A Phase I Trial To Evaluate Zidovudine (ZDV) in HIV-1 Infected Pregnant Women and Their Offspring

An estimated 30 percent to 40 percent infected pregnant women risk transmission of HIV-1 to their infants, whether they be symptomatic or asymptomatic. Zidovudine (AZT) has previously demonstrated its effectiveness as a potent inhibitor of HIV replication in vitro and in adult patients; benefits of treatment include decreased mortality rate, decreased incidence of opportunistic infections, and increased number of CD4 cells. Phase I AZT studies in children, however, have resulted in uncontrolled information regarding clinical efficacy. The present study, therefore, will investigate the safety and pharmacokinetics of intravenous (IV) and oral AZT administration to HIV-1 infected pregnant women in the 3rd trimester, as well as the safety and efficacy of such treatment in their newborns.

It is hoped that the results will be instrumental in designing future studies to assess the efficacy of AZT in reducing the transmission risk of HIV-1.

AMENDED: For the pharmacokinetic and safety study of AZT during labor and in the newborn infants, women who were screened and have consented are included in this part of the study. 6 mother-infant pairs without a history of intravenous drug abuse and 4 pairs with such a history are evaluated. The mother receives an infusion of AZT over 1 hour followed by continuous infusion of AZT for at least 4 hours until delivery. Pharmacokinetic data is collected on all patients including those who deliver before receiving 4 hours of AZT infusion.

AMENDED: The trial will proceed as described above except that the first 2 methadone patients enrolled will receive half the AZT dose given to the non-methadone patients. Results will be evaluated before dosing of additional methadone-use patients is done. Original design: Following evaluation, patients receive one intravenous dose of AZT over a 1-hour period. One day later, patients begin taking AZT capsules 5 times a day by mouth for the remaining weeks prior to labor.

During labor, patients continue to receive AZT intravenously every 4 hours until they deliver their babies. Blood and urine tests are made to measure the amounts of AZT in the mother's and, after delivery, the baby's body fluids. AZT is stopped after the baby has been delivered. The initial enrollment is six women with no history of intravenous drug abuse plus another four women with a history of intravenous drug use, who have been receiving methadone maintenance therapy. These women are not required to have a negative urine toxicology screen for illicit drugs to enter the study.