Antiretroviral treatment alters relationship between MCP-1 and neurometabolites in HIV patients.
OBJECTIVE
The relationships between neurometabolites and macrophage chemoattractant protein (MCP-1) in serum and cerebrospinal fluid (CSF) were evaluated in HIV patients before and after antiretroviral treatment.


METHODS
Prior studies found higher CSF MCP-1 levels in patients with HIV-associated dementia compared to those in neuroasymptomatic. We hypothesized that CSF MCP-1 levels would correlate inversely to neuronal metabolites [including N-acetyl compounds, glutamate+glutamine, as assessed by principal component analyses (PCA)] and positively to glial metabolites (including myo-inositol and choline compounds).


METHODS
Thirty-nine antiretroviral-naive HIV patients were evaluated prospectively with proton magnetic resonance spectroscopy (1H MRS), and serum and CSF MCP-1 measurements prior to highly active antiretroviral therapy (HAART); 31 of these patients completed follow-up studies after 3 months of HAART but only 24 had follow-up CSF studies.


RESULTS
After HAART, brain metabolites and clinical signs showed no change despite improvements in systemic (CD4 counts, plasma viral load, MCP-1) and CSF (viral load and MCP-1) variables. CSF, but not serum, MCP-1 levels correlated inversely with the neuronal component (from PCA) prior to treatment (r=-0.59, P=0.0008). Conversely, after 3 months of HAART, the glial component (from PCA) correlated positively with CSF MCP-1 levels (r=0.70, P=0.0002; ANCOVA interaction for treatment status, P=0.003).


CONCLUSIONS
These findings suggest that higher CSF MCP-1 levels are associated with neuronal dysfunction in untreated patients. After 3 months of HAART, the decreased systemic factors (viral burden, systemically derived MCP-1) no longer associate with neuronal dysfunction, but subjects with the strongest glial response in the brain continue to produce the highest levels of MCP-1.
Chang
Linda
L
Department of Medicine, John A. Burns School of Medicine, University of Hawai, Honolulu, HI, USA. lchang@hawaii.edu
Ernst
Thomas
T
St Hillaire
Coryse
C
Conant
Katherine
K
D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D018791:CD4 Lymphocyte Count; D018932:Chemokine CCL2 / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D002794:Choline / Q000032:analysis; D003401:Creatine / Q000032:analysis; D005260:Female; D018698:Glutamic Acid / Q000032:analysis; D005973:Glutamine / Q000032:analysis; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007124:Immunoenzyme Techniques; D007294:Inositol / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011446:Prospective Studies; D019562:Viral Load
D019380:Anti-HIV Agents; D018932:Chemokine CCL2; D005973:Glutamine; D018698:Glutamic Acid; D007294:Inositol; D003401:Creatine; D002794:Choline