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)
Mina Shah1, Caroline Kabwe2, Maria Molinaro3, Allyson Metro4, Esau Mbewe2, Pelekelo Kabundula2, Milimo Mweemba2, Sylvia Mwanza-Kabaghe2, Heather Adams5, Gretchen Birbeck6, David Bearden1
1University of Rochester School of Medicine, 2University of Zambia, 3Johns Hopkins University School of Medicine, 4Vanderbilt University Medical Center, 5University of Rochester, 6University of Rochester/CHET
Objective:

1. Examine differences in monocyte populations and activated platelet-monocyte complexes between HIV-infected and HIV-exposed uninfected (HEU) populations

2. Determine whether soluble biomarkers (including IL-6, sCD163, sCD14, CRP, TNFα, TNFR1, and TNFR2) are associated with cognitive function at baseline

3. Determine whether soluble biomarkers are associated with neurocognitive changes over time

Background:

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.

Design/Methods:
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.
Results:

Biomarkers sCD163, sCD14, CRP, and TNFα were significantly higher in concentration (p < 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 < 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 < 0.05) in neurocognitively impaired participants.

Conclusions:

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.

10.1212/WNL.0000000000202219