A Randomized, Double Blind, Comparative Study of Dideoxycytidine (ddC) Alone or ddC/AZT Combination Versus Zidovudine (ZDV) Alone in Patients With HIV Infection Who Have Received Prior ZDV Therapy

Inclusion Criteria

Concurrent Medication:

Required:

• Zidovudine (AZT) = or > 300 mg/day for 6 weeks prior to study entry.

Allowed:

• Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), candidiasis, and herpes.
• 21 day course of adjuvant systemic corticosteroids for moderate to severe PCP.
• Maintenance treatment with pyrimethamine, sulfadiazine, amphotericin, fluconazole, ketoconazole, acyclovir, ganciclovir, or medications for tuberculosis or Mycobacterium avium for patients who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes virus infections, cytomegalovirus infections, tuberculosis or Mycobacterium avium intracellulare.
• 14 day course of metronidazole.
• Erythropoietin and megace if clinically indicated.
• Isoniazid if patient has no peripheral neuropathy at entry and is taking pyridoxine = or > 50 mg/day concomitantly.
• Phenytoin if patient has < grade 2 peripheral neuropathy at entry and has been stable on phenytoin = or > 3 months.

Patients must have:

• Ability and willingness to give informed consent.
• Written informed consent from a parent or guardian if < 18 years old.
• Been tolerating zidovudine (AZT) therapy.
• Diagnosis of HIV infection.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Kaposi's sarcoma or other malignancy requiring therapy.
• Active opportunistic infections.
• Peripheral neuropathy as manifested by complaints of moderate pain, burning, numbness, or tingling in hands/arms or feet/legs; moderate sensory deficit in the upper or lower extremities; or motor weakness in the upper or lower extremities.

Concurrent Medication:

Excluded:

• Other experimental medications.
• Other anti-HIV drugs.
• Biologic response modifiers.
• Cytotoxic chemotherapy.
• Drugs that could cause peripheral neuropathy including phenytoin not specifically allowed, hydralazine, nitrofurantoin, vincristine, cisplatinum, dapsone, disulfiram, and diethyldithiocarbamate.

Concurrent Treatment:

Excluded:

• Radiation therapy.

Patients with the following are excluded:

• Active opportunistic infection. Must have ended acute therapy at least 14 days prior to study entry.
• Peripheral neuropathy = or > grade 2.
• History of intolerance to 500 to 600 mg/day of zidovudine (AZT) as manifested by the same recurrent grade 3 toxicity requiring dose interruptions and dose reductions to < 500 mg/day or any prior grade 4 toxicity.
• Prior development of peripheral neuropathy on ddI = or > grade 2.

Prior Medication:

Excluded:

• Dideoxycytidine (ddC).

Required:

• Zidovudine (AZT) for total of at least 24 weeks; and included within that time period, AZT = or > 300 mg/day for 6 weeks prior to the study entry.

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