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

Abstract Post-treatment HIV controllers (PTCs) offer evidence that HIV remission can be achieved in some people after antiretroviral treatment (ART) discontinuation. However, the circumstances and mechanisms leading to PTC remain unclear. We evaluated the impact of early (week 4) vs late (week 24 post infection) ART initiation in SIVmac251-infected cynomolgus macaques that received 2 years of ART before analytical interruption (ATI). Early ART strongly promoted PTC. The divergent outcome of early and late-treated macaques was not related to differences in the frequency of infected cells at ATI. Rather, early treatment favored the development of long-term memory CD8+ T cells with enhanced proliferative and SIV suppressive capacity that were able to mediate a robust secondary-like response upon viral rebound. Our model allowed to formally demonstrate a link between ART initiation during primary infection and the promotion of post-treatment control and provided results that may guide the development of new immunotherapies seeking-HIV remission.