Enrichment of activated monocytes in cerebrospinal fluid during antiretroviral therapy.

ABSTRACT

OBJECTIVES: In HIV infection, activated monocytes are enriched in blood and in the perivascular area of the brain, especially in patients with HIV-associated dementia. Although clinical brain disease is uncommon during combination antiretroviral therapy (ART), autopsy series indicate that HIV-infected brain tissue can contain high numbers of monocytes/macrophages despite ART. DESIGN: We assessed activated monocytes in blood and cerebrospinal fluid (CSF) in 76 living patients on and off ART. Plasma lipids were measured because they have been associated with monocyte activation and ART. METHODS: A novel quantitative six-color flow cytometric approach was used to identify monocytes in blood and CSF and to evaluate monocyte activation status. RESULTS: The mean percentage and number of activated CD16 monocytes in CSF was highest in individuals on combination ART, especially in those receiving protease inhibitors (PI). CSF viral load was also associated with higher monocyte activation in CSF. The mean calculated low density lipoprotein (LDL)-, oxidized LDL- and total cholesterol in plasma were highest in patients receiving PI. CONCLUSIONS: Activated monocytes are enriched in the CSF of persons living with HIV-1 and receiving ART. This finding is consistent with previously reported autopsy series. The mechanisms and long-term clinical consequences of persistent monocyte activation require further study.