Inhibition of human cytomegalovirus by combined acyclovir and vidarabine.
The inhibition of human cytomegalovirus (HCMV) isolates by acyclovir (ACV) and vidarabine (ara-A) was assessed by using an infectious-center plaque-reduction assay. When fixed concentrations of 4.5 micrograms of ACV and 250 ng of ara-A per ml were compared singly and in combination, the viral inhibition resulting from the ACV-ara-A combination was synergistic for three of four HCMV clinical isolates studied and additive for one HCMV isolate. An additional four HCMV strains obtained at postmortem examination from the lungs of bone marrow transplant patients were assessed for sensitivity to ACV-ara-A by using the dose required for 50% viral inhibition (ID50) as the endpoint. The mean ID50 of ACV for the four HCMV isolates was 12.3 micrograms/ml, whereas the mean ID50 of ara-A was 3.4 micrograms/ml. When 1 microgram of ara-A per ml (which yielded a mean plaque reduction of 23.6%) was combined with ACV, a mean of 5.2 micrograms of ACV per ml was required for 50% viral inhibition. The sum of the fractional inhibitory concentrations for each of the four HCMV isolates was less than 1, indicating synergy by the ACV-ara-A combination. Although DNA synthesis in growing human embryonic lung fibroblast (HEL) cells, as determined by [3H]thymidine incorporation, was diminished to 61% of that in untreated control cells when 22.5 micrograms of ACV and 1 microgram of ara-A per ml were used, there was no additive inhibition of DNA synthesis when the two-drug combination was used. HEL cell growth remained at 97% of control cell growth at 72 h when concentrations as high as 45 micrograms of ACV combined with 1 microgram of ara-A per ml were used.
Spector
S A
SA
Kelley
E
E
D000212:Acyclovir / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003587:Cytomegalovirus / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis; D006801:Humans; D014740:Vidarabine / Q000494:pharmacology*; D010948:Viral Plaque Assay
D004279:DNA, Viral; D014740:Vidarabine; D000212:Acyclovir