Association between head circumference and monocyte phenotype in neonates exposed and unexposed to HIV at Kalafong Provincial Tertiary Hospital

Abstract

It is well documented that children living with human immunodeficiency virus (HIV) do not perform as well as children not living with HIV on general cognitive tests, processing speed, and visual-spatial tasks, and are at much higher risk for psychiatric and mental health issues. One would expect that HIV-exposed-uninfected (HEU) children would fare as well as HIV-unexposed-uninfected (HUU) children; however, research shows that HEU children have immune dysfunction, as well as higher morbidity and mortality than their HUU counterparts. There is also evidence that suggests that HEU children’s performance on certain neurodevelopmental tests is below that of HUU children by a small, but statistically significant, margin. This is cause for concern, since as many as 30% of children in some sub-Saharan countries, such as South Africa, are HEU. As these children enter school, they may be at risk of learning difficulties. The role of monocytes/macrophages in the development of the brain is a growing field of research. Macrophages in the brain, called microglia, assist in tissue remodelling, repair, and neurogenesis. An imbalance between macrophage phenotypes has been associated with various neurological diseases and inflammatory conditions, since classically activated microglia and/or macrophages are known to exert cytotoxic effects on neurons and oligodendrocytes. Macrophages of different activation profiles are linked to monocyte polarization in blood. This study therefore set out to characterise and compare the monocyte phenotypes of HEU and HUU children in blood and investigated the association between HIV exposure, neurological development as measured by head circumference (HC), and patterns of monocyte polarisation. For this study, 23 mothers living with and 19 mothers not living with HIV and their infants were randomly selected. At birth, the weight, height, and HC of the groups were similar, as were the z-scores for weight-for-length (WLZ), length-for-age (LAZ), weight-for-age (WAZ), body mass index (BMI) for-age (BAZ), and HC-for-age (HCZ). At the 10 week timepoint, HUU infants had a higher BMI, WLZ, and BAZ than HEU infants, and they were still heavier at the six months follow-up visit, as measured by WLZ. Lastly, at the 12 month follow-up visit, the BMI, WLZ, and BAZ were significantly higher, while LAZ was lower, in the HUU group. With regards to the monocyte subsets, HEU infants had a significantly higher proportion of intermediate monocyte (IM) at birth. No other statistically significant differences were seen with regards to the other monocyte phenotype subgroups or at any of the other time points. No correlation was found between monocyte polarisation and HC. This study therefore did not show that HIV-exposure affected the HC in this small group of infants. This finding bodes well for other HEU infants in similar circumstances. In future studies, more precise measurements for anthropometric data might reflect different results and the connection of cytomegalovirus (CMV) with HIV-exposure could be looked at for an enhanced understanding of HEU infants’ neurodevelopment.