Plasma levels of soluble CD14 independently predict mortality in HIV infection

Netanya G. Sandler, Handan Wand, Annelys Roque, Matthew Law, Martha C. Nason, Daniel E. Nixon, Court Pedersen, Kiat Ruxrungtham, Sharon R. Lewin, Sean Emery, James D. Neaton, Jason M. Brenchley, Steven G. Deeks, Irini Sereti, Daniel C. Douek

Research output: Contribution to journalArticlepeer-review

684 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)780-790
Number of pages11
JournalJournal of Infectious Diseases
Volume203
Issue number6
DOIs
StatePublished - Mar 15 2011

Bibliographical note

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.

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