Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells

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Passaes, Caroline | Desjardins, Delphine | Chapel, Anaïs | Monceaux, Valérie | Lemaitre, Julien | Mélard, Adeline | Perdomo-Celis, Federico | Planchais, Cyril | Gourvès, Maël | Dimant, Nastasia | David, Annie | Dereuddre-Bosquet, Nathalie | Barrail-Tran, Aurélie | Gouget, Hélène | Guillaume, Céline | Relouzat, Francis | Lambotte, Olivier | Guedj, Jérémie | Müller-Trutwin, Michaela | Mouquet, Hugo | Rouzioux, Christine | Avettand-Fenoël, Véronique | Le Grand, Roger | Sáez-Cirión, Asier

Edité par CCSD ; Nature Publishing Group -

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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