We recently found that a new pathogenic chimeric simian-human immunodeficiency virus (SHIV) elicited heterologous human immunodeficiency virus type-1 (HIV-1) neutralizing antibodies (nAbs) in therapy-naïve young rhesus macaques (RMs) following neonatal SHIV infection. Moreover, a subset of the SHIV-infected young RMs spontaneously controlled viremia. Here we evaluated humoral and cellular immunity and plasma biomarkers associated with spontaneous viremia suppression in a new model of young SHIV-infected RMs that generated heterologous HIV-1 nAbs independent of viremia control to gain insights into pediatric immunity that may be harnessed by appropriate therapies in HIV-1-infected infants and children. We determined the levels of 31 plasma analytes (cytokines, chemokines, and growth factors) in SHIV-infected RMs over the course of infection and found that six analytes with chemoattractant or pro-inflammatory activities had significantly lower levels in plasma of RMs that controlled viremia compared to non-controllers. Single-cell transcriptomics of blood-derived immune cells demonstrated that RMs with viremia control had upregulated genes associated with immune activation and cytotoxic functions, whereas non-controllers had upregulated genes associated with immune cell exhaustion and dysfunction. In addition to CD8 T and natural killer cells, monocytes with upregulation of inhibitory genes previously reported only in cytotoxic cells constituted the immunologic environment associated with viremia suppression. These data implicated a complex immunologic milieu of viremia suppression that is not fully defined in pediatric subjects. Understanding immune cell subsets that may be harnessed to control viremia will provide insights into future designs of HIV-1 therapeutic strategies. [ABSTRACT FROM AUTHOR]