A Study of Nevirapine Used Alone or in Combination With AZT in HIV-1-Infected Children

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Monotherapy phase: To evaluate and compare the safety, tolerance, pharmacokinetics, and preliminary activity of nevirapine administered alone in mildly to moderately symptomatic HIV-infected children ages 2 months to less than 18 years; to evaluate and compare the safety, tolerance, and pharmacokinetics of nevirapine in HIV-infected children ages 1 day to less than 2 months. Combination therapy phase: To evaluate and compare the safety, tolerance, pharmacokinetics, and preliminary activity of nevirapine administered in combination with zidovudine (AZT) in mildly to moderately symptomatic HIV-infected children ages 2 months to less than 18 years.

Compounds with reverse transcriptase inhibitory activity that are more potent and less toxic than the nucleoside analogues are needed. Nevirapine (BI-RG-587) has shown in vitro inhibitory activity against HIV-1reverse transcriptase and has shown a synergistic inhibition of HIV-1 replication when combined with zidovudine (AZT) in a plaque reduction assay.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Roxane Laboratories
• Treatments: Nevirapine; Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• IV gammaglobulin therapy.

• Medications for PCP prophylaxis (e.g., TMP / SMX, dapsone, aerosolized and IV pentamidine).

• Fluconazole.

Patients must have:

• HIV infection. A positive Polymerase Chain Reaction (PCR) is not acceptable as the sole evidence of HIV infection. Three out of five children in each age and dose group must have a serum p24 antigen level of 70 pg/ml or greater and/or a plasma viral titer of 50 TCID/ml or greater prior to study entry.

• Ability to be followed by their original trial center for the duration of the trial.

• Consent of parent or guardian.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Lymphocytic interstitial pneumonitis if steroid-dependent or requiring supplemental oxygen or with a pretreatment paO2 < 70 mm Hg.

• Opportunistic or serious bacterial infections within 28 days prior to entry.

• Demonstrated intolerance to zidovudine prior to administration of nevirapine (in patients enrolled in the combination therapy phase of the study).

• CDC classification of P-2D (secondary infectious diseases) and/or P-2E (secondary cancers).

• Pre-existing malignancies.

Concurrent Medication:

Excluded:

• Other approved or investigational antiretroviral agents.

• All other investigational agents (except fluconazole).

• Glucocorticoids and steroid hormones.

• Dicumarol, warfarin, and other anticoagulants.

• Digitoxin.

• Valproic acid.

• Tolbutamide.

• Doxycycline.

• Chloramphenicol.

• Isoniazid.

• Phenobarbital and other barbiturates.

• Hepatotoxic drugs.

Patients with prior participation in this trial are excluded.

Prior Medication:

Excluded:

• More than 6 weeks of prior zidovudine (AZT) therapy or more than 6 weeks of any other antiretroviral therapy.

Excluded within 7 days prior to study entry:

• AZT (in monotherapy groups only).

Excluded within 4 weeks prior to study entry:

• Other approved or investigational antiretroviral agents.

• All other investigational agents.

• Glucocorticoids and steroid hormones.

• Dicumarol, warfarin, and other anticoagulants.

• Digitoxin.

• Valproic acid.

• Tolbutamide.

• Doxycycline.

• Chloramphenicol.

• Isoniazid.

• Phenobarbital and other barbiturates. Active alcohol or drug abuse to impair compliance with the protocol.