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

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.

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.

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.