A Phase I/II Study of Hyperimmune IVIG in Slowing Progression of Disease in HIV-Infected Children

A Phase I/II Study of Hyperimmune IVIG in Slowing Progression of Disease in HIV-Infected Children

To evaluate the safety, tolerance, pharmacokinetics, and antiviral activity of human anti-HIV immune serum globulin ( HIVIG ) at three dosage levels in HIV-infected children.

Passive antibody therapy has been used with limited success in treating advanced HIV disease in adults. HIVIG is manufactured from HIV antibody-rich plasma taken from asymptomatic donors. It is hypothesized that HIVIG will decrease the viral burden of moderately advanced HIV-positive children.

Passive antibody therapy has been used with limited success in treating advanced HIV disease in adults. HIVIG is manufactured from HIV antibody-rich plasma taken from asymptomatic donors. It is hypothesized that HIVIG will decrease the viral burden of moderately advanced HIV-positive children.

Children are randomized to receive HIVIG every 4 weeks for 6 months at one of three dose levels, then are followed for 3 months after the final infusion.

Inclusion Criteria

Concurrent Medication:

Required:

• PCP prophylaxis according to CDC guidelines.

Allowed:

• Varicella-zoster immunoglobulin.
• Hepatitis B immunoglobulin.
• Prophylactic therapies not involving immunoglobulin.

Patients must have:

• HIV infection.
• CD4 count > 200 cells/mm3 (ages 2-5 years) or > 100 cells/mm3 (age > 5 years).
• Antiretroviral therapy for at least 6 months, with no change in regimen for at least 3 months prior to study entry.
• Plasma ICD p24 >= 70 pg/ml that is stable or increasing prior to study entry.
• Life expectancy of at least 6 months.

Prior Medication: Required:

• Antiretroviral therapy for at least 6 months, with stable dose for at least 3 months.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Severe diarrhea, nephrotic syndrome, or other protein-losing state that requires large doses of IVIG.
• Any other condition requiring dosing with IVIG (e.g., ITP, hypogammaglobulinemia).
• Acute illness with temperature >= 100 F and/or with IV antibiotics.
• Grade 3 or worse clinical toxicities.
• Unable to tolerate IV infusions at a minimum rate of 0.02 ml/kg/min.
• Concomitant participation in an experimental antiretroviral or HIV vaccine trial.

Concurrent Medication:

Excluded:

• IVIG.
• Chemotherapy for an active malignancy.
• MMR or rubella vaccinations.
• Intramuscular immunoglobulin.

Patients with the following prior condition are excluded:

• History of severe reaction to IVIG.

Prior Medication:

Excluded:

• IVIG within the past 60 days.
• Chemotherapy for an active malignancy within the past year.
• MMR or rubella vaccinations within the past 6 months.
• Intramuscular immunoglobulin within the past 60 days.

Ongoing drug or alcohol abuse.