Plasma levels of soluble CD14 independently predict mortality in HIV infection.
BACKGROUND
Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an independent predictor of HIV disease progression. The association of microbial translocation with clinical outcome remains unknown.


METHODS
This nested case-control study included 74 subjects who died, 120 of whom developed cardiovascular disease and 81 of whom developed AIDS during the Strategies for Management of Anti-Retroviral Therapy (SMART) study with matched control subjects. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), soluble CD14 (sCD14), endotoxin core antibody (EndoCAb), and 16S ribosomal DNA (rDNA) were measured in baseline plasma samples.


RESULTS
Subjects with the highest quartile of sCD14 levels had a 6-fold higher risk of death than did those in the lowest quartile (95% confidence interval, 2.2-16.1; P<.001), with minimal change after adjustment for inflammatory markers, CD4(+) T cell count, and HIV RNA level. No other marker was significantly associated with clinical outcomes. I-FABP, LPS, and sCD14 were increased and EndoCAb was decreased in study subjects, compared with healthy volunteers. sCD14 level correlated with levels of IL-6, C-reactive protein, serum amyloid A and D-dimer.


CONCLUSIONS
sCD14, a marker of monocyte response to LPS, is an independent predictor of mortality in HIV infection. Therapeutic attenuation of innate immune activation may improve survival in patients with HIV infection.
Human Immunology Section, Vaccine Research Center.
Netanya G
NG
Sandler
Handan
H
Wand
Annelys
A
Roque
Matthew
M
Law
Martha C
MC
Nason
Daniel E
DE
Nixon
Court
C
Pedersen
Kiat
K
Ruxrungtham
Sharon R
SR
Lewin
Sean
S
Emery
James D
JD
Neaton
Jason M
JM
Brenchley
Steven G
SG
Deeks
Irini
I
Sereti
Daniel C
DC
Douek
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes; D016022:Case-Control Studies; D002423:Cause of Death; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D015658:HIV Infections / Q000097:blood* / Q000401:mortality*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008070:Lipopolysaccharides / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D055815:Young Adult
D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012367:RNA, Viral
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