ANTI-HCMV ACTIVITY OF CIDOFOVIR IN COMBINATION WITH ANTIVIRAL COMPOUNDS AND IMMUNOSUPPRESSIVE AGENTS - IN-VITRO ANALYSES

1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl] cytosine, HPMPC] is an ac yclic cytosine nucleotide analogue with potent in-vitro and in-vivo ac tivity against a broad spectrum of herpesviruses including human cytom egalovirus (HCMV). Cidofovir has recently been shown to delay the prog ression 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 cidofovir were investigated in vitro. Cidof ovir in combination with GCV demonstrated synergistic inhibition of HC MV replication. Very little significant antiviral synergy or antagonis m was measured for any of the other combinations. Furthermore, none of the combinations showed increased cytotoxicity in comparison with eac h drug alone. Additionally, the antiviral activity of cidofovir was de termined in the presence of several immunosuppressive agents (hydrocor tisone, cyclosporine A, methotrexate and mycophenolic acid) that are c ommonly used in the management of organ transplantation rejection in t ransplant patients. None of these agents altered the antiviral activit y of cidofovir in vitro.