A Phase III, Randomized, Double-Blind, Multicentre Study to Evaluate the Safety and Efficacy of 1592U89 in Patients With AIDS Dementia Complex

Inclusion Criteria

Patients must have:

• Documented HIV infection.
• Evidence of HIV - associated dementia.
• Been on stable antiretroviral treatment for a minimum of 6 weeks prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms or conditions are excluded:

• Debilitated as a result of their HIV disease, associated illness or therapies who the investigator determines will not be able to complete the 12 week randomized dosing period.
• Memorial Sloan-Kettering (MSK) score of >= 3 for dementia.
• Confounding neurological diseases which may interfere with interpretation of neurological and neurophysical assessments.
• Malabsorption syndrome or other gastrointestinal dysfunction which renders them unable to take oral medication.
• Chronic diseases such as diabetes, congestive heart failure, cardiomyopathy, other cardiac dysfunctions, etc., which in the investigator's opinion would compromise the safety of the patient.
• Symptomatic AIDS-defining opportunistic infection not responsive to therapy.

Concurrent Medication:

Excluded:

• Treatment with cytotoxic chemotherapeutic agents within the first 12 weeks of the study.
• Treatment with nerve growth factor within the first 12 weeks of study.
• The use of narcotic analgesics, sedatives, benzodiazepines, antidepressants, anti-psychotic agents and other psychoactive drugs which would interfere with the assessment of the neurological and neurophysical status of the patient.
• Use of stavudine (d4T) during the first 12 weeks of the study.
• Immunomodulating agents (except GM/G-CSF or epoietin).
• Psychoactive drugs (at the investigator's discretion).

Concurrent Treatment:

Excluded:

• Treatment with radiation therapy within the first 12 weeks of the study.

NOTE:

• With the exception of local treatment for Kaposi's sarcoma.

Patients with any of the following prior conditions are excluded:

• Previous neurological disease unrelated to HIV infection.
• History of clinically apparent hepatitis within the last 6 months.
• History of clinically apparent pancreatitis in the last 6 months.

Prior Medication:

Excluded:

• Treatment with cytotoxic chemotherapeutic agents within 1 month of entry.
• Participation in investigational antiretroviral trials within the past 3 months.
• HIV vaccine within the past 3 months.
• Treatment with immunomodulating agents such as systemic corticosteroids, interleukins, thalidomide, anticytokine agents, anti-oxidants or interferons within 1 month of study entry.
• Nerve growth factor.

Prior Treatment:

Excluded:

• Treatment with radiation therapy within 1 month of entry.

NOTE:

• With the exception of local treatment for Kaposi's sarcoma.

Risk Behavior:

Excluded:

Current alcohol or illicit drug use which may interfere with the patient's ability to comply with the study protocol.

Required:

• Stable antiretroviral treatment that has been ongoing for a minimum of 6 weeks prior to study entry, may or may not include ZDV.

Required:

• Stable antiretroviral treatment for a minimum of 6 weeks prior to study entry.