant CMV. The use of highly active antiretroviral therapy (HAART) for the treatment of underlying HIV infection has led to the significant decline in the incidence and improvement in the outcome of CMV retinitis in patients with AIDS. Among patients on HAART, it is now possible to discontinue what was once considered as lifelong CMV-specific therapy. In particular, among patients with a CD4⁺ T-lymphocyte count over 100 cells/µl for at least 6 months, maintenance valganciclovir therapy may be safely discontinued. In this article, the management of CMV retinitis in patients with AIDS is discussed, with specific emphasis on the role of valganciclovir in the therapeutic arsenal.