D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events

• Type of Material: Article
• Authors: Matthew S. Freiberg, Vanderbilt University; Ionut Bebu, George Washington University; Russell Tracy, University of Vermont; Kaku So-Armah, Boston University; Jason Okulicz, Uniformed Services University of the Health Sciences; Anuradha Ganesan, Uniformed Services University of the Health Sciences; Adam Armstrong, Uniformed Services University of the Health Sciences; Thomas O'Bryan, Uniformed Services University of the Health Sciences; David Rimland, Emory University; Amy C. Justice, Yale University; Brian K. Agan, Uniformed Services University of the Health Sciences; Infectious Disease Clinical Research Program HIV Working Group
• Language: English
• Date: 2016-04-18
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0152588
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 11
• Issue: 4
• Start Page: e0152588
• End Page: e0152588
• Grant/Funding Information: Support for this work (IDCRP-000-33) was provided by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DOD) program executed through the Uniformed Services University of the Health Sciences.; This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under Inter-Agency Agreement Y1-AI-5072.
• Keywords: Blood pressure; Science & Technology; Biomarkers; MYOCARDIAL-INFARCTION; DISEASE; Cholesterol; HIV; HIV infections; Multidisciplinary Sciences; COAGULATION; MARKERS; Antiretroviral therapy; INFECTED PATIENTS; INFLAMMATORY BIOMARKERS; Inflammatory diseases; Alcohol consumption; INTERLEUKIN-6
• Research Categories: Health Sciences, Epidemiology; Health Sciences, General; Health Sciences, Immunology

Abstract

The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimerand Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361 cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6-148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.