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Étude de la réponse immunitaire au traitement antirétroviral au cours de l'infection par le virus de l'immunodéficience humaine

Julien Saison 1
1 Pathogénie des Staphylocoques – Staphylococcal Pathogenesis
CIRI - Centre International de Recherche en Infectiologie - UMR
Abstract : More than 30 years after the discovery of HIV, between 20 and 30% of patients on highly active antiretroviral therapy (ART) do not recover normal levels of CD4 T lymphocytes (CD4). This immunological non response (INR) to ART is associated with an increased morbidity and mortality. There are many conflicting results in the literature related the role of T cells immune activation of T regulator cells (Treg), in INR. In order to clarify the links between INR, immune activation and Treg, we made two hypotheses: (i) there is a link between Treg’s percentage, immune activation of CD4 and / or CD8, and INR; and (ii) the percentage of Treg measured at ART introduction can be used as an independent predictor for INR. To test our hypotheses, we initially improved the immunophenotyping of Treg in daily practice, by comparing different Treg’s phenotype, and by validating in clinical samples a new « one step» staining method of intracellular FoxP3. Then we analyzed in a crosssectionnal study the links between INR, immune activation, different Treg’s subpopulations and detection of very low level viremia, in a population of HIV-1 infected patients, under suppressive ART for many years. Predictive factors associated with the INR were analyzed using multivariate analysis. Simultaneously, we performed a prospective study to analyse the prognostic role of Treg’s percentage at ART introduction on the CD4 reconstitution within 2 years. We have shown that INR after 7 years of ART was independently associated with CD4 nadir and Treg’s percentage. We found in INR patients a significant increase of CD4 immune activation, but not of CD8. Finally, we showed that the Treg’s percentage and the CD4 nadir were independant predictors of INR within 2 years from the start of ART. The effect of Treg at baseline on CD4 evolution was as lower as the CD4 nadir was higher. Measuring the percentage of Treg at ART introduction could be a simple and easy tool to use in daily routine. It could help to better target patients at risk of INR in association with the measurement of CD4 nadir. A follow-up of the cohort will confirm these results in the long term. Further studies will be conducted, focusing on patients with a low CD4 nadir, and on older patients, in order to explore the interactions between immunosenescence, immune activation and Treg
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Julien Saison. Étude de la réponse immunitaire au traitement antirétroviral au cours de l'infection par le virus de l'immunodéficience humaine. Microbiologie et Parasitologie. Université Claude Bernard - Lyon I, 2015. Français. ⟨NNT : 2015LYO10108⟩. ⟨tel-01661456⟩

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