Randomized, Phase I/II, Dose-Ranging, Open-Label Trial of the Anti-HIV Activity of Delavirdine Mesylate (DLV; U-90,152S)

Inclusion Criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis.
• Topical antifungal agents, clotrimazole troches, nystatin oral suspension, topical ketoconazole, and oral fluconazole.
• Acyclovir (<= 1000 mg/day) as maintenance therapy for herpes simplex virus.
• Recombinant erythropoietin and G-CSF.
• Antibiotics for bacterial infections, unless specifically excluded.
• Symptomatic treatment such as antipyretics, analgesics, nonsteroidal anti-inflammatory agents, and antiemetics.
• Antacids.

Patients must have:

• HIV-1 infection.
• CD4 count 200 - 500 cells/mm3.
• Either no prior antiretroviral therapy or discontinued AZT monotherapy 3 or more weeks prior to study entry.

NOTE:

• Half of patients should be antiretroviral naive.

Prior Medication:

Allowed:

• Prior AZT.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malignancy other than minimal Kaposi's sarcoma.

Concurrent Medication:

Excluded:

• Rifabutin.
• Rifampin.
• Terfenadine.
• Astemizole.
• Loratadine.
• Trifluoperazine.
• Piperazine citrate.
• Any acute or chronic therapy for CMV, MAC, toxoplasmosis, or disseminated fungal infection.
• Non-study antiretroviral therapies, interferons, biologic response modifiers, and HIV vaccines.
• 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 pancreatitis (in patients who received prior AZT).
• History of grade 2 or worse peripheral neuropathy (in patients who received prior AZT).
• History of hypersensitivity to BHAP compounds (e.g., trifluoperazine - Stelazine, piperazine citrate - Antepar).

Prior Medication:

Excluded within 30 days prior to study entry:

• Any investigational medication.
• Interferon.
• Interleukin.
• Rifabutin.
• Rifampin.
• Terfenadine.
• Astemizole.
• Loratadine.
• Trifluoperazine.
• Piperazine citrate.

Excluded at any time:

• Prior ddI, ddC, d4T, or 3TC.
• Prior foscarnet.
• Prior BHAP compound or other non-nucleoside RT inhibitor.

Active substance abuse interfering with compliance.

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