Biomarkers of neurological status in HIV infection: A 3-year study

Purpose: To evaluate circulating cytokines and chemokines as correlates of the degree of brain injury in individuals with advanced human immunodeficiency virus (HIV) infection. Experimental design: Study participants included ten well-characterized subjects in advanced stage HIV infection. High-throughput multiplexed analysis was used to quantify markers of interest at baseline and 3 years later in the clinical course. Objective measurements of the brain were derived in vivo with quantitative magnetic resonance segmentation algorithms and with diffusion tensor imaging. Results: Of the markers examined, monocyte chemoattractant protein-1 (MCP-1 or CCL-2) was the most prominent correlate of brain injury. Elevated MCP-1 levels correlated with brain white matter alterations at the initial assessment. The relationship to injury was more extensive 3 years later; elevated MCP-1 was significantly correlated with measures of brain microstructural alterations and of abject atrophy. Conclusions and clinical relevance: The findings build on our prior observations that elevated MCP-1 levels may be a useful predictive marker for HIV-associated neurocognitive disorder. As a potent chemoattractant, MCP-1 may mediate injury through participation in self-reinforcing cycles of chronic immune activation and cytokine/chemokine-mediated neurotoxicity.