Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection

Alison J Rodger; Zoe Fox; Jens Lundgren; Lewis H Kuller; Christoph Boesecke; Daniela Gey; Athanassios Skoutelis; Matthew Bidwell Goetz; Andrew N Phillips; INSIGHT Strategies for Management of Antiretroviral Therapy (SMART) Study Group

doi:10.1086/605447

Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection

Alison J Rodger, Zoe Fox, Jens Lundgren, Lewis H Kuller, Christoph Boesecke, Daniela Gey, Athanassios Skoutelis, Matthew Bidwell Goetz, Andrew N Phillips, INSIGHT Strategies for Management of Antiretroviral Therapy (SMART) Study Group

Department of Immunology and Microbiology

121 Citations (Scopus)

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.

Original language	English
Journal	Journal of Infectious Diseases
Volume	200
Issue number	6
Pages (from-to)	973-83
Number of pages	11
ISSN	0022-1899
DOIs	https://doi.org/10.1086/605447
Publication status	Published - 2009

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Rodger, A. J., Fox, Z., Lundgren, J., Kuller, L. H., Boesecke, C., Gey, D., Skoutelis, A., Goetz, M. B., Phillips, A. N., & INSIGHT Strategies for Management of Antiretroviral Therapy (SMART) Study Group (2009). Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection. Journal of Infectious Diseases, 200(6), 973-83. https://doi.org/10.1086/605447

Rodger, AJ, Fox, Z, Lundgren, J, Kuller, LH, Boesecke, C, Gey, D, Skoutelis, A, Goetz, MB, Phillips, AN & INSIGHT Strategies for Management of Antiretroviral Therapy (SMART) Study Group 2009, 'Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection', Journal of Infectious Diseases, vol. 200, no. 6, pp. 973-83. https://doi.org/10.1086/605447

@article{9eac4d807ea511df928f000ea68e967b,

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.",

author = "Rodger, {Alison J} and Zoe Fox and Jens Lundgren and Kuller, {Lewis H} and Christoph Boesecke and Daniela Gey and Athanassios Skoutelis and Goetz, {Matthew Bidwell} and Phillips, {Andrew N} and {INSIGHT Strategies for Management of Antiretroviral Therapy (SMART) Study Group}",

note = "Keywords: AIDS-Related Opportunistic Infections; Adult; Anti-HIV Agents; Biological Markers; Blood Coagulation; C-Reactive Protein; Case-Control Studies; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Odds Ratio; Risk Factors; Serum Amyloid A Protein; Serum Amyloid P-Component",

year = "2009",

doi = "10.1086/605447",

language = "English",

volume = "200",

pages = "973--83",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection

AU - Rodger, Alison J

AU - Fox, Zoe

AU - Lundgren, Jens

AU - Kuller, Lewis H

AU - Boesecke, Christoph

AU - Gey, Daniela

AU - Skoutelis, Athanassios

AU - Goetz, Matthew Bidwell

AU - Phillips, Andrew N

AU - INSIGHT Strategies for Management of Antiretroviral Therapy (SMART) Study Group

N1 - Keywords: AIDS-Related Opportunistic Infections; Adult; Anti-HIV Agents; Biological Markers; Blood Coagulation; C-Reactive Protein; Case-Control Studies; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Odds Ratio; Risk Factors; Serum Amyloid A Protein; Serum Amyloid P-Component

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1086/605447

DO - 10.1086/605447

M3 - Journal article

C2 - 19678756

SN - 0022-1899

VL - 200

SP - 973

EP - 983

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 6

ER -

Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection

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