Impact of HIV and toxic metals exposure on neurodevelopment at school age

About This Grant

ABSTRACT There are over 16 million children exposed to HIV (CHEU), the majority of whom reside in East and Southern Africa (ESA). This population is expected to grow as more women living with HIV access services to prevent vertical transmission of HIV. Evidence points to poorer neurodevelopment outcomes among CHEU compared to HIV unexposed children (CHU). Exposure to neurotoxic metals and pesticides also play a role in pathogenesis and may synergistically affect neurocognitive outcomes among CHEU. Studies that determine the combined impact of HIV and environmental exposures on child outcomes are lacking, despite the high prevalence of these exposures in ESA. Understanding whether HIV exposure impacts school-age outcomes has been challenged by changing ART regimens as the epidemic has evolved, and lack of assessment of multiple risk factors including environmental exposures. We propose to extend follow-up for a well characterized large cohort (n=2,000) of CHEU/CHU, enrolled at age 6 weeks and followed up to 3 years, to study neurodevelopmental outcomes at school age (age 5-8) and the impact of HIV and environmental exposures on neurodevelopmental outcomes. We will use exposure, biological samples, and neurodevelopmental data available from the first 3 years of life. The majority of CHEU were exposed to maternal dolutegravir-based ART (77%) and 85% started ART pre-conception. In Aim 1, using stored samples and neurodevelopmental data collected in the first 3 years of life, we will test for Pb levels and determine the association between early Pb exposure and neurodevelopment and determine whether HIV modified the impact of Pb exposure. In Aim 2, we will re-enroll 1,000 children and follow them up to age 8 years to determine the longer-term impact of HIV and Pb exposure on neurocognition and motor function. In Aim 3, we will assess concentrations of neurotoxic heavy metal exposures and pesticides using novel biological samples (nails and hair). Pb and heavy metal assays will be conducted using x-ray fluorescence (XRF) and we will assess associations between these exposures, HIV exposure, and neurocognition. This proposal leverages a large unique longitudinal mother-child cohort of CHEU and CHU, with comprehensive neurodevelopmental assessments and analysis at scale, to comprehensively understand burden, mechanism and neurodevelopmental outcomes in CHEU. We will utilize novel biological samples and efficient technology to assess environmental exposures contributing evidence on inform use of these methods to assess environmental exposures in ESA and globally. We will work with national and global health leaders, community members, and policymakers to discuss study findings, implications, and next steps.