A Phase I Concentration-Targeted Multidose Study of Atevirdine Mesylate ( U-87201E ), AZT, and ddI or ddC

Inclusion Criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis with pentamidine, TMP/SMX, or dapsone (if appropriate).
• Clotrimazole troches or nystatin oral suspension for oral candidiasis.
• Acyclovir (up to 1000 mg/day) for herpes lesions.
• Supportive care as deemed necessary for toxicities .

Patients must have:

• HIV infection.
• CD4 count <= 500 cells/mm3.
• No active opportunistic infections.
• Consent of parent, guardian, or person with power of attorney, if less than 18 years of age.

NOTE:

• Participation of women in the study is encouraged.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Acute medical problems, including opportunistic infections (e.g., active cryptococcosis, Pneumocystis carinii, herpes zoster, histoplasmosis, and CMV) or nonopportunistic diseases (e.g., liver or renal disease or lymphoma).
• Current diagnosis of malignancy for which systemic therapy would be required during the study.
• Active gastrointestinal disorders.

Concurrent Medication:

Excluded:

• Investigational drugs.
• Systemic therapy for malignancy.
• Phenobarbital, phenytoin, ketoconazole, rifampin, rifabutin, cimetidine, beta blockers, chronic antacids, antiarrhythmic agents, or other medications known to affect cardiac conduction or seizure threshold.

Patients with the following prior conditions are excluded:

• History of any cardiovascular disease, including conduction disturbances, arrhythmias or atherosclerotic heart disease.
• History of CNS disease such as seizure disorder, AIDS Dementia Complex, progressive multifocal leukoencephalopathy, or any other active neurological disorder.
• History of chronic gastrointestinal disorders such as chronic diarrhea (> 4 weeks duration).

Prior Medication:

Excluded:

• Antiretroviral or immunomodulator agents (such as AZT, ddI, ddC, interferon, etc.) within 15 days prior to study entry.
• Cytotoxic chemotherapy within 1 month prior to study entry.
• Prior U-87201E or other non-nucleoside reverse transcriptase inhibitors (i.e., nevirapine, TIBO, L697,661).

Present use of alcohol or illicit drugs.