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

• 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
• Journal Title: PLoS ONE
• Volume: Volume 11, Number 4
• Publisher: Public Library of Science | 2016-04-18, Pages e0152588-e0152588
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0152588
• Subjects: Health Sciences, Epidemiology; Health Sciences, Immunology; Health Sciences, General
• Keywords: Science & Technology; Multidisciplinary Sciences; MYOCARDIAL-INFARCTION; INFLAMMATORY BIOMARKERS; INFECTED PATIENTS; DISEASE; INTERLEUKIN-6; COAGULATION; MARKERS; HIV; Biomarkers; Antiretroviral therapy; HIV infections; Inflammatory diseases; Cholesterol; Blood pressure; Alcohol consumption

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.