This study will determine whether highly active antiretroviral therapy (HAART) administered in conjunction with exogenous recombinant human interleukin-2 (rhIL-2) to HIV-infected individuals will be safe and will result in greater increases in CD4+ cells than HAART administered alone. 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 HAART versus HAART 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. 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 will be taken off study. For subjects whose 10 week realtime viral load is >5000 copies/ml the preentry viral load will be determined to assist the physician in decision making regarding subsequent therapy. Subjects who have <5000 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 (9 cycles). Subjects on the CIV rhIL-2 who achieve both a >25% increase and at least a 100 cell/mm3 increase in CD4 count above the prerandomization baseline value after 3 or 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. The proportion of subjects with significant (i.e.>50% increase from time of randomization) increases in CD4 counts will be compared between HAART alone and CIV or SC rhIL-2 after 6 and after 9 cycles of therapy of rhIL-2 (e.g., 60 and 84 total weeks on study). The effect of rhIL-2 on quality of life parameters will also be assessed at several points during the study. A subset of subjects will be evaluated for the effect of rhIL-2 on immune cell phenotypes and function, and HIV viral load and on rate of development of antiviral drug resistance.
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