A Study of Zidovudine Plus Interleukin-2 in HIV-Infected Patients Who Have No Symptoms of Infection But Who Have Tender Lymph Nodes

• Status: Completed
• Trial end date: 1995-02-01
• Target enrollment: 0
• Participant gender: All

Summary

AMENDED: To investigate whether subcutaneous (SC) injection of IL-2 produces biological responses which parallel those observed with IV dosing. Original design: To evaluate the short-term effects of combined administration of zidovudine (AZT) and increasing doses of recombinant interleukin-2 (aldesleukin; IL-2) in patients infected with HIV, who have lymphadenopathy, but who are otherwise asymptomatic (no other symptoms). The first phase of this clinical trial will establish maximum tolerated dose ( MTD ). How quickly the drugs get into the blood and how long they remain there (pharmacokinetics) will also be studied at each dose as well as the effect on HIV.

Since AZT has no effect on cells that contain inactive virus (latently infected cells) and these cells may act as viral reservoirs, that a second agent that can destroy these infected cells would be useful in combination with AZT. The different activities of AZT and IL-2, as well as the non-overlapping nature of their mechanisms of action and toxicity, increase the theoretical benefits of combining AZT, a drug which has clinically significant activity in HIV-related disease but cannot eliminate infected cells, with IL-2, a drug which may enhance anti-HIV immunity, destroy chronically infected cells, and allow immune recognition of latently infected cells.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Aldesleukin; Interleukin-2; Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Necessary topical agents, including nystatin or clotrimazole, as well as acyclovir. Patients on medications without which the patient would be placed at significant risk (seizures, diabetic control, respiratory embarrassment) may continue only at the discretion of the study pharmacologist.

Patients must have:

• Asymptomatic HIV infection associated with lymphadenopathy.

• Walter Reed Stage II disease, with positive antibody to HIV confirmed by Western blot test.

Exclusion Criteria

Co-existing Condition:

Patients will be excluded from the study for the following:

• Development of a disease requiring a drug which might potentiate toxicity of the study drugs or a drug likely to have antiretroviral effect.

• Active opportunistic infection.

• Major organ allograft.

• Significant cardiac or pulmonary disease or central nervous system (CNS) lesions.

Concurrent Medication:

Excluded:

• Ongoing therapy for an opportunistic infection.

• Beta-blockers.

• Antihypertensive medication other than diuretics.

• All nonessential medication including pain medications.

Patients without interleukin 2 (IL-2) augmentable anti-HIV antibody-dependent cellular cytotoxicity (ADCC) or or cell-mediated cytotoxicity (CMC) in vitro are excluded.

Prior Medication:

Excluded within 12 weeks of study entry:

• Other antiretroviral agents (patients with CD4 counts of 400 - 500 per mm3 who are receiving AZT may continue to receive it until study treatment is initiated).

• Immunomodulators.

• Corticosteroids.

• Other experimental therapy.

• Antineoplastic chemotherapy.

Active drug or alcohol abuse.