A Multicenter Phase I Trial To Evaluate the Safety and Pharmacokinetics of Intravenous and Oral Zidovudine in Infants With Perinatal Human Immunodeficiency Virus (HIV) Exposure

Inclusion Criteria

Infant gestation period must have been = or > 36 weeks and birthweight must = or > 2000 grams. Active infection must not be present at the time of entry into the study although an HIV culture or P24 serum antigen determination must be obtained prior to study entry. The child must have a life expectancy greater than 3 months. Parents or guardian must be available to give informed consent.

Prior Medication:

Allowed on a case-by-case basis:

• Some essential supportive therapies including antibiotics.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Any of the following laboratory findings within 2 weeks of study entry.
• A total bilirubin > 2 times age-adjusted upper limit of normal.
• Liver transaminase values > 3 x upper limit of normal.
• Serum creatinine > 1.5 x upper limit of normal.
• Total granulocyte count < 1500 cells/mm3.
• Hemoglobin < 10 g/dl or hemoglobinopathy.
• A urine toxicology screen positive for any drug or chemical.
• Infants must not have hemoglobinopathy or active infection at entry.

Prior Medication:

Excluded within 2 months of study entry:

• Antiretroviral agents.
• Excluded within 4 weeks of study entry:
• Immunomodulating agents including steroids, interferon, isoprinosine, and interleukin.
• Immunoglobulin.
• Excluded within 2 weeks of study entry:
• Any other experimental therapy, drugs which cause prolonged neutropenia or significant nephrotoxicity, or rifampin / rifampin derivatives.
• Some essential supportive therapies including antibiotics may have infrequent or transient effects. These drugs will be considered on a case-by-case basis.

Prior Treatment:

Excluded within 2 weeks of study entry:

• Red blood cells or whole blood transfusion.
• Excluded within 4 weeks of study entry:
• Lymphocyte transfusions for immune reconstitution.

Infants may not be entered into the study during the first 2 weeks of life if their mother received methadone therapy during the last trimester of her pregnancy or used any known illicit drug. A maternal urine toxicology screen may be optionally performed prior to entry of the child, and children whose mothers have a screen which is positive for any drugs or chemicals may not be enrolled within 2 weeks of the positive screen.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety