Activation and Coagulation Biomarkers Are Independent Predictors of the Development of Opportunistic Disease in Patients with HIV Infection

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 >= 5 mu g/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 mu g/mL (P = .003, by test for trend) and patients with an IL-6 level >= 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 >= 5 mu g/mL (compared with a level <1 mu g/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 >= 6 mg/L (compared with a leve <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 >= 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. Clinical trials registration. Clinical Trials.gov number NCT00027352.