Is combination antiviral therapy for CMV superior to monotherapy?

Many clinicians are under the impression that the combination of ganciclovir (GCV) and foscarnet is synergistic versus cytomegalovirus (CMV) and/or that combination therapy might prevent the emergence of resistance to one or both antivirals. The combination is frequently used when resistance to either drug is suspected.

To review in vitro and clinical data regarding the activity of ganciclovir plus foscarnet and evidence of synergy between the two drugs.

We reviewed two in vitro studies of synergy between ganciclovir and foscarnet followed by reviewing all clinical studies utilizing series of patients.

The combination of ganciclovir and foscarnet was synergistic against three clinical isolates, the Towne strain and one laboratory derived strain moderately resistant to GCV but synergy was not demonstrated against laboratory derived strains highly resistant to GCV or foscarnet. AD169, susceptible to both drugs, was not inhibited synergistically by the combination in one study but was in the second study. In the only carefully controlled in vivo study of combination versus monotherapy for GCV susceptible viremia superiority of the combination was not demonstrated. In treating clinically resistant CMV retinitis, the combination was superior to continued or alternative monotherapy.

There is suggestive but inconclusive evidence of in vitro synergy for the combination of GCV and foscarnet versus CMV with very limited data versus GCV resistant virus. The in vivo data for synergy is even less convincing. Additional in vitro and in vivo data is needed, especially to prevent or treat CMV resistance.