Systemic Inflammation and Growth in Children Born to Mothers With and Without HIV in Rural Zimbabwe

Abstract

Background. Sixteen million children are HIV-exposed but uninfected (HEU) due to the prevention of vertical transmission. Despite avoiding HIV, children who are HEU face higher risks of infections and poorer growth and development than children HIV-unexposed (HU), though mechanisms remain unclear. We hypothesized that systemic and vascular inflammations contribute to disparities. Methods. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial recruited pregnant women at ∼12 gestational weeks between 2012 and 2015 in rural Zimbabwe (∼15% HIV prevalence, >80% antiretroviral therapy coverage). Plasma biomarkers were measured using enzyme-linked immunosorbent assay (ELISA) and multiplex assays in a subgroup of children at 1 month of age and compared using generalized estimating equations adjusted for trial arm, maternal age, birthweight, prematurity, sex, and age. Principal component analysis was used to reduce dimensionality of biomarkers. Results. Seventy-one children who are HEU and 62 who are HU were included. Twenty-two of 27 biomarkers were raised in HEU versus HU. Systemic inflammatory markers (IL-1β/interferon-γ/TNF-α/sCD14) and vascular activation markers (L-selectin/VCAM-1) were significantly higher. HIV-exposed but uninfected infants gained 6.1 g/day less than HU infants in the first month after birth. Although one principal component, primarily driven by vascular endothelial growth factor, was associated with increased growth rate, the difference between HEU and HU growth trajectories was not affected by differences in any principal components, suggesting that inflammation does not explain lower growth amongst HEU children. Conclusions. Children who are HEU have significantly elevated systemic and vascular inflammatory biomarkers compared with those who are HU. Understanding causes and consequences of this inflammatory imbalance may identify new intervention targets for improving outcomes in this vulnerable group.