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Background:  Monocyte chemoattractant protein (MCP)-1 is a chemokine that is particularly important in HIV neuropathogenesis, in part because it mediates macrophage migration into the brain. To date, dynamic changes in MCP-1 expression and HIV replication over time have been studied in cell culture and animal models, but not in humans. The objective of this study was to identify the relationships between MCP-1 and HIV following a change in antiretroviral therapy (ART). 

Methods: This was a prospective, observational study of changes in MCP-1 and HIV RNA in serial samples of plasma and CSF.  At least 1 pair of plasma-CSF samples was collected prior to ART interruption or initiation. Additional pairs were collected at intervals over the next 90 days . Nine men with HIV infection were followed during 13 treatment periods (6 ART interruptions and 7 initiations). MCP-1 levels were quantified in plasma and CSF by ELISA. HIV RNA levels were quantified by RT-PCR. 

Results: Following ART interruption, HIV RNA rebound in plasma preceded rebound in CSF in most subjects. While plasma and CSF HIV RNA levels remained elevated, MCP-1 levels peaked and then returned to baseline. In CSF, peak levels of MCP-1 and HIV RNA typically coincided. In plasma, MCP-1 levels increased only slightly, together with the increase in CSF MCP-1. The median fold-increase in plasma MCP-1 was 2, whereas for CSF it was 3. Following ART initiation, MCP-1 levels in CSF and plasma peaked after 1-2 days, with a median fold-increase of 1.3.

Conclusions:  MCP-1 levels were higher in CSF than plasma at all time points, indicating intrathecal production. Following ART interruption, peak changes in MCP-1 in plasma and CSF occurred concurrently, perhaps in response to, or as a trigger for, rebounding CSF viral load.  However, MCP-1 levels also peaked slightly after ART initiation, while viral load was declining, suggesting that MCP-1 is responsive to both increases and decreases in viral load.

Keywords: MCP-1; cerebrospinal fluid; HIV