Interleukin 2 as Immune Therapy in Early HIV Infection

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EXCEED THE SPACE PROVIDED. This is a revised application for a proposal to conduct a prospective, randomized trial of daily, low-dose administration of lnterleukin 2 (1L2) in the treatment of early HIV infection (i.e., infection that was identified, and treated with highly active antiretroviral therapy (HAART), soon after establishment of infection). The long-range of this research is to develop treatments for HIV infection that minimize the need for chronic therapy with antiretroviral medications. The major hypothesis to be tested in this application is that Interleukin 2 (IL2) given with highly active antiretroviral therapy (HAART) will enable the host immune system to suppress HIV replication more effectively than will HAART alone. This hypothesis will be tested by administering low doses of IL2 subcutaneously daily to a population of subjects whose HIV infection was diagnosed, treated with HAART, and suppressed to undetectable levels in the blood (<50 copies/ml) within one year of the time of infection as part of the Acute Infection and Early Disease Research Project (AIEDRP). The study design contains two treatment cycles, in each of which HAART will be stopped for up to 12 weeks and the viral set point that is achieved will be measured. Each study participant will receive IL2 during one of the treatment cycles. If the hypothesis is true, viral set points in a given treatment cycle should be lower in those who received IL2 in that cycle than in those who did not. We further hypothesize that the extent of HIV suppression of HIV will correlate with the magnitude of the CD4+ and CD8+ T cell responses to recurrent viremia. To test this hypothesis, short-term lymphocyte cultures will be stimulated with HIV peptides that span all HIV genes and the proportion of cells that are activated will be measured by flow cytometry using CD69 and intracellular production of interferon-,{ as indicators of cellular activation. The data obtained will help determine if early treatment of HIV is clinically beneficial, and whether direct measurement of HIV-reactive cells can predict the ability of the host immune response to control HIV replication. The revision addresses all points in the critique of the original application, in particular distinguishing the proposed research from previous research in the use of lL2 to treat early HIV infection. PERFORMANCE SITE ========================================Section End===========================================