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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.

We characterized T cell phenotypes in 74 paired blood and cerebrospinal fluid (CSF) samples of HIV-infected and uninfected persons using four-color flow cytometry. CD4+ and CD8+ T cells subsets were further characterized by identifying activated/resting and memory/naive subsets in CSF and blood using the markers CD38/HLA-DR and CD45RA/CD62L, respectively. With and without HIV-infection, the proportion of CD4+ T cells and memory T cells among T cells in CSF was higher compared to blood. In HIV-infection, activated CD4+ and CD8+ T cells in CSF were more abundant than in uninfected controls. As expected, combination antiretroviral therapy (ART) reduced T cell activation in CSF and blood.

In HIV-1-infected subjects, the magnitude of HIV-1 viral load in cerebrospinal fluid (CSF) correlates with the CSF white cell count. To determine whether HIV-1-producing T cells appear in CSF and whether their percentage and number correlate with viral load in CSF, we developed a flow cytometric assay that detects HIV-1-producing T cells by identifying intracellular p24 HIV-1 antigen. We found that most CSF T cells were not HIV-1 producing, even when cell-free viral load in CSF was high. Most activated T cells in CSF were also not HIV-1 producing, but the activated CD38+ CD4 T-cell fraction in CSF was independently associated with the fraction of HIV-1-producing T cells in CSF. We conclude that HIV-1-producing T cells appear in CSF and that their percentage and number correlate with cell-free viral load in CSF, even though the CSF total white cell count remains the best predictor for CSF viral load. In HIV-1 infection, CSF white cell counts seem to contain a large number of uninfected cells. White cell counts and viral load in CSF may result from systemic inflammation and immune activation.