Anti-HCMV Activity of Cidofovir in Combination with Antiviral Compounds and Immunosuppressive Agents: In-Vitro Analyses

Abstract

SummaryCidofovir 1-[(S)-3-hydroxy-2-(phosphonomethoxy) propyl] cytosine, HPMPC] is an acyclic cytosine nucleotide analogue with potent in-vitro and in-vivo activity against a broad spectrum of herpesviruses including human cytomegalovirus (HCMV). Cidofovir has recently been shown to delay the progression of HCMV retinitis in AIDS patients. Therefore, the effects of several antiviral compounds (GCV, AZT, ddC, ddl, d4T, 3TC and PMEA) on the anti-HCMV activity of cldofovir were investigated in vitro. Cidofovir in combination with GCV demonstrated synergistic inhibition of HCMV replication. Very little significant antiviral synergy or antagonism was measured for any of the other combinations. Furthermore, none of the combinations showed increased cytotoxicity in comparison with each drug alone. Additionally, the antiviral activity of cidofovir was determined in the presence of several immunosuppressive agents (hydrocortisone, cyclosporine A, methotrexate and mycophenolic acid) that are commonly used in the management of organ transplantation rejection in transplant patients. None of these agents altered the antiviral activity of cidofovir in vitro.

Clinical uses of cidofovir

“…Furthermore, none of the combinations showed increased cytotoxicity in comparison with each drug alone. 28 Snoeck et al have demonstrated that cidofovir in combination with ganciclovir, AZT, foscarnet, or acyclovir showed additive to synergistic inhibition of HCMV replication in vitro. 29 Additionally, antiviral activity of cidofovir was determined in the presence of several immunosuppressive agents (hydrocortisone, cyclosporine A, methotrexate and mycophenolic acid) that are commonly used in the management of organ transplantation rejection in the transplant patients.…”