Neuroinflammatory Biomarkers and Cognitive Outcomes in HIV-Associated Neurocognitive Disorder Among Adults Receiving ART in Enugu State, South East Nigeria

HIV-associated neurocognitive disorder affects a substantial proportion of HIV-positive individuals on antiretroviral therapy and represents an underdiagnosed contributor to disability in Nigeria, with neuroinflammatory mechanisms incompletely characterised in West African populations. This research investigates neuroinflammatory biomarkers, their longitudinal trajectories, and their relationship with neurocognitive outcomes in adults with HAND at University of Nigeria Teaching Hospital, Enugu State, South East Nigeria. A prospective longitudinal design will recruit 180 ART-experienced HIV-positive adults stratified by neurocognitive status using the International HIV Dementia Scale and standard neuropsychological testing battery at baseline and 12-month follow-up. Cerebrospinal fluid and plasma samples will be analysed for neurofilament light chain, GFAP, chitinase-3-like protein 1, soluble CD163, beta-2-microglobulin, and cytokine profiles by multiplex ELISA and single-molecule array technology. Brain-derived neurotrophic factor, ART CNS penetration effectiveness scores, and CD4 trajectory data will be incorporated as modifiers. Machine learning-based biomarker panel construction will identify the combination with highest accuracy for HAND diagnosis and severity classification. Longitudinal biomarker trajectory modelling will characterise neuroinflammation dynamics in response to ART optimisation. Original contributions include the first longitudinal CSF neuroinflammatory biomarker study of HAND in a West African cohort, a novel HAND biomarker panel tailored to Nigerian population characteristics, and a theoretical extension of the neuroinflammatory model of HAND to include nutrition-immune interactions specific to sub-Saharan Africa. Findings will guide laboratory monitoring protocols and neuroprotective intervention strategies for HIV patients in South East Nigeria. Keywords: HAND, neuroinflammation, neurofilament light chain, HIV, antiretroviral therapy