Los Angeles,
California
90033
Purpose:
To determine whether the rate of HIV transmission from mother to infant can be reduced by
continuous oral zidovudine (AZT) treatment to HIV infected pregnant women, intravenous AZT
during childbirth, and oral AZT treatment of the newborn infant from birth to six weeks of
age. The study is also designed to evaluate the safety of AZT for both the pregnant woman
and the newborn infant.
No method exists to prevent transmission of HIV from an infected mother to her newborn
infant. Giving an antiviral agent (such as AZT) to the mother and to the newborn could in
theory decrease the risk of infection to the newborn by reducing the exposure of the fetus
to maternal virus, or by preventive treatment of the fetus before exposure.
Study summary:
No method exists to prevent transmission of HIV from an infected mother to her newborn
infant. Giving an antiviral agent (such as AZT) to the mother and to the newborn could in
theory decrease the risk of infection to the newborn by reducing the exposure of the fetus
to maternal virus, or by preventive treatment of the fetus before exposure.
Patients are enrolled during their pregnancy, between 14 and 34 weeks of gestation. They are
chosen by random selection to receive AZT or placebo. Treatment continues until labor at
which time they begin to receive continuous intravenous study drug. Study drug treatment is
discontinued after the umbilical cord is clamped. AZT is then offered all women as per
labeled indications for 6 weeks postpartum, while appropriate medical followup is being
arranged. Mothers who develop an AIDS defining illness or whose CD4+ cell counts decrease to
less than 200 cells/mm3 during pregnancy are offered open-label drug at that time. The
mother is followed by her primary obstetrician at an AIDS Clinical Trials Unit (ACTU) or
subunit facility. The mother may deliver at the ACTU or a non-ACTU site. Treatment of the
infant is started in the newborn nursery and continues on an outpatient basis. Infants
receive the same study treatment as the mother for 6 weeks, and are monitored to week 78.
Criteria:
Inclusion Criteria
Concurrent Medication:
Allowed for infants:
- Treatment for signs of drug withdrawal (e.g., phenobarbital, chlorpromazine, tincture
of opium, paregoric, or Valium).
- Treatment for nonserious conditions (e.g., syphilis treatment, hepatitis B vaccine).
- All essential supportive treatment for conditions that are nonlife threatening as
deemed by the on-site pediatrician.
- Acetaminophen.
- Standard immunizations.
- Allowed for women:
- All medications/treatments as required for normal OB care of HIV+ women, except as
noted under exclusions.
- Pneumocystis prophylaxis as indicated.
- Topical steroids. Parenteral and oral steroids for 6 or fewer days.
Concurrent Treatment:
Allowed for pregnant woman:
Blood transfusion for anemia (hemoglobin less than 7 g/dl).
Allowed for infant:
- Blood transfusions for anemia except if attributed to study drug.
-
Patients must:
- Have HIV infection.
- Intend to carry pregnancy to term.
- Be willing to be followed by a participating ACTG center for duration of the study.
- Be able to provide informed consent (if available, father of the fetus must also
provide informed consent).
- Infants may enroll simultaneously in other pediatric protocols after completing the
initial 6 weeks of study treatment.
- Inclusion age for women is 13 years old or more or IRB local age of consent.
- Inclusion age for infants is 0 to 20 months.
Exclusion Criteria
Co-existing Condition:
Infants with the following conditions or symptoms are excluded:
- Requiring treatment for hyperbilirubinemia (except phototherapy).
Concurrent Medication:
Excluded:
- Infants:
- Antiretroviral drugs or vaccines.
- Excluded during current pregnancy:
- Zidovudine (AZT).
- Other antiretroviral agents (e.g., rCD4, CD4-IgG, d4T, didanosine (ddI),
dideoxycytidine (ddC)), passive immunotherapy (e.g., HIVIG), anti-HIV vaccines,
cytolytic chemotherapeutic agents.
- Corticosteroids for equal to or more than 7 days.
Patients with the following are excluded:
- Evidence of preexisting fetal anomalies that may (1) result in a high probability
that the fetus/infant will not survive to the end of the study period (e.g.,
anencephaly, renal agenesis, or Potter's syndrome); or (2) increase the fetal tissue
concentration of zidovudine (AZT) or its metabolites to a toxic level (e.g., neural
tube or ventral wall defects).
- Baseline sonogram completed within 28 days prior to randomization that demonstrates
2nd trimester findings of anencephaly or oligohydramnios, or 3rd trimester findings
of unexplained polyhydramnios, fetal hydrops, ascites or other evidence of
preexisting in-utero anemia.
- History of intolerance to AZT dose of 500 or less mg/day prior to this pregnancy that
resulted in discontinuation of treatment for more than 4 weeks.
- Recipient of AZT during current pregnancy for any indication or meet criteria for AZT
as defined by this protocol (CD4+ cell counts less than 200 cells/mm3 or AIDS).
- Infants not having parent/guardian available to give informed consent if necessary.
Prior Treatment:
Excluded during current pregnancy:
- Radiation therapy.