Plasma Biomarkers as Indicators for Neurocognitive Impairment in HIV+ Individuals
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Purpose: Chronic inflammation in HIV patients correlates with the severity of HIV-associated neurocognitive disorders (HAND), suggesting that inflammatory mediators could be indicators for the progression of HIV-associated neurocognitive impairment. The current clinical evaluations for HAND are designed for diagnosis after the onset of the disorder, limiting avenues for intervention. Therefore, there is a need for prognostic biomarkers to determine the likelihood for HAND development. This study aims to identify inflammatory factors from blood plasma and peripheral blood mononuclear cell (PBMC) that correlate with neurocognitive performance to serve as prognostic markers of HIV-associated neurocognitive impairment. We hypothesize that these associations are dependent upon race and sex. Methods: A total of 121 HIV+ male and female African, Caucasian and Hispanic Americans were enrolled for two separate study visits. At each visit, participants underwent a drug screen, a blood draw and a computerized neurocognitive assessment in memory, psychomotor speed, reaction time, complex attention, cognitive flexibility, processing speed and executive function using the CNS Vital Signs software. Participant blood was processed to isolate plasma and in vivo PBMCs, PBMCs were further incubated in media for 24 hours. A panel of inflammatory factors were measured in the participant samples by ELISA and real-time PCR. A multivariate multiple linear regression model was utilized to identify inflammatory factors that significantly associate with neurocognitive scores. Results: Higher plasma levels of monocyte chemoattractant protein 2 or tissue inhibitor of metalloproteinases 1 significantly associated with lower neurocognitive scores in all domains tested except reaction time. In addition, higher plasma levels of chemokine c-c ligand 17, interleukin (IL) 10, and IL-23 significantly associated with lower neurocognitive scores in processing speed and executive functioning. Conclusion: Identified plasma markers of neurocognitive performance can be utilized as indicators of neurocognitive impairment in HIV patients. This suggests that the markers can predict neurocognitive decline at the second study visit. This study may provide an avenue for early therapeutic intervention.