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

Primary: To determine the efficacy of early treatment with zidovudine (AZT) in HIV-infected asymptomatic infants. To determine the safety and tolerance of AZT in this patient population.

Secondary: To compare the virologic and immunologic parameters between the treatment groups. To determine the efficacy of AZT as an early treatment to prevent development of CD4+ cell depletion in HIV-infected asymptomatic infants.

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.

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.