Clinical utility of biomarkers of endothelial activation and coagulation for prognosis in HIV infection

Abstract

Introduction: HIV infection is associated with vascular dysfunction and adverse cardiovascular outcomes. Our objective was to review the evidence regarding the clinical utility of endothelial activation and coagulation biomarkers for the prognosis of HIV-infected patients.

Methods: We searched PubMed and Embase for publications using the keywords “HIV” or “HIV infection” and “endothelium” or “coagulation”. We reviewed reference lists and hand-searched for additional relevant articles. All clinical studies that enrolled non-pregnant, HIV-infected adults, measured biomarkers reflecting endothelial activation or coagulation, and prospectively evaluated their associations with vascular dysfunction or clinical outcomes were included.

Results: Seventeen studies were identified that fulfilled the inclusion criteria, of which 11 investigated endothelial activation biomarkers and 12 investigated coagulation biomarkers. Biomarkers and outcomes varied widely across studies. Overall, published studies support an association between P-selectin and venous thromboembolism in HIV-infected patients, an association between tissue-type plasminogen activator and death, and associations between D-dimer and several clinical outcomes, including venous thromboembolism, cardiovascular disease, and all-cause mortality.

Conclusions: Several studies have demonstrated associations between biomarkers of endothelial activation and coagulation and clinically important outcomes in HIV-1 infection. Additional large-scale prospective investigations to determine the utility of endothelial activation and coagulation biomarkers for risk stratification and prediction of adverse outcomes are clearly warranted.

Keywords: :

• HIV
• biomarker
• endothelium
• coagulation
• vascular dysfunction

Disclosure of Potential Conflicts of Interest

WCL is listed as a co-inventor on a patent applied for by the University Health Network (Toronto, ON Canada) to develop point-of-care tests for endothelial activation biomarkers in infectious diseases. All other authors report no conflict of interest.

Acknowledgments

Special thanks go to Sherry A Dodson, Clinical Librarian, University of Washington Health Sciences Library for her assistance with our search strategies. This work was supported by a New Investigator Award to SMG from the University of Washington Center for AIDS Research, which is funded by the National Institutes of Health (NIH) (P30 AI027757) and is supported by the following NIH Institutes and Centers: National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institute of Mental Health; National Institute on Drug Abuse; National Institute of Child Health and Human Development; National Heart, Lung, and Blood Institute; and National Institute on Aging; by the NIH (AI-58698 and AI-38518); and by a Canada Research Chair in Infectious Diseases and Inflammation to WCL from the Canadian Institutes for Health Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.