TY - JOUR
T1 - Plasma levels of soluble CD14 independently predict mortality in HIV infection
AU - Sandler, Netanya G.
AU - Wand, Handan
AU - Roque, Annelys
AU - Law, Matthew
AU - Nason, Martha C.
AU - Nixon, Daniel E.
AU - Pedersen, Court
AU - Ruxrungtham, Kiat
AU - Lewin, Sharon R.
AU - Emery, Sean
AU - Neaton, James D.
AU - Brenchley, Jason M.
AU - Deeks, Steven G.
AU - Sereti, Irini
AU - Douek, Daniel C.
N1 - Funding Information:
This work was supported in part by the intramural program of the National Institute of Allergy and Infectious Disease, National Institutes of Health and NIH grant AI-76174. K.R. is partially supported by the Research-Team Strengthening Grant, the National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand.
PY - 2011/3/15
Y1 - 2011/3/15
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/jiq118
DO - 10.1093/infdis/jiq118
M3 - Article
C2 - 21252259
AN - SCOPUS:79952335046
SN - 0022-1899
VL - 203
SP - 780
EP - 790
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -
