Clinical use of ganciclovir for cytomegalovirus infection and the development of drug resistance

Abstract

Cytomegalovirus (CMV) infection is extremely common in patients with advanced human immunodeficiency virus infection, in whom it can produce a variety of clinical syndromes. Ganciclovir is a guanosine analogue that selectively inhibits CMV DNA polymerase when intracellularly phosphorylated to its active form. In patients with CMV retinitis, induction therapy with ganciclovir results in high rates of clinical and virologic response; maintenance therapy is required to forestall progression of disease. Clinically relevant resistance of CMV to ganciclovir has recently been reported. Decreased phosphorylation of ganciclovir to its active form has been observed in cells infected with resistant strains, suggesting that CMV may encode a ganciclovir-phosphorylating enzyme whose function is deleted by mutation, conferring resistance. Further study is needed to establish the mechanism of resistance and to define the prevalence of resistance in the clinical setting.