Contributors: Réservoirs viraux et contrôle immunitaire / Viral reservoirs and immune control; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); HIV, Inflammation et persistance - HIV, Inflammation and Persistence; Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; Institut Cochin (IC UM3 (UMR 8104 / U1016)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Immunologie humorale - Humoral Immunology; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord; Hôpital Necker - Enfants Malades AP-HP; The pVISCONTI study was funded by MSDAvenir, through a research grant to the ANRS-RHIVIERA consortium, and the ANRS; ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011)
نبذة مختصرة : International audience ; Abstract HIV remission can be achieved in some people, called post-treatment HIV controllers, after antiretroviral treatment discontinuation. Treatment initiation close to the time of infection was suggested to favor post-treatment control, but the circumstances and mechanisms leading to this outcome remain unclear. Here we evaluate the impact of early (week 4) vs. late (week 24 post-infection) treatment initiation in SIVmac 251 -infected male cynomolgus macaques receiving 2 years of therapy before analytical treatment interruption. We show that early treatment strongly promotes post-treatment control, which is not related to a lower frequency of infected cells at treatment interruption. Rather, early treatment favors the development of long-term memory CD8 + T cells with enhanced proliferative and SIV suppressive capacity that are able to mediate a robust secondary-like response upon viral rebound. Our model allows us to formally demonstrate a link between treatment initiation during primary infection and the promotion of post-treatment control and provides results that may guide the development of new immunotherapies for HIV remission.
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