A Phase I Study of Safety and Pharmacokinetics of Nevirapine in HIV-1 Infected Pregnant Women and Neonates Born to HIV-1 Infected Mothers

Treatment of HIV-1 infected pregnant women during active labor may result in therapeutic levels of nevirapine in the neonate at the time of exposure to HIV-1 during parturition, decreasing the neonate's risk of infection.

Pregnant women in active labor receive single doses of oral nevirapine. The neonates of the first 4-6 (PER AMENDMENT 8/27/96, was 4) mothers receive no drug, while the neonates of the second 4-6 (PER AMENDMENT 8/27/96, was 4) patient cohort receive a single dose of nevirapine. If neonatal antiviral levels of nevirapine are not sustained for 7 days after the single dose, a third cohort of 4-6 (PER AMENDMENT 8/27/96, was 4) pregnant women will receive a single dose of nevirapine and their neonates will receive multiple doses of nevirapine to maintain an antiviral effect for 7 days.

Inclusion criteria

Concurrent Medication:

Allowed:

• AZT (mothers and neonates).
• Oral asthma inhalers (mothers).

Concurrent Treatment:

Allowed:

• Phototherapy (neonates).

MOTHERS must have:

• HIV infection.
• Estimated gestational age >= 34 weeks.
• No active opportunistic infection at study entry.

PER AMENDMENT 8/27/96:

• A pre-enrollment plasma HIV-1 RNA level greater than 10,000 copies/ml.

Exclusion criteria

Co-existing Condition:

MOTHERS with the following symptoms or conditions are excluded:

• Intrauterine growth retardation.
• Fetal anomaly incompatible with life as determined by pre-entry ultrasound.
• Participation during current pregnancy in any other therapeutic or vaccine perinatal trial.
• Known hypersensitivity to any benzodiazepine.
• Serious bacterial infection.

Concurrent Medication:

Excluded:

• Any antiretroviral other than AZT.
• Corticosteroids (other than oral asthma inhalers).
• Anticoagulants.
• Any clavulanic acid-containing formulation (e.g., Augmentin, Timentin).
• Benzodiazepines other than study drug.
• Phenobarbital.
• Barbiturates.
• Antacids.
• Magnesium sulfate.

Prior Medication:

Excluded:

• Prior nevirapine.

Current use of illicit substances and/or active chronic alcohol use.