A Phase I Safety and Pharmacokinetics Study of 2',3'-Dideoxyinosine (ddI) Administered Twice Daily to Infants and Children With AIDS or Symptomatic HIV Infection

Concurrent Medication:

Allowed:

• Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis if this drug is extended to children.
• Acute therapy not exceeding 7 days with oral or intravenous acyclovir for herpes simplex infections.
• Trimethoprim / sulfamethoxazole for Pneumocystis carinii infections during course of study at discretion of investigator after discussion with the sponsor.
• Symptomatic therapy with analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy as deemed necessary by the principal investigator.

Patients must have:

• Diagnosis of AIDS as defined by CDC or meeting CDC P2 classification.
• Patients must be free of opportunistic infection or other serious bacterial, fungal, or parasitic infection at time of entry into study.
• Life expectancy > 6 months.
• Parent or guardian (and patient as applicable) able to give informed consent.
• Available for follow-up for at least 6 months.
• Allowed: Hemophilia.

Exclusion Criteria

Co-existing Condition:

Children with the following are excluded:

• Chronic hematologic disorders unrelated to coagulation defects, hemoglobinopathies, or ITP.
• Intractable diarrhea.
• No venous access.
• History of seizures within previous 2 years or currently requiring anticonvulsants for control.
• Currently active heart disease as evidenced by a cardiac arrhythmia or other significant abnormality on routine electrocardiography (ECG) or shortening fraction of \< 10 percent on echocardiogram.
• Renal disease.
• Any other clinical condition that in the opinion of the investigator makes the patient unsuitable for study.

Concurrent Medication:

Excluded:

• Antiretroviral drugs.
• Zidovudine (AZT).
• AL 721.
• Interferon.
• Corticosteroids.
• Immunomodulating drugs.
• Other systemic investigation agent.
• Ribavirin.
• Rifampin, barbiturates, or any other potent inducer or inhibitor of drug-metabolizing enzymes.
• Cytotoxic anticancer therapy.
• H-2 blockers.
• Intravenous ketoconazole.
• Immunoglobulin preparations.

Children with the following are excluded:

• Chronic hematologic disorders unrelated to coagulation defects, hemoglobinopathies, or ITP.
• Intractable diarrhea.
• No venous access.
• History of seizures within previous 2 years or currently requiring anticonvulsants for control.
• Currently active heart disease as evidenced by a cardiac arrhythmia or other significant abnormality on routine electrocardiography (ECG) or shortening fraction of \< 10 percent on echocardiogram.
• Renal disease.
• Any other clinical condition that in the opinion of the investigator makes the patient unsuitable for study.
• Renal disease.

Prior Medication:

Excluded:

• Any prior therapy which in the opinion of the investigator would make the patient unsuitable for study.

Excluded within 2 weeks of study entry:

• Trimethoprim / sulfamethoxazole.

Excluded within 1 month of study entry:

• Study drug or other antiretroviral drug or systemic investigational agent.
• Any agent known as a potent inducer or inhibitor of drug metabolizing enzymes.
• H-2 blockers.
• Ketoconazole.
• Immunoglobulin preparations.

Excluded within 3 months of study entry:

• Ribavirin.

Excluded:

• Zidovudine (AZT) for > 6 months.
• Cytotoxic anticancer therapy.

Prior Treatment:

Excluded within 4 weeks of study entry:

• Blood transfusion.
• Lymphocyte transfusions for immune reconstitution.
• Bone marrow transplant.