Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 203, Issue 6, Pages 780-790Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiq118
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Funding
- National Institute of Allergy and Infectious Disease, National Institutes of Health
- NIH [AI-76174]
- National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand
- MRC [MC_U122886352] Funding Source: UKRI
- Medical Research Council [MC_U122886352] Funding Source: researchfish
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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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