A Phase III Study to Evaluate the Safety, Tolerance, and Efficacy of Early Treatment With Zidovudine (AZT) in Asymptomatic Infants With HIV Infection

AZT is currently indicated for primary treatment in children with HIV-associated signs and symptoms and for those with significant immunodeficiency. This study will attempt to determine whether early treatment with AZT prevents the development of symptoms in HIV-infected infants who are asymptomatic.

Patients are randomized to receive oral AZT (at age-adjusted doses) or placebo. Patients are evaluated at weeks 2 and 4 and every 4 weeks thereafter; those who reach a study endpoint will have their treatment unblinded to allow the clinician to determine which treatment regimen the patient should then receive. Patients who meet the criteria for changes to open-label AZT will be given the appropriate age-adjusted dose without unblinding the original randomization assignment. Patients who complete or discontinue treatment are followed every 6 months for up to 2 years.

Inclusion criteria

Patients must have:

• HIV infection.
• CD4 count >= 2000 cells/mm3 AND >= 30 percent of total lymphocytes.
• No signs or symptoms of HIV infection (other than lymphadenopathy, mild hepatomegaly, hypergammaglobulinemia, or splenomegaly, which is permitted).
• Consent of parent or guardian.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Serious acute infection requiring parenteral therapy at time of entry.
• One or more serious, proven bacterial infections including any of the following:
• septicemia; pneumonia; meningitis; bone or joint infection; or abscess of an internal organ or body cavity (excluding otitis media or superficial skin or mucosal abscesses) that are caused by Haemophilus, Streptococcus (including pneumococcus), or other pyogenic bacteria.
• Clinical neurologic/neuropsychologic deficits, or a head circumference less than the fifth percentile.

Concurrent Medication:

Excluded:

• Any agent with known antiretroviral activity.
• Acetaminophen, ibuprofen, or aspirin for more than 72 hours continuously.

Prior Medication:

Excluded:

• More than 7 weeks of prior antiretroviral or immunomodulator therapy post-natally.

Recommended:

• PCP prophylaxis.
• Immunizations according to current recommendations.