Suppression of maternal virus load with zidovudine, didanosine, and indinavir combination therapy prevents mother-to-fetus HIV transmission in macaques

Recently, we developed a maternal-fetal macaque model using a highly pathog enic HIV-2 strain, HIV-2(287), to study the time course of HIV transmission in utero. Most pregnant macaques (Macaca nemestrina) infected with HIV-2(2 87) (10-10(3) infective doses) transmitted HIV to their fetuses. as verifie d by positive identification of virus-infected mononuclear cells and free v iral RNA in fetal blood. To determine whether an antiretroviral drug combin ation therapy composed of two dideoxynucleosides, azidothymidine (15 mg/kg) and dideoxyinosine (15 mg/kg), and a protease inhibitor, indinavir (25 mg/ kg), could completely inhibit mother-to-fetus HIV transmission, we administ ered these drugs orally through gastric catheters to five pregnant macaques infected with 10 infective doses of HIV-2(287). Beginning 30 minutes after HIV inoculation, the dams were given the combination antiviral therapy thr ee times daily until delivery by cesarean section. Drug treatment reduced t he maternal virus load to a minimally detectable level but did not prevent primary HIV-2(287) infection. All fetal and infant blood samples were virus negative by internally controlled RNA polymerase chain reaction (QC-RNA-PC R) and virus coculture assays. Fetal and infant CD4(+) T-cell levels remain ed normal throughout the experiment. These findings strongly suggest that c ombination chemotherapy with azidothymidine, dideoxyinosine, and indinavir can suppress maternal viral load enough to prevent mother-to-fetus transmis sion of HIV.