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

To determine the safety and anti-HIV activity of delavirdine mesylate ( U-90152 ) in combination with zidovudine ( AZT ) and/or didanosine ( ddI ) versus AZT/ddI combination.

U-90152 has demonstrated anti-HIV activity. Since the combination of this drug with either AZT or ddI has synergistic inhibitory activity against HIV-1 in vitro, and triple therapy appears to have greater inhibitory activity against HIV-1 in vitro than dual therapy, the use of U-90152 in combination with AZT and/or ddI may improve the benefits of these drugs in persons with HIV disease.

U-90152 has demonstrated anti-HIV activity. Since the combination of this drug with either AZT or ddI has synergistic inhibitory activity against HIV-1 in vitro, and triple therapy appears to have greater inhibitory activity against HIV-1 in vitro than dual therapy, the use of U-90152 in combination with AZT and/or ddI may improve the benefits of these drugs in persons with HIV disease.

Patients are randomized to receive U-90152/AZT/ddI, U-90152/AZT, U-90152/ddI, or AZT/ddI for 48 weeks.

Eligibility 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.