Interleukin-2 (IL-2) Treatment for HIV Infected Patients Who Have Interrupted Their Anti-HIV Drug Therapy

An Exploratory, Open-Label, Randomized Trial to Evaluate the Ability of Interleukin-2 (IL-2) to Enhance HIV-Specific Immunity and Influence the Time to Virologic Relapse Following Withdrawal of Potent Antiretroviral Therapy

When an HIV infected person taking strong anti-HIV drugs temporarily stops taking them, viral load rises and the body's immune system is exposed to more HIV. This may lead to the body mounting a better immune response against the virus. The purpose of this study is to find out if taking interleukin-2 (also called IL-2 or aldesleukin) while stopping anti-HIV drugs for short periods of time can help patients control their HIV viral load.

Study hypothesis: Patients in this study will have lower virologic rebound and will maintain their CD4 cell counts for a longer time than other patients in comparative studies.

Structured treatment interruptions (STIs) may stimulate an anti-HIV immune response. Evidence suggests that IL-2, which increases CD4 counts, could also enhance specific immune responses to HIV. Enhanced immune responses could influence the magnitude of and the time to virologic rebound following treatment discontinuation. This study will compare the viral loads present after 12 weeks of an antiretroviral therapy (ART) interruption period between patients who have received different dosing regimens of IL-2 and have taken part in at least two STIs.

This study will last 40 to 104 weeks. IL-2 is provided as part of this study; potent ART is not provided. Patients in this study will receive potent ART with at least two scheduled potent ART interruptions. Patients will be randomly assigned to one of two treatment arms. Arm A patients will receive low-dose injections of IL-2 for 3 weeks, during the last 2 weeks of potent ART interruption periods and the first week of restarting potent ART. Arm B patients will receive high-dose injections of IL-2 during the first 5 days of restarting potent ART after the interruption period. The first two ART interruptions are 4 weeks in duration, followed by 12 weeks back on ART. Depending on the patient's viral load and CD4 count at Week 32, patients will either enter a third potent ART interruption for 12 to 48 weeks or will continue ART. No IL-2 will be given with the third scheduled potent ART interruption. Throughout the study, participants will have physical exams and laboratory tests, including measurements of viral load and CD4 count.

Note: ACTG A5132 closed to accrual on 11/01/04.

Inclusion Criteria:

• HIV infected
• CD4 cell count of 300 cells/mm3 or more within 30 days prior to study entry
• HIV viral load of less than 50 copies/ml within 30 days prior to study entry
• Anti-HIV drug regimen of at least 3 anti-HIV drugs for at least 6 months immediately prior to study entry
• Documented pretherapy plasma HIV viral load measured within 6 months of starting ART
• Willing to use acceptable methods of contraception

Exclusion Criteria:

• HIV viral load of 50 copies/ml or more within 60 days before study entry
• Current use of experimental anti-HIV drugs other than FDA sanctioned investigational drugs
• Abacavir as part of anti-HIV regimen within 8 weeks prior to study entry
• Pregnant or breastfeeding
• History of autoimmune disease, except for stable autoimmune thyroid disease
• Heart problems or on certain medications for treatment of heart problems
• Cancer requiring chemotherapy
• Untreated thyroid disease
• Disease of the central nervous system that has been active within 1 year prior to study entry
• Uncontrolled diabetes
• Allergies to the study medications
• Other illnesses that would make it inappropriate for patients to participate in the study
• Immunomodulatory therapy within 4 weeks prior to study entry
• Hydroxyurea within 6 months prior to study entry
• Drug or alcohol use that, in the opinion of the investigator, would interfere with the study
• Psychiatric or mental impairment that would affect compliance