The Safety and Effectiveness of Nevirapine Plus Lamivudine Plus Other Anti-HIV Drugs

An International, Double Blind, Randomized, Phase III Study to Evaluate the Tolerance, Safety, and Effectiveness of Viramune (Nevirapine) in Preventing Clinical AIDS Progression Events or Death When Used in Combination With Lamivudine (3TC) and Stable (>= 4 Weeks) Background Nucleoside Therapy

To evaluate the tolerance, safety, and effectiveness of Viramune in preventing clinical AIDS progression events or death when used in combination with Lamivudine and background nucleoside therapy.

Eligible patients will be randomized to treatment with either 1) open-label 3TC twice daily plus Viramune once daily for 2 weeks and then with Viramune twice daily; or 2) open label 3TC twice daily plus Viramune placebo once daily for 2 weeks and then twice daily Viramune. Patients will start Viramune and 3TC on study day 0. Patients will be evaluated for development of AIDS progression events at months 1, 2, 3, and 4, and every 2 months thereafter until 18 months after the last patient is enrolled or 24 months, whichever occurs first.

Inclusion Criteria

Patients must have:

• Documented HIV infection.
• CD4+ cell count <= 200 cells/mm3.
• Life expectancy > 3 months.
• Written informed consent from parent or guardian for patients < 18 years of age.
• Willingness and ability to follow protocol requirements.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following conditions or symptoms are excluded:

Patient is enrolled or plans to enroll during the course of this study in another clinical study of an antiretroviral or other agent used to treat HIV-1 infection.

• NOTE:
• Patients are allowed to participate in opportunistic infection clinical studies if the investigational agent is not contraindicated for the study.

Concurrent Medication:

Excluded:

• Patient is receiving therapy with an antiretroviral agent other than ZDV, d4T, ddI, ddC, or 3TC.
• Patient is receiving acute therapy for a clinical AIDS progression event such as systemic chemotherapy.
• Dicumarol, Warfarin and other anticoagulant medications.
• Tolbutamide.
• Investigational drugs (unless included in opportunistic infection clinical trial) and all antiretroviral agents (excluding ZDV, ddC, ddI, d4T and 3TC).
• Neurotoxic drugs.
• Cimetidine.
• Erythromycin.

Concurrent Treatment:

Excluded:

Radiation therapy.

Patients with any of the following prior conditions and symptoms are excluded:

History of clinically important disease other than HIV-1 infection or related diseases that, in the opinion of the investigator, may put the patient at risk because of participation in this study.

Prior Medication:

Excluded:

• Patient has received prior therapy with Viramune or any other non-nucleoside reverse transcriptase inhibitor.
• Patient has received any immunosuppressive or cytotoxic drugs or any other experimental agent within 4 weeks prior to study day 1.
• Patient has received treatment with erythromycin, coumadin/warfarin, phenobarbital, amoxicillin/clavulanic acid, or ticarcillin/clavulanic acid within 2 weeks prior to study day 0.

Risk Behavior:

Excluded:

Patients who are active chronic alcohol or substance abusers or have an active psychiatric condition sufficient to impair compliance with protocol requirements.

Required:

Patient must be receiving stable nucleoside therapy with at least one agent for >= 4 weeks prior to study day 0. Zidovudine (ZDV), Zidovudine + Dideoxycytidine (ddC), or Zidovudine + Didanosine (ddI) must be used unless prior intolerance precludes ZDV use. Stable use means no change in dose > 50% for any background nucleoside within four weeks prior to study day 0.

NOTE:

• If patient is ZDV intolerant, ddC, ddI or D4T monotherapy is allowed.