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

Inclusion Criteria

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.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety