Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection - PubMed (original) (raw)

Randomized Controlled Trial

. 2009 Sep 15;200(6):973-83.

doi: 10.1086/605447.

Collaborators, Affiliations

Randomized Controlled Trial

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

Alison J Rodger et al. J Infect Dis. 2009.

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.

Trial registration: ClinicalTrials.gov NCT00027352.

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Conflict of interest statement

Conflict of interest statement: No member of the Writing Group for this report has any financial or personal relationships with people or organizations that could inappropriately influence this work or constitute a conflict of interest, although most members of the group have, at some stage in the past, received funding from a variety of pharmaceutical companies for research, travel grants, speaking engagements or consultancy fees.

Figures

Figure 1

Figure 1

  1. P-values are derived from a test for trend in the multivariable analysis (i.e. they evaluate the impact of moving from the reference group to the intermediate group to the group containing the highest level of each biomarker)
  2. Multivariable models are adjusted for: in A) baseline CD4+ counts and HIV-RNA levels, age and prior AIDS; in B) latest and baseline CD4+ counts and HIV-RNA levels, age and prior AIDS
  3. Multivariable analyses for CD4+ and HIV-RNA are only adjusted for age and prior AIDS

Figure 2

Figure 2

Odds ratios for opportunistic disease – comparisons between the DC arm and the VS arm

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