Interleukin-2 Augmentation of Specific Anti-HIV Immune Responses: Phase I Trial of the Combination of 3'-Azido-3'-Deoxythymidine (Zidovudine) and Recombinant Interleukin-2 in Patients With Asymptomatic HIV Infection Associated With Lymphadenopathy (Walter Reed Stage II)
Zidovudine
+ Aldesleukin
Blood-Borne Infections+15
+ Urogenital Diseases
+ Genital Diseases
Treatment Study
Summary
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. Five patients who have already received and tolerated oral AZT for at least 8 weeks continue their AZT treatment and at the same time receive IL-2 on a schedule of 5 days on the drug, 2 days off the drug. The IL-2 is administered by 30-minute intravenous (IV) infusion according to this schedule for 4 weeks. The first week of IL-2 treatment is on an inpatient basis and the remaining 3 weeks are on an outpatient basis. Toxicity is monitored every week. Maximum tolerated dose (MTD) is defined as the maximum dose at which 3 out of 5 patients experience Grade 3 or above toxicity during the course of IL-2 administration. A second cohort of five patients will receive IV IL-2. If the MTD is not reached, five additional patients will receive IV IL-2. All five patients in a given cohort must complete a full 4-week course of IL-2 before subsequent patients are entered at the next higher dose level. After IV dosing is completed at these three levels, additional 5-patient cohorts receive subcutaneous (SC) IL-2 according to the same schedule. Each patient is restricted to one dosage group. Patients are treated and followed for a total of 24 weeks. Patients receive ibuprofen for fever and chills.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.30 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Duke Univ. Med. Ctr. Adult CRS
Durham, United StatesOpen Duke Univ. Med. Ctr. Adult CRS in Google Maps