Plasma levels of soluble CD14 independently predict mortality in HIV infection

Sandler, Netanya G., Wand, Handan, Roque, Annelys, Law, Matthew, Nason, Martha C., Nixon, Daniel E., Pedersen, Court, Ruxrungtham, Kiat, Lewin, Sharon R., Emery, Sean, Neaton, James D., Brenchley, Jason M., Deeks, Steven G., Sereti, Irini and Douek, Daniel C. (2011) Plasma levels of soluble CD14 independently predict mortality in HIV infection. Journal of Infectious Diseases, 203 6: 780-790. doi:10.1093/infdis/jiq118

Author Sandler, Netanya G.
Wand, Handan
Roque, Annelys
Law, Matthew
Nason, Martha C.
Nixon, Daniel E.
Pedersen, Court
Ruxrungtham, Kiat
Lewin, Sharon R.
Emery, Sean
Neaton, James D.
Brenchley, Jason M.
Deeks, Steven G.
Sereti, Irini
Douek, Daniel C.
Title Plasma levels of soluble CD14 independently predict mortality in HIV infection
Journal name Journal of Infectious Diseases   Check publisher's open access policy
ISSN 0022-1899
Publication date 2011-03-01
Year available 2011
Sub-type Article (original research)
DOI 10.1093/infdis/jiq118
Open Access Status Not yet assessed
Volume 203
Issue 6
Start page 780
End page 790
Total pages 11
Place of publication Cary, NC, United States
Publisher Oxford University Press
Language eng
Formatted abstract
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.
Keyword Chronic human immunodeficiency virus (HIV)
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID AI-76174
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Child Health Research Centre Publications
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