Essential Fatty Acid Deficiency as a modifiable determinant of cognitive dysfunction among 6-18-year-old Ugandan children of varying perinatal HIV status

点击翻译按钮获取中文摘要

PROJECT SUMMARY/ABSTRACT More than 1 in 3 children from low middle-income countries are at risk of neurocognitive disorder (ND) and/or significant scholastic problems due to high burden of infectious morbidity and malnutrition which contributes to immune dysfunction and disruption of normal host-microbe interactions in the gut (i.e., intestinal dysbiosis). While all children are at risk, the risk of neurocognitive dysfunction for perinatally HIV-infected (PHIV) and HIV-exposed uninfected (HEU) children is amplified by current and/or early life antiretroviral therapy (ART). ART for HIV-infected pregnant women effectively reduces the likelihood of mother-to-child transmission of HIV. This exposure, however, increases the likelihood of a range of risk factors for adverse neurodevelopmental outcomes such as low birth weight, metabolic problems, and neurotoxicity among children whose mothers received ART in pregnancy. Further, persons living with HIV and HEU children have different intestinal microbiomes compared to community controls. The extent to which interactions between nutritional deficiency, intestinal dysbiosis, and current ART or in utero/peripartum ART history among HIV-affected children creates a negative feedback loop that worsens ND, related outcomes relative to HIV unexposed uninfected (HUU) children is unknown. This gap in current understanding is addressed in this project. As part of completed and ongoing research, our team has established and maintained a large cohort of school-aged and adolescent (ages 6 to 18 years) PHIV (n=255), HEU (n=254) and HUU (n=257) children from Uganda. Most (49.7%) HIV exposed children in our existing cohort did not receive any peripartum ART to prevent HIV mother-to-child-transmission. The vast majority of those that received any peripartum intervention were exposed to sub-optimal IPA (34.8%) and a relative minority (15%) were exposed to combination ART through their mothers in the in utero/peripartum period. The parent project allows this team to follow the already established cohort for three more years, conduct annual assessment of cognition and repeated measures of nutrition, intestinal dysbiosis, and immune dysfunction. The data will be integrated with already available information to implement definitive analyses of relationships between change in neurocognitive outcomes over 36 months follow-up and perinatal HIV status, early ART status, and Essential Fatty Acid Deficiency. Overall Impact: By implementing this project, we will identify children who are at risk of worse developmental outcomes so that the available supportive care interventions can be directed to those in greatest need. Second, the predictors of neurocognitive risk evaluated are potentially modifiable, opening another avenue to intervene to ensure that all children are developmentally thriving in the long-term.