The Safety and Effectiveness of Retrovir Plus HIVID Combined With Either Nevirapine or Invirase in the Treatment of HIV Infection

Administration of three-drug combinations for treatment of HIV infection is preferred over monotherapy or duotherapy. A system has been designed to rapidly evaluate current multidrug combinations of antiretrovirals and allow the addition of new agents as they become available.

Patients are randomized to receive AZT/ddC either alone or in combination with nevirapine or Ro 31-8959 for a minimum of 48 weeks. Patients are followed at weeks 2 and 4 and every 4 weeks thereafter.

Inclusion criteria

Concurrent Medication:

Encouraged:

• PCP chemoprophylaxis for patients whose CD4 count falls below 200 cells/mm3 or who develop PCP on study.

Allowed:

• Secondary prophylaxis with nonexperimental agents in patients who develop TB, Mycobacterium avium-intracellulare, toxoplasmosis, histoplasmosis, cryptococcosis, disseminated candidiasis, or cytomegalovirus infection.
• Acyclovir for 21 days or less for acute treatment.
• Recombinant erythropoietin and G-CSF for grade 3 or worse anemia and neutropenia, respectively.

Patients must have:

• HIV infection.
• CD4 count 200 - 500 cells/mm3.
• No prior antiretroviral therapy.
• Life expectancy of at least 48 weeks.
• Consent of parent or guardian if less than 18 years of age.

NOTE:

• Participating centers are encouraged to enroll female patients.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Any grade 3 or greater toxicity.
• Symptoms of peripheral neuropathy.
• Malabsorption or severe chronic diarrhea.
• Inability to eat at least one meal daily because of chronic nausea, emesis, or abdominal or esophageal discomfort.

Concurrent Medication:

Excluded during the first 28 days of nevirapine administration:

• Augmentin and other antibiotics containing clavulanic acid.

Excluded at any time:

• Dicumarol, warfarin, and other anticoagulant medications.
• Tolbutamide.
• Cimetidine.
• Erythromycin.

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis.
• History of grade 2 or worse peripheral neuropathy from any cause.

Prior Medication:

Excluded:

• Any prior antiretroviral therapy.

Excluded within 4 weeks prior to study entry:

• Immunomodulating agents such as systemic corticosteroids, IL-2, alpha-interferon, beta-interferon, or gamma-interferon.
• Immunotherapeutic vaccines.
• Cytotoxic chemotherapy.
• Erythromycin.
• Dicumarol, Coumadin / warfarin, and other anticoagulant medications.
• Phenobarbital.
• Amoxicillin / clavulanate.
• Ticarcillin / clavulanate.
• Tolbutamide.
• Erythromycin.
• Cimetidine.

Prior Treatment:

Excluded within 4 weeks prior to study entry:

• Non-local radiation therapy. Current alcohol or illicit drug use that would interfere with ability to comply with study requirements.