A Phase II Double-Blind Study of Delavirdine Mesylate ( U-90152 ) in Combination With Zidovudine ( AZT ) and/or Didanosine ( ddI ) Versus AZT and ddI Combination Therapy

Inclusion Criteria

Concurrent Medication:

Required:

• PCP prophylaxis for patients with CD4 count <= 200 cells/mm3.

Allowed:

• Topical antifungal agents.
• Oral ketoconazole, fluconazole, and itraconazole for candidiasis or disseminated fungal infections.
• Isoniazid, ethambutol, pyrazinamide, clofazimine, ciprofloxacin, and clarithromycin for acute or maintenance therapy for mycobacterial disease (also clarithromycin for MAC prophylaxis).
• Acute or maintenance therapy for toxoplasmosis.
• Acute or maintenance therapy with acyclovir (no more than 1000 mg/day) for herpes simplex virus infection.
• rEPO and rG-CSF.
• Antibiotics for bacterial infections (except rifampin and rifabutin).
• Antipyretics, analgesics, nonsteroidal anti-inflammatory agents, antiemetics, and methadone.

Concurrent Treatment:

Allowed for cutaneous Kaposi's sarcoma:

• Localized radiation therapy.
• Limited intralesional therapy.

Patients must have:

• HIV infection.
• CD4 count 100 - 500 cells/mm3.
• Prior cumulative monotherapy of <= 6 months (may have taken either AZT or ddI, but not both) OR no prior antiretroviral therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malignancy (other than basal or squamous cell carcinoma of the skin, Stage 1 or 2 cervical intraepithelial neoplasia, or minimal Kaposi's sarcoma).
• Considered to be unlikely to comply with study requirements.

Concurrent Medication:

Excluded:

• Antiretroviral therapies and biologic response modifiers (except for study medications, rEPO, and rG-CSF).
• Rifampin.
• Rifabutin.
• Terfenadine.
• Astemizole.
• Loratadine.
• Quinidine.
• Digitoxin.
• Systemic corticosteroids for more than 21 consecutive days.
• Foscarnet.
• Systemic cytotoxic chemotherapy for a malignancy.

Patients with the following prior conditions are excluded:

• History of intolerance to AZT at <= 600 mg/day or ddI at <= 400 mg/day or discontinuation of either drug for toxicity.
• History of intolerance to trifluoperazine or piperazine citrate (per amendment).
• History of pancreatitis.
• History of grade 2 or worse peripheral neuropathy.
• Unexplained temperature >= 38.5 C on any 7 days within the past 30 days.
• Chronic diarrhea on any 15 days during the past 30 days.

Prior Medication:

Excluded:

• Prior foscarnet as induction or maintenance therapy.
• Prior U-90152.
• Prior ddC or d4T.
• Prior AZT/ddI in combination or taken separately at different times.
• Prior non-nucleoside reverse transcriptase inhibitors (nevirapine, atevirdine, etc.).
• Prior protease inhibitors (although patients from ACTG 282 are eligible).
• HIV-1 vaccine within the past 21 days.
• Acute treatment for a serious infection or for any opportunistic infection within the past 14 days.

Excluded within the past 30 days:

• Interferon or interleukin.
• Rifampin.
• Rifabutin.
• Terfenadine.
• Astemizole.
• Loratadine.
• Recombinant EPO or G-CSF.
• Hydroxyurea.
• SPV-30.
• Any other investigational drug.

Active drug or alcohol use.

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