A Study of Dideoxycytidine Plus Zidovudine (AZT) in HIV-Infected Children Who Have Taken AZT

A Phase II Study to Evaluate Pharmacokinetics, Safety, Tolerance and Activity of Dideoxycytidine (ddC) Administered in Combination With Zidovudine (AZT) in Stable, AZT-Treated Pediatric Patients With HIV Infection

PRIMARY: To determine safety, tolerance, and pharmacokinetics of zidovudine (AZT) and zalcitabine (dideoxycytidine; ddC) when given in combination in clinically stable AZT-treated children.

SECONDARY: To compare combination therapy with mono drug therapy for antiviral activity and laboratory markers of disease progression, as determined by virologic and immunologic determinations. To evaluate the influence of combination therapy on disease progression as determined by evaluation of clinical criteria.

In children currently being treated with AZT, it is unknown whether the addition of another antiretroviral agent such as ddC would help increase efficacy and tolerance. This study will examine the possible advantages of combination AZT/ddC therapy over monotherapy with AZT alone.

In children currently being treated with AZT, it is unknown whether the addition of another antiretroviral agent such as ddC would help increase efficacy and tolerance. This study will examine the possible advantages of combination AZT/ddC therapy over monotherapy with AZT alone.

Patients are stratified according to duration of ongoing AZT therapy and are randomized to receive AZT either alone or in combination with ddC. Patients receive therapy until the last patient enrolled completes 32 weeks of therapy. The study may be extended for two additional 32-week periods on an optional basis.

Inclusion Criteria

Concurrent Medication:

Recommended:

• PCP prophylaxis.

Allowed:

• Intravenous and/or intramuscular immunoglobulin.
• Acyclovir (no more than 30 mg/kg/day PO).
• Ketoconazole (no more than 10 mg/kg/day).
• Nystatin.
• Aspirin, acetaminophen, nonsteroidal anti-inflammatory drugs, sedatives, and barbiturates, not to exceed 72 hours.
• Isoniazid in combination with pyridoxine, provided there is no evidence of peripheral neuropathy.
• Trimethoprim / sulfamethoxazole.
• Amphotericin B (no more than 1 mg/kg for 5 days/week).
• Aerosolized ribavirin for bronchiolitis.
• Hematopoietic agents.
• Other drugs with little nephro-, hepato-, or cytotoxicity.
• Nutritional support for HIV wasting syndrome or malnutrition.

Patients must have:

• HIV infection.
• Ongoing stable AZT therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Disease progression while on AZT, to the extent that the patient meets the criteria for advanced disease protocols.
• Known allergy or sensitivity to ddC.
• Cardiomyopathy.

Concurrent Medication:

Excluded:

• Biologic modifiers other than IVIG, steroids, or hematopoietic agents.
• Investigational medications unless approved by protocol chair.
• Medications known to cause pancreatitis (unless ddC is interrupted while these medications are given).

Patients with the following prior conditions are excluded:

• History of intolerance or toxicity to AZT.
• History of symptomatic pancreatitis.
• History of peripheral neuropathy or abnormal nerve conduction velocity test.

Prior Medication:

Excluded:

• Antiretroviral agents other than AZT within 2 weeks of study entry.

Required:

• Ongoing stable AZT therapy for more than 6 weeks duration.