Inflammatory and Immunologic Biomarkers Associated with Cognitive Impairment in Pediatric and Adolescent Patients with HIV in Lusaka, Zambia: A Sub-Study of the HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) (P4-8.005)

Abstract

<h3>Objective:</h3> Examine differences in monocyte populations and activated platelet-monocyte complexes between HIV-infected and HIV-exposed uninfected (HEU) populations Determine whether soluble biomarkers (including IL-6, sCD163, sCD14, CRP, TNFα, TNFR1, and TNFR2) are associated with cognitive function at baseline Determine whether soluble biomarkers are associated with neurocognitive changes over time <h3>Background:</h3> In 2018, 66,000 children in Zambia under 15 were HIV-positive. HIV is associated with neurocognitive impairment, and current antiretroviral therapy is not protective against some neurological impacts of chronic HIV infection, likely due to CNS inflammation. Though biomarkers conferring risk for neurocognitive impairment are unknown, biomarkers that have implications in monocyte activation and inflammatory response are strong candidates for investigation. Non-classical monocytes and activated platelet-monocyte complexes also play a role in chronic inflammation in the context of HIV, making them strong investigatory candidates, too. <h3>Design/Methods:</h3> This is a sub-study of the HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) longitudinal prospective study, through which blood is collected annually. Soluble biomarker quantities were measured by Ella Multiplex Cytokine Analyzer. Classical, intermediate, and non-classical monocyte populations, and platelet-monocyte complexes were determined with flow cytometry. Cognitive function was assessed via a comprehensive neuropsychological testing battery and represented by NPZ8 scores. <h3>Results:</h3> Biomarkers sCD163, sCD14, CRP, and TNFα were significantly higher in concentration (p &lt; 0.05) in the HIV-infected cohort than in the HEU cohort. In contrast, TNF-R1, TNF-R2, and IL-6 were significantly higher in concentration (p &lt; 0.05) in the HEU cohort. When stratified by cognitive performance within cohorts, sCD163, CRP, TNF-R1, TNF-R2, and IL-6 were all found in significantly greater concentration (p &lt; 0.05) in neurocognitively impaired participants. <h3>Conclusions:</h3> Perinatally-acquired HIV is associated with increased levels of several inflammatory serum biomarkers, and biomarker profile characterized by high levels of inflammation and immune activation is associated with poorer cognitive outcomes in HIV-infected youth. <b>Disclosure:</b> Ms. Shah has nothing to disclose. Miss Kabwe has nothing to disclose. Ms. Molinaro has nothing to disclose. Dr. Metro has nothing to disclose. Esau G. Mbewe has received research support from Research was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number K23NS117310. . Pelekelo Kabundula has nothing to disclose. Milimo Mweemba has nothing to disclose. Sylvia Mwanza-Kabaghe has nothing to disclose. The institution of Heather Adams has received research support from Current: NIH; Past: Abeona; Batten Research Alliance; American University Centers on Disabilities. An immediate family member of Heather Adams has received publishing royalties from a publication relating to health care. Heather Adams has received personal compensation in the range of $500-$4,999 for serving as a Consultant with Critical Path Institute. An immediate family member of Dr. Birbeck has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various. Dr. Birbeck has a non-compensated relationship as a Ambassador for Zambia with RSTMH that is relevant to AAN interests or activities. Dr. Bearden has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bearden has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis. Dr. Bearden has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for law firms.