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

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

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

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.

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.

Injections, Subcutaneous, Interleukin-2, Dose-Response Relationship, Drug, Drug Therapy, Combination, CD4 Lymphocyte Count, Anti-HIV Agents

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.

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.