The Safety and Effectiveness of Zidovudine in the Treatment of Patients With Early AIDS Related Complex

The Safety and Efficacy of Zidovudine in the Treatment of Patients With Early AIDS Related Complex

To determine the safety and usefulness of zidovudine (AZT) for the treatment of patients with early symptomatic HIV infection or early AIDS related complex (ARC). The ability of AZT to suppress HIV, to improve body defenses, and to prevent the occurrence or development of AIDS or advanced ARC is being evaluated.

In one human study, patients with AIDS or advanced ARC who received AZT had fewer life-threatening infections, improved in weight and performance, and lived longer than patients who received a placebo (inactive medication). Further studies are needed because toxic effects associated with the use of AZT were noted and the long-term effectiveness and toxicity of AZT are still unknown. It is also unknown if AZT will benefit patients with less severe HIV infections such as early ARC or PGL.

In one human study, patients with AIDS or advanced ARC who received AZT had fewer life-threatening infections, improved in weight and performance, and lived longer than patients who received a placebo (inactive medication). Further studies are needed because toxic effects associated with the use of AZT were noted and the long-term effectiveness and toxicity of AZT are still unknown. It is also unknown if AZT will benefit patients with less severe HIV infections such as early ARC or PGL.

Patients accepted into the study are randomly assigned to receive either AZT or placebo. Treatment continues for a minimum of 104 weeks beyond the time the last patient enters the study. If the study medication causes toxic effects, the dose is decreased or temporarily stopped, and if the toxic effects are severe, then the medication will be stopped permanently. Participants visit the clinic every 2 weeks during the first 16 weeks and once a month thereafter. Throughout the study frequent blood samples are taken to monitor the effectiveness and safety of the treatment. AMENDED: The placebo arm has been discontinued as of August 3, 1989 and the AZT dose has been reduced.

Inclusion Criteria

• Patients must have a positive antibody to HIV confirmed by a federally licensed ELISA test kit.
• The CD4 cell count must be 201 - 799 cells/mm3 measured on two separate occasions within 60 days at least 72 hours apart prior to study entry (at least 1 of 2 counts and the mean must be < 800 cells/mm3, and at least 1 of 2 counts and the mean must be > 200 cells/mm3). The last count must be within 14 days of study entry.

Concurrent Medication:

Allowed:

• Acetaminophen and acetaminophen products but use should be minimized. Continuous use for > 72 hours is discouraged.
• Aerosolized pentamidine.

Prior Medication:

Allowed:

• Chemoprophylaxis for Pneumocystis carinii pneumonia with aerosolized pentamidine of 300 mg every 4 weeks through the Respirgard II nebulizer if patient has CD4(+) count < 200 cells/mm3 measured on 2 determinations at least 48 hours apart.

Exclusion Criteria

Concurrent Medication:

Excluded:

• Other antiretroviral agents, biologic modifiers or corticosteroids.
• Other experimental medications.
• Systemic chemoprophylaxis of Pneumocystic carinii pneumonia (PCP) - aerosolized pentamidine is allowed.

Prior Medication:

Excluded:

• Zidovudine (AZT).
• Other antiretroviral agents.
• Excluded within 30 days of study entry:
• Biologic modifiers or corticosteroids.
• Excluded within 60 days of study entry:
• Ribavirin.

Prior Treatment:

Excluded within 30 days of study entry:

• Blood transfusions.

Patients may not have any of the following diseases or symptoms:

• Active oral candidiasis at entry.
• An opportunistic infection or malignancy fulfilling the definition of AIDS (CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome).
• Temperature > 38.5 degrees C persisting for > 14 consecutive days or > 15 days in a 30-day interval present at entry.
• Chronic diarrhea defined as = or > 3 liquid stools per day, persisting for > 14 days without a definable cause during the past 2 years.
• HIV neurologic disease as manifested by motor abnormalities including impaired rapid eye movements or ataxia; motor weakness in the lower extremities; sensory deficit consistent with a peripheral neuropathy; bladder or bowel incontinence.
• Concurrent neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix.
• Subjects with hemophilia should be evaluated and treated under the hemophilia protocols, if available at that ACTG.

Patients may not have any of the following diseases or symptoms:

• Active oral candidiasis at entry.
• An opportunistic infection or malignancy fulfilling the definition of AIDS (CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome).
• Temperature > 38.5 degrees C persisting for > 14 consecutive days or > 15 days in a 30-day interval present at entry.
• Chronic diarrhea defined as = or > 3 liquid stools per day, persisting for > 14 days without a definable cause during the past 2 years.
• HIV neurologic disease as manifested by motor abnormalities including impaired rapid eye movements or ataxia; motor weakness in the lower extremities; sensory deficit consistent with a peripheral neuropathy; bladder or bowel incontinence.
• Concurrent neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix.
• Subjects with hemophilia should be evaluated and treated under the hemophilia protocols, if available at that ACTG.

Active drug or alcohol abuse.