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Background: Activated CD14⁺/CD16⁺ monocytes likely play a critical role in the pathogenesis of HIV-1-related brain disease and have been found in brains of HIV-1 infected subjects with and without clinical dementia. These monocytes/macrophages are located in the perivascular area of the brain and derive from blood-borne, bone marrow-derived precursors. It is unknown whether activated monocytes appear in cerebrospinal fluid (CSF) in HIV-infection, and how their presence is influenced by antiretroviral therapy.

Methods: We used 6-color flow cytometry and quantification beads to identify percentages and absolute counts of activated monocytes in paired blood and CSF samples in 83 HIV-infected and 8 uninfected subjects. The HIV-1-infected cohort was divided a priori into 3 groups: 26 treatment successes (HIV RNA<500 copies/ml), 25 treatment failures (HIV RNA>500 copies/mL) and 32 off treatment.

Results: In both HIV-infected and uninfected subjects, a large percentage of CD14+ monocytes in CSF expressed activation markers CD16 and CCR5 in contrast to blood where the majority of monocytes were not activated. We found that the mean percentage of activated CD16+ monocytes in CSF was highest in the treatment successes (47.0+20.3%: mean+SD) compared with those failing treatment (38.4+21.3) or off treatment (35.1+19.5; p = 0.036 comparing successes with untreated). All infected subjects had higher percentages of these cells than the uninfected controls (29.3+18.0). In contrast, the mean percentages of activated CD16⁺ monocytes in blood were lowest in the treatment successes (10.4+5.0), higher in treatment failures (11.2+7.5) and highest in subjects off treatment (13.9+5.4; p = 0.04 comparing successes with untreated) and uninfected controls (14.5+4.8). We found a similar CD14⁺/CD16⁺ monocyte distribution among groups in CSF and blood using absolute counts with the exception of blood CD14⁺/CD16⁺ counts/µL that, in uninfected subjects, were comparable to those off treatment, not higher.

Conclusions: Monocytes in CSF compared to blood tend to express activation markers in the absence and presence of HIV-1-infection. In subjects with controlled viral load (treatment "successes"), activated monocytes appeared enriched in CSF and lowered in blood compared to control subjects and those off treatment. This trafficking of monocytes to the CSF, and possibly CNS, may be an immune response to HIV-1 infection in brain tissue that persists despite ART.

Keywords: cerebrospinal fluid; monocytes; immune activation