CD8+ cells and small viral reservoirs facilitate post-ART SIV control in MHC-M3+ Mauritian cynomolgus macaques

Sustainable HIV remission after antiretroviral therapy (ART) withdrawal, or post-treatment control (PTC), remains a top priority in the HIV field. We observed surprising PTC in an MHC-haplomatched cohort of SIVmac239+ Mauritian cynomolgus macaques (MCMs) initiated on ART at two weeks post-infection (wpi). For six months after ART withdrawal, we observed undetectable or transient viremia in seven of eight MCMs. In vivo CD8a depletion induced rebound in all animals, indicating the PTC was mediated by CD8a+ cells. We found that MCMs had a smaller acute viral reservoir than a cohort of identically infected rhesus macaques, a population that rarely develops PTC. The mechanisms by which unusually small viral reservoirs and CD8a+ cell-mediated virus suppression enable PTC can be investigated using this model of PTC in MHC-haplomatched MCMs. If the immunological mechanisms that can engender PTC are defined, this model could designate therapeutic targets for HIV remission strategies in humans. Overall design: Comparative gene expression proifiling analysis of RNA-seq data for CD8+ T cells isolated from peripheral blood mononuclear cells (PBMCs) of SIV+ Mauritian Cynomolgus macaques.