Signature immune activation markers of growth and infectious morbidity in HEU children
Stephanie Shiau, PhD, MPH
BACKGROUND: HIV-exposed, uninfected (HEU) children are exposed to the effects of both maternal HIV infection and ART and have higher rates of morbidity and mortality than their HIV-unexposed peers. The mechanisms responsible for poorer infant health in HEU children of women with perinatally-acquired HIV (PHIV) are likely to be multifactorial but begin with the in utero environment, a critical period during which fetal programming occurs which impacts the long-term health of these HEU children.
GAP: Few studies have examined the influence of maternal inflammatory mechanisms on infant and child health outcomes in humans, particularly in HEU infants.
HYPOTHESIS: Our central hypothesis is that chronic inflammation and immune activation in pregnant women with PHIV due to lifelong HIV and ART contributes to poor in utero and postnatal growth as well as infectious morbidity in HEU children.
METHODS: This retrospective cohort study will measure immune activation markers in repository specimens from the second trimester of pregnancy in a well-characterized cohort of pregnant women – those with PHIV, those with non-perinatally acquired HIV (NPHIV) and those HIV-uninfected – and associate these markers with growth outcomes and infectious morbidity in HEU children.
IMPACT: Our findings will inform potential targets for intervention in pregnant women living with HIV (WLHIV), and future research directed towards treatment of ongoing inflammation in WLHIV and their infants may result in better health outcomes for millions of HEU infants, particularly those born to women with PHIV. Insights from this study may also have implications for other groups of children exposed to maternal inflammation in utero, including those born to obese mothers.