The primary hypothesis of this study is that there will be a difference between different routes of intermittently administered rhIL-2 (IV vs subcutaneous admininistration) with a highly active antiretroviral regimen compared to highly active antiretroviral therapy alone with respect to the proportion of subjects achieving 50% increase in CD4 counts above pre-randomization baseline values after one year of rhIL-2 and the rate of change in CD4 counts. The study will also test whether there is a difference between the safety, tolerance, and effect on quality of life of these regimensand whether there are measureable changes in immune cell phenotypes and function and on HIV viral load and rate of antiviral drug resistance development when HAART is used in the setting of rhIL-2 compared to HAART alone. Methods: This is a randomized study to ascertain the effect on CD4 response of high dose, intermittently administered rhIL-2 administered by continuous intravenous infusion versus subcutaneous injections in conjunction with highly active antiretroviral therapy versus highly active antiretroviral therapy alone in patients with HIV and CD4 counts of 50- 300 cells/mm3. Subjects must be protease inhibitor therapy naive. All subjects will receive treatment with indinavir and 2 nucleoside analogues; one of which is new to the subject (HAART). Subjects will receive 12 weeks of HAART. At week 10 an HIV RNA by bDNA (real time) will be done by Chiron. Subjects with < 5,000 copies/ml will be continued on study. Subjects with > 5,000 copies/ml will require no further follow-up and should be taken off study. Subjects who have <5,000 copies/ml of HIV RNA will then be randomized to continue HAART alone or HAART with rhIL-2 at either 9 million units by continuous infusion (CIV) for 5 days every 8 weeks for 72 weeks, or 9 cycles, or rhIL-2 at 7.5 million units by subcutaneous injection twice a day for 5 days every 8 weeks for 72 weeks or 9 cycles. Subjects on the CIV rhIL-2 arm who achieve both a 25% increase and at least a 100 cell/mm3 increase in CD4 count above the prerandomization baseline value after 3 cycles or after 6 cycles will switch to rhIL-2 at 7.5 MIU by subcutaneous injection twice a day for 5 days every 8 weeks for the remainder of their treatment course. Results and Future Plans: The study is ongoing and treatment arms remain blinded, therefore study conclusions and significance can not yet be discussed. The study is continuing to enroll patients and will continue to do so until national enrollment goals are met. Significance: Improvement in immune function remains an illusive goal for many patients with HIV infection. This study will aid in developing immune restorative therapies for patients with HIV infection.
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