title: Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection.
abstract: BACKGROUND
  Activation and coagulation biomarkers were measured within the Strategies for Management of Antiretroviral Therapy (SMART) trial. Their associations with opportunistic disease (OD) in human immunodeficiency virus (HIV)-positive patients were examined.
  
  
  METHODS
  Inflammatory (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], amyloid-A, and amyloid-P) and coagulation (D-dimer and prothrombin-fragment 1+2) markers were determined. Conditional logistic regression analyses were used to assess associations between these biomarkers and risk of OD.
  
  
  RESULTS
  The 91 patients who developed an OD were matched to 182 control subjects. Patients with an hsCRP level > or =5 microg/mL at baseline had a 3.5 higher odds of OD (95% confidence interval [CI], 1.5-8.1) than did those with an hsCRP level <1 microg/mL (P=.003, by test for trend) and patients with an IL-6 level > or =3 pg/mL at baseline had a 2.4 higher odds of OD (95% CI, 1.0-5.4) than did those with an IL-6 level <1.5 pg/mL (P=.02, by test for trend). No other baseline biomarkers predicted development of an OD. Latest follow-up hsCRP level for those with an hsCRP level > or =5 microg/mL (compared with a level <1 microg/mL; odds ratio [OR], 7.6; 95% CI, 2.0-28.5; [P=.002, by test for trend), latest amyloid-A level for those with an amyloid-A level > or =6 mg/L (compared with a level <2 mg/L; OR, 3.8; 95% CI, 1.1-13.4; P=.03, by test for trend), and latest IL-6 level for those with an IL-6 level > or =3 pg/mL (compared with a level <1.5 pg/mL; OR 2.4; 95% CI, 0.7-8.8; P=.04, by test for trend) were also associated with development of an OD.
  
  
  CONCLUSIONS
  Higher IL-6 and hsCRP levels independently predicted development of OD. These biomarkers could provide additional prognostic information for predicting the risk of OD.
authors.affiliation: HIV Epidemiology and Biostatistics Group, Research Dept. of Infection and Population Health, UCL Medical School, University College London, London, UK. a.rodger@pcps.ucl.ac.uk
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Rodger
authors.forename: Zoe
authors.initials: Z
authors.lastname: Fox
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Christoph
authors.initials: C
authors.lastname: Boesecke
authors.forename: Daniela
authors.initials: D
authors.lastname: Gey
authors.forename: Athanassios
authors.initials: A
authors.lastname: Skoutelis
authors.forename: Matthew Bidwell
authors.initials: MB
authors.lastname: Goetz
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000378:metabolism*; D000328:Adult; D019380:Anti-HIV Agents; D015415:Biomarkers; D001777:Blood Coagulation / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D015850:Interleukin-6; D000685:Serum Amyloid A Protein; D000683:Serum Amyloid P-Component; D002097:C-Reactive Protein
references.citation: Cell Mol Life Sci. 2009 Jan;66(1):9-26
references.pmid: 18726069
references.citation: PLoS Med. 2008 Oct 21;5(10):e203
references.pmid: 18942885
references.citation: Nephrol Dial Transplant. 2002 Sep;17(9):1684-8
references.pmid: 12198224
references.citation: AIDS. 1998 Sep 10;12(13):1581-90
references.pmid: 9764776
references.citation: AIDS. 2000 May 26;14(8):951-8
references.pmid: 10853976
references.citation: BMC Cancer. 2001;1:19
references.pmid: 11710966
references.citation: Blood. 1993 Jun 15;81(12):3357-64
references.pmid: 8507873
references.citation: Br J Cancer. 2002 Dec 2;87(12):1437-44
references.pmid: 12454774
references.citation: J Infect Dis. 2000 Jan;181(1):51-7
references.pmid: 10608750
references.citation: AIDS. 2008 Feb 19;22(4):439-46
references.pmid: 18301056
references.citation: AIDS. 1991 May;5(5):505-11
references.pmid: 1677808
references.citation: Clin Exp Immunol. 2000 Apr;120(1):107-12
references.pmid: 10759771
references.citation: J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Oct 1;16(2):83-92
references.pmid: 9358102
references.citation: AIDS. 2007 Oct 1;21(15):2067-75
references.pmid: 17885297
references.citation: N Engl J Med. 2000 Mar 23;342(12):836-43
references.pmid: 10733371
references.citation: J Immunol. 1990 Jan 15;144(2):480-4
references.pmid: 2295799
references.citation: Am J Kidney Dis. 2006 Jan;47(1):139-48
references.pmid: 16377395
references.citation: J Immunol. 1992 Dec 1;149(11):3727-34
references.pmid: 1431144
references.citation: N Engl J Med. 2006 Nov 30;355(22):2283-96
references.pmid: 17135583
references.citation: J Infect Dis. 2008 Apr 15;197(8):1145-55
references.pmid: 18476293
references.citation: Arch Intern Med. 2006 Jan 9;166(1):64-70
references.pmid: 16401812
references.citation: J Acquir Immune Defic Syndr. 2002 Apr 1;29(4):346-55
references.pmid: 11917238
references.citation: Infect Immun. 1992 Oct;60(10):4245-52
references.pmid: 1328056
references.citation: HIV Clin Trials. 2008 May-Jun;9(3):177-85
references.pmid: 18547904
references.citation: J Infect Dis. 1999 Apr;179(4):843-8
references.pmid: 10068579
references.citation: J Infect Dis. 2002 Feb 15;185(4):456-62
references.pmid: 11865397
references.citation: Circulation. 2001 Feb 20;103(7):947-53
references.pmid: 11181468
references.citation: AIDS. 1998 Jun 18;12(9):1007-13
references.pmid: 9662196
references.citation: J Acquir Immune Defic Syndr. 2003 Feb 1;32(2):210-4
references.pmid: 12571532
references.citation: AIDS. 2004 Jan 2;18(1):51-8
references.pmid: 15090829
references.citation: Cancer Res. 2005 Jun 1;65(11):4673-82
references.pmid: 15930285