Longitudinal maternal and early life (neuro)immune mechanisms underlying neurodevelopmental and behavioural impairments in HIV-exposed uninfected children in a South African birth cohort

While prevention of mother-to-child transmission (PMTCT) success has resulted in the decline in paediatric HIV infection, the number of HIV-exposed uninfected (HEU) infants has rapidly risen. In 2018, the population of HEU children in sub-Saharan Africa was estimated to be 13.2 million.

In utero exposure to HIV may exert detrimental influences on the intricate neurodevelopmental processes during the first five years of life, with long-lasting effects on cognitive performance and behaviour.

Our understanding of the pathophysiological mechanisms that are involved in conferring risk for neurodevelopmental deficits due to HIV exposure remains limited.

Altered neuroimmune regulation during pregnancy and early life may negatively affect neurodevelopment in children and in the context of maternal HIV infection may, in part, explain the delayed neurodevelopment observed in HEU children.

However, the temporal regulation of neuroimmune markers during the critical period of the developing brain in HEU children remains unexplored.

Importantly, it is also unknown at which stage (from in utero through to five years of age) the developing brain in children with HEU is affected.

This study proposes to investigate longitudinally the association between maternal and infant neuroimmune function and brain development and neurodevelopmental outcomes in South African HEU children.