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

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.