Double-Blind Comparison of the Efficacy of Continued Zidovudine Versus 2',3'-Dideoxyinosine (ddI) (BMY-40900) for the Treatment of Patients With AIDS or AIDS-Related Complex and Increasing Symptomatology Despite Treatment With Zidovudine

Inclusion criteria

Concurrent Medication:

Allowed for Hematologic toxicity:

• Erythropoietin.
• Colony-Stimulating Factors.
• Allowed for prophylaxis of Pneumocystis carinii pneumonia (PCP):
• Aerosolized pentamidine.
• Trimethoprim/sulfamethoxazole.
• Dapsone.
• NOTE:
• If intravenous pentamidine is required for treatment of PCP, study drug should be suspended until one week after completion of intravenous pentamidine.
• Allowed:
• Prophylactic or suppressive therapy begun prior to study entry with the exception of neurotoxic agents (as defined in the protocol).

Concurrent Treatment:

Allowed:

• Transfusions for hematologic toxicity.

Exclusion criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Active acute AIDS defining infection.
• Clinical evidence of acute pancreatitis in the last two years or chronic pancreatitis.
• Dementia of such severity that patient cannot give informed consent.
• Grade 2 or worse peripheral neuropathy as defined by Targeted Neuropathy Score (Schaumberg).
• Prior Cytomegalovirus disease requiring ongoing systemic ganciclovir therapy.
• Extensive Kaposi's sarcoma or other malignancy requiring systemic cytotoxic myelosuppressive or neurotoxic chemotherapy.
• Cardiomyopathy or the need for antiarrhythmic therapy.
• Inability to tolerate at least 600 mg per day of zidovudine (AZT).
• Seizures within the last 6 months or the need for anticonvulsant therapy.

Concurrent Medication:

Excluded:

• Ganciclovir (DHPG).
• Myelosuppressive or neurotoxic chemotherapy.
• Antiarrhythmic therapy.
• Anticonvulsant therapy.
• Neurotoxic agents (as defined in the protocol).
• NOTE:
• If intravenous pentamidine is required for treatment of Pneumocystis carinii pneumonia (PCP), study drug should be suspended until 1 week after completion of intravenous pentamidine.

Patients with the following are excluded:

• Symptoms and conditions defined in the Patient Exclusion Co-Existing Conditions field.
• Average of two sequential CD4 counts from SciCor Clinical Laboratories in the 30 days prior to study entry > 300 cells/mm3.

Prior Medication:

Excluded, participation in studies using:

• Dideoxyinosine (ddI).
• 2',3'-Dideoxy-2',3'-didehydrothymidine (d4T).
• Dideoxycytidine (ddC).
• Excluded within one month of study entry:
• Any other experimental antiretroviral compounds.

Patients must:

• Have documented HIV positivity via ELISA.
• Meet CDC criteria for AIDS or AIDS related complex (ARC).
• Have received zidovudine (AZT) for = or > 6 months and tolerated a dose of at least 500 mg per day without significant hematologic toxicity.
• Have no acute AIDS defining opportunistic infection, but may be receiving suppressive therapy for such infections.
• Demonstrate at least one of the following criteria for clinical deterioration despite AZT therapy within 4 weeks prior to study entry (8 weeks prior for weight loss):
• involuntary weight loss of more than 5 percent of the body weight occurring over the 8 week period prior to study entry, Karnofsky score = or > 50 but demonstrating a fall = or > 20 from previous level of functioning (assessment must be persistent on two occasions at least 14 days apart), unexplained fever of = or > 38 degrees C (despite evaluation defined in protocol) for more than 7 days, appearance of newly diagnosed oral hairy leukoplakia or oral candidiasis, or recurrence of a previously quiescent multidermatomal varicella-zoster, appearance of dermatologic afflictions (e.g. psoriasis, molluscum contagiosum, or newly diagnosed seborrheic dermatitis), appearance of chronic herpetic ulcers not responsive to acyclovir therapy.

Required:

• Zidovudine (AZT) for = or > 6 months prior to study entry.