A Clinical Trial of Alternating and Intermittent Regimens of 2',3'-Dideoxycytidine and 3'-Azido-3'-Deoxythymidine in the Treatment of Patients With AIDS and Advanced ARC

Inclusion Criteria

Concurrent Medication:

Encouraged though not required:

• Inhaled pentamidine as prophylaxis for Pneumocystis carinii pneumonia (PCP).
• Allowed:
• AL-721 use is discouraged but not prohibited.
• Use of aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents should be minimized, with continuous use for > 72 hours discouraged.
• Acute therapy (7 days) with oral acyclovir.
• Acute therapy with ketoconazole.

Concurrent Treatment:

Allowed:

• Up to 4 units of packed red blood cells for hemoglobin toxicity.

All patients must have the following:

• A consistently positive serum HIV p24 antigen = or > 70 pg/ml, defined by the Abbott HIV antigen test, on two occasions. The tests must be within 1 month of study entry, separated by at least 72 hours, and the last must be within 2 weeks of starting therapy. Any negative antigen test during the period will exclude the patient from the study.
• A positive antibody to HIV confirmed by any federally licensed ELISA test kit.
• Patients in group A must have AIDS related complex (ARC) as defined by the documented presence of at least one of the following:
• Recurrent oral candidiasis.
• Hairy leukoplakia.
• History of herpes zoster.
• Temperature > 38.5 degrees C with or without night sweats, persisting for > 14 consecutive days or > 15 days in a 30-day interval prior to study entry.
• Weight loss of > 15 lbs. or 10 percent of body weight noted in a 120-day period prior to study entry.
• Diarrhea defined as = or > 3 liquid stools per day, persisting for > 30 days prior to study entry without definable cause.
• Patients in group B must have CDC-defined AIDS not requiring systemic maintenance chemotherapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Transfusion dependence requiring 2 units of blood more than once per month.
• Significant malabsorption (> 10 percent weight loss within the past 3 months with serum carotene < 75 IU/ml or vitamin A < 74 IU/ml).
• Significant cardiac or liver disease.
• Significant neurologic abnormalities defined by any one of the following:
• A significant abnormality on the ddC Neuropathy Targeted Symptom Questionnaire defined as a symptom score > 4 (moderate severity) in any one of six categories or a score > 2 (mild severity) in any two of six categories.
• Moderate abnormalities on standardized neurologic exam.
• Any severe abnormality (a value = or > 4.0) on standardized 4-arm quantitative sensory testing of vibration threshold.
• Diabetes, renal failure, or alcoholism.
• Dose-limiting or transfusion-requiring toxicity during a previous course of zidovudine therapy.
• History of idiopathic thrombocytopenic purpura.
• Requirement for prolonged acyclovir therapy. Patients in group A must not have the following:
• Opportunistic infection or malignancy fulfilling the CDC definition of AIDS.
• Neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix. Patients in group B must not have the following:
• Active opportunistic infection or AIDS-defining opportunistic infection requiring ongoing systemic therapy and/or prophylaxis other than inhaled pentamidine for Pneumocystis carinii pneumonia prophylaxis.
• Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to study entry.
• Concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix.

Concurrent Medication:

Excluded:

• Neurotoxic drugs.
• Prolonged acyclovir therapy.
• Antineoplastic therapy.
• Systemic therapy and/or prophylaxis for an AIDS-defining opportunistic infection, other than inhaled pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.
• Other antiretroviral agents, immunomodulators, or systemic corticosteroids.
• Other experimental medication.

Concurrent Treatment:

Excluded:

• Transfusion dependency (requiring 2 units of blood more than once per month).

Prior Medication:

Excluded:

• Antiretroviral agents within 60 days of study entry.
• Biologic modifiers or corticosteroids within 30 days prior to study entry.
• Dideoxycytidine (ddC).

Prior Treatment:

Excluded:

• Blood transfusion within 2 weeks of entry.

Any negative HIV p24 antigen test during the month prior to entry will exclude the patient from the study.

Active drug or alcohol abuse.

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