A Randomized, Double-Blind, Four-Arm Study Comparing Combination Nucleoside, Alternating Nucleoside, and Triple-Drug Therapy for the Treatment of Advanced HIV Disease (CD4 <= 50/mm3)

• Status: Completed
• Trial end date: 1996-09-01
• Target enrollment: 0
• Participant gender: All

Summary

To determine the relative clinical efficacy of zidovudine ( AZT ) plus didanosine (ddI), AZT plus zalcitabine ( ddC ), AZT alternating monthly with ddI, and AZT/ddI plus nevirapine in HIV-infected patients with advanced disease.

The rapid emergence of resistant HIV strains has been observed in patients receiving monotherapy with a nucleoside analog or non-nucleoside reverse transcriptase inhibitor. Use of combination therapy with two nucleoside drugs or convergent combination therapy with two nucleosides and a non-nucleoside RT inhibitor may minimize the evolution of these resistant HIV strains. Since toxicity is a major problem in patients with advanced disease who are receiving combination nucleoside therapy, alternating the two drugs may provide a way of retaining several benefits of combination therapy while minimizing the increased toxicity.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; Glaxo Wellcome
• Treatments: Didanosine; Nevirapine; Zalcitabine; Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Required:

• PCP prophylaxis.

Allowed:

• Erythropoietin maintenance.

• G-CSF and GM-CSF.

• Prophylaxis for Mycobacterium avium intracellulare.

• Antifungal prophylaxis or treatment with specific drugs.

• Maintenance therapy for opportunistic infection.

• Over-the-counter medications or alternative therapies such as vitamins and herbs.

• Antibiotics as clinically indicated.

• Steroids for < 21 days for acute problems.

• Antipyretics, analgesics, allergy medication, antidepressants, sleep medications, oral contraceptives, or other appropriate medications.

Concurrent Treatment:

Allowed:

• Radiation therapy for cutaneous Kaposi's sarcoma.

• Acupuncture.

Patients must have:

• Documented HIV infection.

• CD4 count <= 50 cells/mm3.

• Either no prior nucleoside therapy OR a history of prior nucleoside therapy in the absence of high-grade intolerance.

• Life expectancy of at least 6 months.

• Consent of parent or guardian if < 18 years of age.

• Normal chest x-ray at baseline or within 6 months prior to study entry in the absence of new pulmonary or cardiac symptoms (per 12/28/94 amendment).

NOTE:

• Patients who withdrew from protocol ACTG 193 therapy prior to activation of ACTG 193A are not eligible.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Abnormal baseline chest x-ray.

• New pulmonary or cardiac symptoms.

• Psychological or emotional problems sufficient to prevent compliance with study medication.

Concurrent Medication:

Excluded:

• Systemic chemotherapy for malignancy.

• Acute or induction therapy for opportunistic infection.

• Antiretroviral drugs other than study drugs.

• Biological response modifiers.

• Erythromycin, phenytoin, phenobarbital, warfarin, or coumadin.

Patients with the following prior conditions are excluded:

• History of recurrent grade 3 or greater toxicity to AZT, ddI, or ddC on two or more occasions.

• Evidence of active pulmonary disease within 6 months prior to study entry.

• History of grade 3 or worse peripheral neuropathy.

• History of acute or chronic pancreatitis.

Prior Medication:

Excluded:

• Prior nevirapine.

Excluded within 7 days prior to study entry:

• Acute therapy for opportunistic infection (maintenance therapy is permitted).

• Acute systemic therapy for a nonopportunistic infection or other medical condition.

• Antiretroviral drugs other than AZT, ddI, or ddC.

• Biological response modifiers.

• d4T therapy.

• Nucleosides other than those used in the study.

• Antibiotics containing clavulanate potassium.

Prior Treatment:

Excluded:

• More than 4 units of blood in a 30-day period.

Active alcohol or drug abuse.