CIDOFOVIR, A NEW AGENT WITH POTENT ANTI-HERPESVIRUS ACTIVITY

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.