A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine

Inclusion Criteria

Concurrent Medication:

Required:

• PCP prophylaxis for patients with CD4 count < 200 cells/mm3 or a prior history of PCP.

Allowed:

• Trimethoprim with sulfamethoxazole or dapsone, intravenous pentamidine, atovaquone, primaquine-clindamycin or trimetrexate for acute PCP.
• Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for treatment of mucosal and esophageal candidiasis.
• Prophylaxis or therapy for opportunistic infections, as indicated, with other medications such as itraconazole, isoniazid, pyrazinamide, clofazimine, clarithromycin, azithromycin, ethambutol, amikacin, ciprofloxacin, ofloxacin, pyrimethamine, sulfadiazine, and clindamycin.
• Maintenance therapy for opportunistic infections as long as patients have been on a stable dosage regimen for 1 month prior to study entry.
• Ganciclovir for CMV retinitis or gastrointestinal disease as long as patients have been on a stable dose for at least 1 month prior to study entry with no grade 3 or 4 neutropenia or dependence on G-CSF.
• Acyclovir (<= 1000 mg/day) for maintenance of herpes simplex virus infections.
• Erythropoietin or G-CSF if clinically indicated.
• Antibiotics for bacterial infections unless specifically excluded.
• Rifampin or rifabutin.
• Symptomatic treatments such as antipyretics, analgesics, and antiemetics.

Concurrent Treatment:

Allowed:

• Local radiation therapy.

Prior Medication: Required:

• At least 6 months of prior cumulative nucleoside therapy with AZT, ddI, or ddC, given as monotherapy or in combination.

Patients must have:

• Prior or current documentation of HIV seropositivity by ELISA confirmed by Western blot, positive HIV antigen, or positive HIV culture, or a second antibody test by a method other than ELISA.
• CD4 count <= 350 cells/mm3.
• Prior cumulative nucleoside therapy of >= 6 months.
• Consent of parent or guardian if less than 18 years of age.

Exclusion Criteria

Concurrent Medication:

Excluded:

• Antiretroviral therapies other than study medications.
• Systemic corticosteroids given consecutively for > 21 days.
• Induction or maintenance with foscarnet.
• Systemic cytotoxic chemotherapy for a malignancy.
• Erythromycin.
• Coumadin/warfarin.
• Phenytoin or phenobarbital.
• Amoxicillin/clavulanate acid (Augmentin) or ticarcillin/clavulanate acid (Timentin).

Patients with the following prior conditions are excluded:

• History of pancreatitis.
• History of intolerance to 500 or 600 mg/day AZT or to 400 mg/day ddI tablets or 500 mg/day ddI sachets.
• History of grade 2 or worse peripheral neuropathy.

Prior Medication:

Excluded at any time:

Prior non-nucleoside reverse transcriptase inhibitors (NVP; L697,611; TIBO; atevirdine).

Excluded within 14 days prior to study entry:

• Acute treatment for a serious infection or any opportunistic infection.
• Biologic response modifiers such as interferon and IL-2.
• Erythromycin.
• Coumadin/warfarin.
• Phenytoin or phenobarbital.
• Ticarcillin/clavulanate acid (Timentin) or amoxicillin/clavulanate acid (Augmentin).