Post-treatment SIV control is associated with specific features of viral persistence before and after treatment interruption

Mechanisms underlying durable control of HIV after antiretroviral therapy interruption remain poorly understood. Here we provide a comprehensive longitudinal analysis in a non-human primate model of post-treatment control using SIVmac251-infected male cynomolgus macaques (pVISCONTI study). Controllers exhibit lower levels of SIV DNA, intact proviruses, transcriptional activity, and viral evolution compared to non-controllers in blood and tissues long after therapy interruption. Before interruption, controllers already have fewer intact proviruses in lymph nodes, and this difference persists in blood shortly after interruption, prior to viral rebound. Intact provirus levels in lymph nodes before interruption negatively correlate with CD8⁺ T-cell capacity to suppress SIV and reflect rebound magnitude. The study demonstrates that markers of post-treatment control are detectable in lymph nodes before therapy interruption and in blood shortly after, and suggests that host immune responses may shape intact provirus profiles during treatment. Using a non-human primate model, the authors show that SIV post-treatment control is associated with fewer intact proviruses in lymph nodes before treatment interruption, linked to stronger SIV-suppressive activity of CD8 T cells.