A Study of Zidovudine in HIV-Infected Pregnant Women and Their Children
Condition: HIV Infections; Pregnancy
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      AMENDED: To evaluate the pharmacokinetics of intravenously administered AZT to HIV-1 infected
      pregnant women in labor; to evaluate the pharmacokinetics and urinary excretion of AZT and
      its metabolites in newborns of HIV-1 infected mothers who receive IV AZT only during labor;
      to evaluate the safety of IV AZT administered by continuous infusion to HIV-1 infected
      laboring women and their infants. Original design: To determine the distribution and
      elimination of zidovudine (AZT) in the body as well as its safety in the treatment of
      pregnant women and their unborn children. The information derived from this study is required
      in order to design a future study that will assess the efficacy of AZT in reducing the
      transmission rate of HIV-1 from seropositive women to their fetus by treating them during the
      third trimester of pregnancy.

      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.
    

Detailed description: 
      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.
    

Intervention name(s): Zidovudine
Intervention type(s): Drug
Intervention MeSH terms: Zidovudine
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pregnancy; Pregnancy Complications, Infectious; Prenatal Exposure Delayed Effects; Drug Evaluation; Acquired Immunodeficiency Syndrome; Zidovudine