Effects of Giving Interleukin-2 (IL-2) Plus Anti-HIV Therapy to HIV-Positive Patients With CD4 Cell Counts of at Least 350 Cells/mm3

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of giving IL-2 plus anti-HIV (antiretroviral) therapy to HIV-positive patients with CD4 cell counts (cells of the immune system that fight infection) of at least 350 cells/mm3. This study will also examine the ability of antiretroviral therapy combined with IL-2 to boost the immune system. IL-2, given through injection under the skin, in combination with anti-HIV therapy can increase CD4 cell counts. This study examines 3 doses of IL-2 in order to determine the safest and most effective dose to use.

Detailed Description
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Interleukin-2 administered subcutaneously, in combination with antiretrovirals, results in an increased CD4+ cell count that might impact upon HIV disease progression. A Phase III trial involving large numbers of HIV-positive patients is the next step in the development process. To develop appropriate clinical experience with this combination, this Phase II trial will allow administration of IL-2 plus antiretroviral therapy to a small number of patients in sites being considered for the Phase III trial. Patients receive antiretrovirals alone or antiretrovirals plus IL-2 given subcutaneously. Three doses of IL-2 are studied, with 12 patients evaluated at each dose. When at least 9 of the first 12 patients complete the 5-day dosing period without dose-limiting toxicity, the next 12 patients are treated at the next highest dose every 12 hours for 5 days every 8 weeks; when this dose is tolerated, the last 12 patients randomized receive the highest study dose every 12 hours for 5 days every 8 weeks. Patients enrolled at the first two doses of IL-2 who complete three courses of treatment have their dose escalated to a maximum of the highest study dose.

Official Title
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A Randomized, Open Label Phase II Study of Subcutaneous Interleukin-2 (Proleukin) Plus Antiretroviral Therapy vs. Antiretroviral Therapy Alone in Patients With HIV Infection and at Least 350 CD4+ Cells/mm3

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Aldesleukin
* Drug: ART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients may be eligible for this study if they: Are HIV-positive. Have a CD4 cell count greater than or equal to 300 cells/mm3. Have no AIDS-defining illnesses. Are at least 18 years old. Have been on antiretroviral therapy for at least 7 days prior to study entry. Exclusion Criteria Patients will not be eligible for this study if they: Abuse alcohol or drugs, or have any serious psychiatric or medical illnesses that would affect their safety or ability to complete the study. Have a history of cancer (other than Kaposi's sarcoma), an AIDS-defining illness, a central nervous system abnormality, or an autoimmune/inflammatory disease. Are pregnant or breast-feeding. Have ever received IL-2.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will be broken into 3 groups. Each group will receive ART and escalating doses of aldesleukin. All participants will then receive that maximum tolerated dose of aldesleukin. | Drug: Aldesleukin<br>* Il-2<br>Drug: ART<br>* antiretroviral therapy for the treatment of HIV<br>|
| Active Comparator: 2<br>All participants will receive ART | Drug: ART<br>* antiretroviral therapy for the treatment of HIV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 count |  | Throughout study | 
| Laboratory and clinical adverse events |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Injections, Subcutaneous, Interleukin-2, Dose-Response Relationship, Drug, Drug Therapy, Combination, CD4 Lymphocyte Count, Anti-HIV Agents