Effect of Maternal Treatment with Cyclic HPMPC

Background. Cytomegalovirus (CMV) infection of the fetus is the leading cause of congenital infection. Using the guinea pig model of congenital CMV infection, we sought to determine whether antiviral treatment of a CMVinfected dam could improve the outcome of offspring. Methods. Pregnant Hartley guinea pigs were inoculated with guinea pig CMV (GPCMV) during the late second/early third trimester of gestation. Guinea pigs received either 1 dose of cyclic 1-[((s)-2-hydroxy-2-oxo1,4,2,-dioxaphosphorinan-5-yl)methyl]cytosine dihydrate (cHPMPC; 35 mg/kg) or placebo 24 h after GPCMV infection. Guinea pigs were monitored until delivery or were killed 10 days after infection, for the evaluation of the effect of cHPMPC on viral replication by polymerase chain reaction analysis in various dam and pup tissues. Results. cHPMPC treatment of infected dams improved pup survival from 28.2% (11/39) to 83.7% (36/43) (P< .00l) and extended the duration of pregnancy. cHPMPC treatment did not prevent infection of the placenta or disseminated infection of the dam and pup but significantly decreased the amount of GPCMV in tissues. GPCMV DNA levels in the placenta were reduced from 3.54 to 2.12 loglo genome copiesiJ-tg of DNA (P< .0001). Conclusions. Treatment of the GPCMV-infected pregnant dam with 1 dose of cHPMPC improves the outcome of congenital infection and decreases viral replication in a guinea pig model.