Etude de l’établissement des réservoirs VIH lors de la primo-infection et de l’impact des traitements antirétroviraux très précoces sur ces réservoirs

Abstract : HIV primary infection is a critical period in the establishment of the reservoirs that justifies the initiation of an early treatment. We started a randomised trial to assess the impact of a two-year intense HAART (ANRS147 OPTIPRIM trial: five-drug therapy versus. three-drug therapy) on the blood reservoir; within this this trial, we included some pathophysiological studies. Thus, we show that during the primary infection, viruses have a low genetic diversity in blood and rectal compartments. The reservoir establishes itself as early as the first month of the infection by spreading a homogeneous viral cluster in CD4 T cells subsets, naive T cells (TN), central memories (TCM), transitional memories (TTM), effector memories (TEM), and resting T cells. This results in a disruption of the lymphocyte homeostasis, linked to the low contribution to the reservoir of TN and TCM, which are little differentiated cells with long half-lives. Moreover, we show that, at the time of the primary infection, the majority of patients do not have the ability to develop CD8 T cells responses that could suppress the viral replication, as HIV Controllers patients do. After two years of treatment, we observe that there is no evolution of the viral diversity, but the size of the reservoir is significantly reduced. The abnormalities of the CD4 T cells lymphocyte homeostasis remain, but the very early treatment was able to protect the TN and TCM. The five-drug therapy does not have any additional benefit, but we confirm the idea that early treatment can induce long-term virological control after the discontinuation of the treatment. Our results show that a treatment lasting more than two years would be able to reinforce the reduction of the reservoir. These results should be taken into account in the development of future trials aiming to reduce the reservoir in patients treated at the time of primary infection for a sustainable remission.
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Antoine Chéret. Etude de l’établissement des réservoirs VIH lors de la primo-infection et de l’impact des traitements antirétroviraux très précoces sur ces réservoirs. Virologie. Université René Descartes - Paris V, 2014. Français. ⟨NNT : 2014PA05T013⟩. ⟨tel-01059807⟩

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