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Quantifying and Predicting the Effect of Exogenous Interleukin-7 on CD4+T Cells in HIV-1 Infection

Abstract : Exogenous Interleukin-7 (IL-7), in supplement to antiretroviral therapy, leads to a substantial increase of all CD4+ T cell subsets in HIV-1 infected patients. However, the quantitative contribution of the several potential mechanisms of action of IL-7 is unknown. We have performed a mathematical analysis of repeated measurements of total and naive CD4+ T cells and their Ki67 expression from HIV-1 infected patients involved in three phase I/II studies (N = 53 patients). We show that, besides a transient increase of peripheral proliferation, IL-7 exerts additional effects that play a significant role in CD4+ T cell dynamics up to 52 weeks. A decrease of the loss rate of the total CD4+ T cell is the most probable explanation. If this effect could be maintained during repeated administration of IL-7, our simulation study shows that such a strategy may allow maintaining CD4+ T cell counts above 500 cells/µL with 4 cycles or fewer over a period of two years. This in-depth analysis of clinical data revealed the potential for IL-7 to achieve sustained CD4+ T cell restoration with limited IL-7 exposure in HIV-1 infected patients with immune failure despite antiretroviral therapy.
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Submitted on : Thursday, January 22, 2015 - 12:30:33 PM
Last modification on : Friday, November 18, 2022 - 9:26:43 AM

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Rodolphe Thiébaut, Julia Drylewicz, Mélanie Prague, Christine Lacabaratz, Stéphanie Beq, et al.. Quantifying and Predicting the Effect of Exogenous Interleukin-7 on CD4+T Cells in HIV-1 Infection. PLoS Computational Biology, 2014, 10 (5), pp.e1003630. ⟨10.1371/journal.pcbi.1003630⟩. ⟨hal-01108204⟩



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