Clinical trial NCT00110812
Conditions: HIV Infections
Keywords: Treatment Naive IL-2 rIL-2
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2005-09-01; Completion date: 2011-02-01
Enrollment: 267 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the effect of short cycles of recombinant interleukin-2 (also known as rIL-2 or aldesleukin) given with or without anti-HIV drugs in HIV infected patients. The effects will be compared with a study group that receives no IL-2 or antiretroviral therapy.

Study hypothesis: Intermittent aldesleukin, when given without antiretroviral therapy to patients with early HIV infection, will produce no change in HIV viral load and increases in CD4+ T lymphocyte counts comparable to aldesleukin administered with antiretrovirals.

Detailed description:
Highly active antiretroviral therapy (HAART) has dramatically improved prognosis and lowered morbidity and mortality rates for HIV infected patients. However, significant drug toxicities, difficulties with patient compliance to HAART regimens, and development of drug resistance highlight the need for less toxic, immune-based strategies. Aldesleukin is a synthetic protein that can increase CD4 counts; it is currently approved by the Food and Drug Administration (FDA) for use in patients with metastatic melanoma and renal cell carcinoma. Previous studies of aldesleukin in HIV infected patients indicated that increased CD4 counts can persist for years after aldesleukin administration, and aldesleukin given with HAART may also lead to significant lowering of viral load. This study will examine the immunologic effects of intermittent cycles of aldesleukin administered with and without HAART as compared to no therapy in HIV infected patients.

This study will last approximately 31 months. Participants will be randomly assigned to one of three groups at study entry. Group A will receive no aldesleukin or HAART. Group B will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level. Group C will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; Group C participants will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle). HAART will not be provided by the study. Some Group B and C participants may take part in additional cycles of aldesleukin if they meet certain study criteria.

All participants in this study will have at least 8 study visits; these visits will occur at study entry and Weeks 4, 8, 12, 16, 20, 24, and 32. Blood collection will occur at all visits and will include tests for CD4 count and viral load. Groups B and C will have additional blood collection within 4 days prior to the start of each aldesleukin cycle. On the last day of each aldesleukin cycle, Groups B and C will be assessed for toxicities, adverse events, and adherence to the aldesleukin daily injections; they will also have another blood collection. Group C participants will have an additional blood collection for HIV genotyping after they have completed their third aldesleukin cycle. Extended follow-up visits will occur approximately every 4 months for an additional two years. Blood collection will occur at these visits and will include tests for CD4 count, viral load, and other laboratory tests.

Arms: arm 1: Participants will receive no aldesleukin or HAART arm 2: Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level. Some Group 2 participants may take part in additional cycles of aldesleukin if they meet certain study criteria. arm 3: Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; Group 3 participants will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle). Some Group 3 participants may take part in additional cycles of aldesleukin if they meet certain study criteria. HAART is not supplied by the study, and choice of drugs is left to the participant and physician. The HAART regimen should include at least one protease inhibitor and at least 2 nucleoside/nucleotide reverse transcriptase inhibitors.
Interventions: intervention 1: IL-2
Intervention descriptions: intervention 1: 7.5 MIU injected intramuscularly; one arm uses Proleukin together with HAART of choice (protease inhibitor and at least 2 nucleoside/nucleotide reverse transcriptase inhibitors)

Protocol documents: