Treatment of ganciclovir-resistant human cytomegalovirus infection

Human cytomegalovirus (HCMV) is the most frequent cause of infectious complications after whole organ transplantation. Ganciclovir is a nucleoside analogue of guanosine, and the first antiviral drug to be effective in the treatment of cytomegalovirus disease in humans. However, prolonged or repeated courses of ganciclovir predispose to the development of viral drug resistance. The isolation of a ganciclovir-resistant virus strain was first reported in 1989. Mutations in UL97 and DNA polymerase genes may induce resistance to the drug but lack of phosphorylation seems the most frequent mechanism of resistance in vivo. Most ganciclovir-resistant HCMV strains are susceptible to the pyrophosphate analogue foscarnet, which does not require activation and blocks the viral DNA polymerase by a noncompetitive mechanism. However, HCMV strains with multiple resistance to ganciclovir and other antiviral drugs have been described.