Antiviral Agents: Cidofovir and Brincidofovir

Cidofovir (CDV) was the first nucleotide analog approved for clinical use, for the systemic treatment of human cytomegalovirus (HCMV) retinitis in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. To overcome side effects, particularly nephrotoxicity of CDV, brincidofovir (BrinCDV) an oral prodrug of CDV has been developed. In vitro studies demonstrate that CDV and BrinCDV are active against a comprehensive range of DNA viruses, particularly important is CDV’s activity against acyclovir-resistant herpes simplex and varicella zoster viruses and human cytomegalovirus mutants with alterations in the viral UL97 gene. Despite broad in vitro activity, clinical benefit has not been demonstrated for most viruses. In-depth discussion of CDV and BrinCDV pharmacokinetics, clinical utility, and toxicities is explored.