Accelerated CD8⁺ T cell maturation in infants with perinatal HIV infection

In perinatal HIV infection, early antiretroviral therapy (ART) initiation is recommended but questions remain regarding infant immune responses to HIV and its impact on immune development. Using single cell transcriptional and phenotypic analysis we evaluated the T cell compartment at pre-ART initiation of infants with perinatally acquired HIV from Maputo, Mozambique (Towards AIDS Remission Approaches cohort). CD8⁺ T cell maturation subsets exhibited altered distribution in HIV exposed infected (HEI) infants relative to HIV exposed uninfected infants with reduced naive, increased effectors, higher frequencies of activated T cells, and lower frequencies of cells with markers of self-renewal. Additionally, a cluster of CD8⁺ T cells identified in HEI displayed gene profiles consistent with cytotoxic T lymphocytes and showed evidence for hyper expansion. Longitudinal phenotypic analysis revealed accelerated maturation of CD8⁺ T cells was maintained in HEI despite viral control. The results point to an HIV-directed immune response that is likely to influence reservoir establishment.