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 journalArticle

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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
Externally publishedYes

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Virus Diseases
HIV
Mortality
Lipopolysaccharides
Fatty Acid-Binding Proteins
Serum Amyloid A Protein
Antibodies
CD4 Lymphocyte Count
Ribosomal DNA
C-Reactive Protein
Disease Progression
Case-Control Studies
Monocytes
Permeability
Interleukin-6
Healthy Volunteers
Acquired Immunodeficiency Syndrome
Cardiovascular Diseases
RNA
Confidence Intervals

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Sandler, N. G., Wand, H., Roque, A., Law, M., Nason, M. C., Nixon, D. E., ... Douek, D. C. (2011). Plasma levels of soluble CD14 independently predict mortality in HIV infection. Journal of Infectious Diseases, 203(6), 780-790. https://doi.org/10.1093/infdis/jiq118

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; Douek, Daniel C.

In: Journal of Infectious Diseases, Vol. 203, No. 6, 15.03.2011, p. 780-790.

Research output: Contribution to journalArticle

Sandler, NG, Wand, H, Roque, A, Law, M, Nason, MC, Nixon, DE, Pedersen, C, Ruxrungtham, K, Lewin, SR, Emery, S, Neaton, JD, Brenchley, JM, Deeks, SG, Sereti, I & Douek, DC 2011, 'Plasma levels of soluble CD14 independently predict mortality in HIV infection', Journal of Infectious Diseases, vol. 203, no. 6, pp. 780-790. https://doi.org/10.1093/infdis/jiq118
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. / Plasma levels of soluble CD14 independently predict mortality in HIV infection. In: Journal of Infectious Diseases. 2011 ; Vol. 203, No. 6. pp. 780-790.
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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.",
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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.

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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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