The Safety and Effectiveness of Nevirapine and Zidovudine, Given Separately and Together, in HIV-1 Infected Patients Who Have No Symptoms of the Disease

A Multi-Center, Placebo-Controlled, Double-Blind, Randomized Trial Comparing the Activity, Safety, and Tolerance of 1) 400 Mg Nevirapine in Combination With 500-600 Mg Zidovudine Versus Zidovudine Alone in Asymptomatic HIV-1 Infected Patients With 3-24 Months of Prior Zidovudine Therapy and 200-500 CD4 Cells/mm3 and 2) 400 Mg Nevirapine Versus Nevirapine Placebo in Asymptomatic HIV-1 Nucleoside Naive Patients With 200-500 CD4 Cells/mm3

PRIMARY: To compare the effect of nevirapine versus placebo alone or in combination with zidovudine (AZT) on CD4 T-cell count and percentage after 3 and 6 months of treatment. To evaluate the safety and tolerance of nevirapine alone or in combination with AZT.

SECONDARY: To compare the effects of the various treatment combinations on virologic and immunologic markers.

In Part I, patients who have had prior AZT therapy receive either nevirapine or placebo in combination with AZT. In Part II, patients who are nucleoside naive receive either nevirapine or matching placebo. After 6 months, patients receive open-label nevirapine.

Inclusion Criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis (trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine), at the discretion of the investigator.
• Antifungal prophylaxis with oral fluconazole or ketoconazole.
• Antiviral prophylaxis for herpes simplex virus with <= 1000 mg/day oral acyclovir.
• Dilantin for prevention and treatment of seizures.

Patients must have:

• Asymptomatic HIV-1 infection, with positive serum antibody to HIV-1 as determined by ELISA or Western blot.
• CD4 count 200-500 cells/mm3 within 4-28 days prior to study entry.
• No conditions indicative of AIDS.
• None of the constitutional symptoms that are specifically excluded.
• Prior AZT for 3-24 months (amended 04/04/94) immediately prior to study entry (Part I) OR no prior AZT (Part II).
• Consent of parent or guardian if less than 18 years of age.

NOTE:

• Co-enrollment in a protocol involving another investigational drug or biologic is not permitted.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malignancy other than limited cutaneous basal cell carcinoma.
• Psychiatric condition sufficient to impair compliance with protocol requirements.

Concurrent Medication:

Excluded:

• Investigational drugs other than study drugs.
• Systemic glucocorticoids and steroid hormones.
• Dicumarol, warfarin, and other anticoagulant medications.
• Cimetidine.
• Tolbutamide.
• Doxycycline.
• Chloramphenicol.
• Phenobarbital and other barbiturates.
• Foscarnet.
• Erythromycin.
• Amoxicillin-clavulanate (Augmentin).
• Ticarcillin clavulanate (Timentin).
• Biologic response modifiers (alpha interferon, IL-2, immune modulators).

Patients with the following condition are excluded:

History of other clinically important disease (i.e., one that precludes participation in the study).

Prior Medication:

Excluded:

• Antiretroviral medications other than AZT.

Excluded within 4 weeks prior to study entry:

• Immunosuppressive or cytotoxic drugs or other experimental drugs.
• Systemic glucocorticoids and steroid hormones.
• Dicumarol, warfarin, and other anticoagulant medications.
• Cimetidine.
• Tolbutamide.
• Doxycycline.
• Chloramphenicol.
• Phenobarbital and other barbiturates.
• Foscarnet.
• Erythromycin.
• Amoxicillin-clavulanate (Augmentin).
• Ticarcillin clavulanate (Timentin).
• Biologic response modifiers (alpha interferon, IL-2, immune modulators).

Required (for patients in Part I):

• Prior AZT at 500-600 mg daily for at least 3 months but not more than 24 months immediately prior to study entry.

Chronic use of alcohol or drugs sufficient to impair compliance with protocol requirements.