The objectives of this study are as follows; 1) to determine the safety of the tolerated dose of rIL-2 when given to a larger number of HIV-infected children, 2) to determine the effect of rIL-2 administration on antigen-and mitogen-induced lymphocyte proliferation and on cytotoxic T and natural killer cell responses, 3) to determine the effect of rIL-2 administration on expression of HLA-DR on CD4 and CD8 cells, 4) to determine the effect of rIL-2 administration on viral load, 5) to determine the effect of rIL-2 administration on the number of naive and memory CD4 and CD8 cells, natural killer cells, and the T-cell receptor repertoire, 6) to determine the effect of rIL-2 administration on apoptosis of peripheral blood mononuclear cells, 7) to determine the effect of rIL-2 administration on JAK3 expression in PBMC. Background: In children with HIV infection, loss of immune function is thought to contribute to disease progression. A progressive loss of lymphocyte function, as measured by lymphocyte proliferation responses to mitogens, alloantigens, and antigens, has been detected in HIV-infected children. In addition, children wth advanced disease frequently have CD4 cell counts that are lower than normal for age. CD4 counts below certain levels are associated with a higher risk of infection with opportunistic organisms, suh as Pneumocystis carinii and Mycobacterium avium complex. Restoration of immune function in HIV-infected children is a highly desirable goal. Such restoration might lead to reductions in viral load. Among the options available for immunotherapy, cytokine replacement therapy is particularly attractive, since a number of recombinant cytokines are available, some of which have already been tested in small numbers of HIV-infected adults. Replacement therapy with interleukin-2 (IL-2) is a good option for several reasons: 1) antigen-specific helper T cell responses were corrected in vitro by addition of recombinant IL-2 (rIL-2) to lymphocyte cultures of children with HIV infection; 2) IL-2 plays key role in the generation of helper and cytotoxic T cell responses; 3) encouraging data are available on the use of IL-2 in HIV-infected adults. Based on these observations, the investigators hypothesize that administration of rIL-2 to HIV-infected children will enhance immunological responses against HIV.
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