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Effects Of Interleukin-2 Therapy Combined With Highly Active Antiretroviral Therapy On Immune Restoration In HIV-1 Infection: A Randomized Controlled Trial

Y. Lévy, C. Durier, R. Krzysiek, C. Rabian, C. Capitant, A. Lascaux, C. Michon, E. Oksenhendler, L. Weiss, J. Gastaut, C. Goujard, C. Rouzioux, J. Maral, J. Delfraissy, D. Émilie, J. Aboulker
Published 2003 · Medicine

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Background: Intermittent interleukin-2 (IL-2) therapy leads to a sustained increase of CD4 T cells in HIV-1-infected patients. Methods: Symptom-free HIV-1-infected patients who were naive to all antiretroviral drugs (n = 68) and/or to protease inhibitors (n = 50) and had a CD4 cell count of 200–550 × 106 cells/l were randomly assigned to start lamivudine/stavudine/indinavir alone (controls) or combined from week 4 with subcutaneous IL-2 (5 × 106 IU twice daily for 5 days: every 4 weeks for three cycles, then every 8 weeks for seven cycles). Immunological and virological results were monitored until week 74. Results: CD4 T cell counts increased more in the IL-2 group than in the controls (median increases 865 and 262 × 106 cells/l, respectively; P < 0.0001); an 80% increase in CD4 T cells was achieving by 89% of the IL-2 group and by 47% of the controls (P < 0.0001). Decrease of plasma viral loads was similar in both groups. Compared with controls, IL-2 induced a greater increase of naive and memory CD4 T cells, lymphocyte expression of CD28 and CD25 (P < 0.0001) and natural killer cells (P < 0.001). In a logistic regression analysis, odds of being responders to recall antigens in vitro was 8.5-fold higher in IL-2 recipients (P = 0.002) than in controls. The former experienced a higher level of antibody response to tetanus vaccination at week 64 than controls (32 and 8 haemagglutinating units/ml, respectively; P = 0.01). Conclusions: The combination of antiviral drugs and IL-2 induced a greater expansion and function of CD4 T cells than antiretroviral drugs alone.
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