The Safety of Different Dose Levels of Zidovudine in HIV-Infected Children

Inclusion Criteria

Concurrent Medication:

AMENDED:

• 03-19-91 Prophylaxis for PCP is recommended according to current practice guidelines. As per published recommendations, primary prophylaxis with TMP / SMX on a M-T-W basis is encouraged.

Allowed:

• Immunoglobulin therapy as single dose exposure prophylaxis or for children with hypogammaglobulinemia.
• Trimethoprim / sulfamethoxazole (TMP / SMX) and parenteral or aerosolized pentamidine for prophylaxis for Pneumocystis carinii pneumonia for children with AIDS and/or CD4+ counts = or < 500 cells/mm3.
• Systemic ketoconazole and acyclovir, or oral nystatin for acute therapy.
• Aerosol ribavirin for short-term treatment of acute respiratory syncytial virus (RSV).

AMENDED:

• 9/17/90 enrollment is limited to children < 6 years of age.
• Original design:
• Patients must have the following:
• Parent or guardian available to give written informed consent.
• Laboratory evidence of HIV infection.
• Children < 15 months of age, with CD4+ cell count > 500 cells/mm3, who are thought to have acquired HIV through perinatal transmission and whose only laboratory evidence of HIV infection is a positive antibody test, must also have one or more of the laboratory criteria described in Disease Status AND one or more of the disease criteria that are required of children > 15 months old with CD4+ cell counts > 500 cells/mm3.

Prior Medication:

Allowed:

• Aerosol ribavirin.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

Previous AIDS-defining opportunistic infection or neoplasms as specified by the CDC surveillance criteria for AIDS.

• Previous unexplained recurrent, serious bacterial infections (two or more within a 2-year period) including sepsis, meningitis, pneumonia, abscess of an internal organ, and bone/joint infections caused by Haemophilus, Streptococcus, or other pyogenic bacteria.
• Qualifying for entrance criteria to zidovudine (AZT) + or - gammaglobulin (ACTG 051).
• Encephalopathy.
• Failure to thrive (defined as a child who crosses two percentile lines on the growth chart or child who is < fifth percentile and does not follow curve) and/or oral candidiasis for at least 2 months despite appropriate topical therapy.
• Lymphocytic interstitial pneumonitis (LIP) with steroid dependency or requiring supplemental oxygen.
• Preexisting malignancies.

Concurrent Medication:

AMENDED:

• 03-19-91 Prophylaxis with antiviral or antifungals agents, except for PCP prophylaxis is prohibited.
• Drugs that are metabolized by hepatic glucuronidation should be used with caution.

Excluded:

• Prophylaxis for oral candidiasis or otitis media or other infections (sinusitis, urinary tract infections).
• Immunoglobulin therapy not specifically allowed.
• Ketoconazole, acyclovir, or nystatin for prophylaxis.
• Drugs that are metabolized by hepatic glucuronidation and might alter metabolism of zidovudine (AZT).

Patients with the following are excluded:

• Previous AIDS-defining opportunistic infection or neoplasms as specified by the CDC surveillance criteria for AIDS.
• Previous unexplained recurrent, serious bacterial infections (two or more within a 2-year period) including sepsis, meningitis, pneumonia, abscess of an internal organ, and bone/joint infections caused by Haemophilus, Streptococcus, or other pyogenic bacteria.
• Qualifying for entrance criteria to zidovudine (AZT) + or - gammaglobulin (ACTG 051).
• Encephalopathy.
• Failure to thrive (defined as a child who crosses two percentile lines on the growth chart or child who is < fifth percentile and does not follow curve) and/or oral candidiasis for at least 2 months despite appropriate topical therapy.
• Lymphocytic interstitial pneumonitis (LIP) with steroid dependency or requiring supplemental oxygen.
• Preexisting malignancies.

Prior Medication:

Excluded within 2 weeks of study entry:

• Any other experimental therapy or drugs that cause prolonged neutropenia or significant nephrotoxicity.

Excluded within 1 month of study entry:

• Antiretroviral agents.
• Immunomodulating agents including immunoglobulin, interferon, isoprinosine, and IL-2.

Excluded within 2 months of study entry:

• Systemic ribavirin for retroviral therapy.

Prior Treatment:

Excluded within 1 month of study entry:

• Lymphocyte or red blood cell transfusions.

Active alcohol or drug abuse.