Enrichment of activated monocytes in cerebrospinal fluid during antiretroviral therapy.
OBJECTIVE
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.


METHODS
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.
Neuenburg
Jutta K
JK
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158, USA. jneuenburg@gladstone.ucsf.edu
Furlan
Scott
S
Bacchetti
Peter
P
Price
Richard W
RW
Grant
Robert M
RM
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002784:Cholesterol / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007958:Leukocyte Count; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D015999:Multivariate Analysis; D019713:Receptors, CCR5 / Q000378:metabolism; D019562:Viral Load
D019380:Anti-HIV Agents; D008055:Lipids; D019713:Receptors, CCR5; D002784:Cholesterol