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Background:  HIV-1-infected monocyte-derived macrophages trafficking into the central nervous system are a risk factor for HIV-associated dementia (HAD). We hypothesized that individuals with chronic HIV-1 infection on HAART have a circulating macrophage-like monocyte phenotype that continue to feed HIV-1 into the brain.

Methods:  We performed global gene expression analyses (20,000 probes) on CD14⁺ monocytes isolated from HIV-1-infected individuals with high viral load (n = 6), low viral load (n = 8), and HIV-1 seronegative controls (n = 5). HIV-1-related changes in monocyte gene expression were confirmed by RT-PCR, immunohistochemistry and flow cytometry.

Results:  Monocytes from subjects with high viral load (n = 10) had a significantly higher (p < 0.001) expression of sialoadhesin (CD169) by flow cytometry than monocytes from individuals with low viral load (n = 16) or controls (n = 4). While a subset of monocytes expressed CD16, all CD14⁺ cells from high-viral-load subjects expressed sialoadhesin. Archived brain sections from individuals with HIV encephalitis showed perivascular sialoadhesin-positive macrophages (CD68) while brains from controls were negative.

Conclusions:  Circulating CD14⁺ monocytes from individuals with high viral load have an elevated macrophage marker of chronic inflammation. In rheumatoid arthritis and Kaposi’s sarcoma, expression of sialoadhesin has been restricted to macrophages localized at the site of chronic inflammation. We report that sialoadhesin is present on circulating monocytes from subjects with high viral load on HAART as well as perivascular brain macrophages in HIV-1 encephalitis. These results suggest that subjects with high viral load and other risk factors continue to be at risk for HIV-1 dementia.

Keywords: Monocyte; HIV-1; neuroinflammation