Cidofovir is a potent, broad spectrum antiviral agent with activity in
vitro and in vivo against cytomegalovirus and other members of the he
rpesvirus family, as well as certain other DNA viruses. After uptake i
nto cells it is converted enzymatically to cidofovir diphosphate, a st
ructural analogue of deoxycytidine triphosphate, which selectively inh
ibits viral DNA polymerases relative to host cell polymerases. Cross-r
esistance to cidofovir is not usually seen with human cytomegalovirus
isolates that are foscarnet-resistant, or isolates that are ganciclovi
r-resistant due to a deficiency in ganciclovir phosphorylation. Cross-
resistance is seen, however, with isolates that are ganciclovir resist
ant due to polymerase mutations. A prolonged elimination phase seen in
vivo, correlates with a long intracellular half-life seen in vitro an
d allows for efficacy in animal models of virus infection with infrequ
ent dosing or prophylaxis. Clinical studies of intravenous cidofovir i
n cytomegalovirus retinitis in patients with AIDS are claimed to show
delay of retinitis progression with maintenance doses given once every
2 weeks.