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 nitrogens, alloantigens, and antigens, has been detected in HIV-infected children. Such functional loss of activity may be associated with an increased risk of severe or life-threatening infection. In addition, children with advanced disease frequently have CD4 cell counts that are lower than normal for age. CD4 cell counts below certain levels are associated with a higher risk of infection with opportunistic organisms, such 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 reduction in viral load. In addition, the risk of developing secondary infections might be reduced. 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 particularly attractive 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 a key role in the generation of helper and cytotoxic T cell responses; and 3) encouraging data are available on the use of IL-2 in HIV-infected adults. Based on these observations, we hypothesize that administration of rIL-2 to HIV-infected children will enhance immunological responses against HIV. This study aims to determine the safety of the tolerated dose of rIL-2 when given to a larger number of HIV-infected children. In addition, the study aims to determine the effect of rIL-2 administration on antigen and nitrogen induced lymphocyte proliferation and on cytotoxic T and natural killer cell responses. Also, the study aims to determine the effect of rIL-2 administration on viral load and on expression of HLA-DR on CD4 and CD8 cells, natural killer cells, and the T-cell receptor repertoire.
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