Abstract
Despite the introduction of antiretroviral therapy (ART) in the prevention of mother to child transmission (PMTCT) of HIV, there is still vertical transmission of HIV with 1.5 million children living with HIV worldwide and approximately 130,000 new infections in 2022. HIV targets CD4 T cells and causes immune dysregulation which could be detrimental for the development of the immune system during early life. Early ART initiation has been shown to limit the viral reservoir size, disease progression and partially reduce immune activation, but there is still persistent immune activation, microbial translocation, and elevated exhausted immune cells during suppressive ART therapy. Understanding the interplay between HIV and the early life immune system could provide insight into the long-term effects of infection on these children and provide information on immune-based intervention strategies for early life.To investigate the effect of HIV infection of early life immune development and the infant anti-HIV response, a group of perinatally HIV exposed infected infants (HEI) enrolled at 1 to 2 months of age that initiated ART at enrollment and a group of age-matched perinatally HIV exposed uninfected infants (HEU) were enrolled and followed prospectively during the first 2 years of life. Utilizing multiparameter flow cytometry and single cell-RNA sequencing (scRNA-seq) approaches we investigated the development of both the innate and adaptive immune system and the effect of HIV infection. We observed altered distribution of major subsets in the T and NK cell compartment and elevated immune activation in T cells, NK cells, monocytes, and Dendritic cells (DC) at Pre-ART initiation in HEI compared to age-matched uninfected infants that was observed until 18 months in T cells. In addition, we identified by scRNA-seq a cluster of CD8 T cells with a gene profile consistent with CTLs in only HEI. This thesis provides insight into potential immune populations that are associated with viral replication, or control, that can be used as target for immune-based HIV cure strategies during early life.