Effects of acyclovir combined with other antiviral agents on human cytomegalovirus

At present, there is no effective therapy for human cytomegalovirus (CMV) infections. Although acyclovir inhibits in vitro clinical isolates of CMV, preliminary human trials suggest that acyclovir may not be successful as a single antiviral agent in treating CMV infections. The antiCMV activity of acyclovir in combination with human fibroblast interferon (IFN-beta), phosphonoformic acid (PFA), or trifluorothymidine (TFT) was therefore evaluated. When acyclovir (20 microM) was combined with IFN-beta (25 U/ml), additive antiviral effects were observed for the four clinical CMV isolates studied and the laboratory adapted strain, AD-169. The combination of acyclovir (20 microM) with PFA (25 microM) was synergistic for all four clinical isolates studied, but additive for the AD-169 strain. Similarly, the combination of acyclovir (20 microM) and TFT (0.17 microM) was synergistic for three of four clinical isolates, and additive for one clinical strain and the AD-169 virus. These findings suggest that acyclovir combined with other antiviral agents may be useful in the treatment of CMV disease.