title: D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events.
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-dimer and 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 361cells/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.
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University School of Medicine and Geriatric Research, Education, and Clinical Center, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, United States of America.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Freiberg
authors.affiliation: The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Rockville, MD, United States of America.
authors.forename: Ionut
authors.initials: I
authors.lastname: Bebu
authors.affiliation: Department of Pathology, University of Vermont College of Medicine, Burlington, VT, United States of America.
authors.forename: Russell
authors.initials: R
authors.lastname: Tracy
authors.affiliation: Division of General Internal Medicine, Boston University, Boston, MA, United States of America.
authors.forename: Kaku
authors.initials: K
authors.lastname: So-Armah
authors.affiliation: Infectious Disease Clinical Research Program (IDCRP), Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America.|Infectious Disease Service, San Antonio Military Medical Center, San Antonio, TX, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Okulicz
authors.affiliation: Infectious Disease Clinical Research Program (IDCRP), Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America.|Infectious Disease Clinic, Walter Reed National Military Medical Center, Bethesda, MD, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ganesan
authors.affiliation: Infectious Disease Clinical Research Program (IDCRP), Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America.|U.S. Naval Medical Research Unit No. 6 Peru, Lima, Peru.
authors.forename: Adam
authors.initials: A
authors.lastname: Armstrong
authors.affiliation: Infectious Disease Clinical Research Program (IDCRP), Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America.|Infectious Disease Service, San Antonio Military Medical Center, San Antonio, TX, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Bryan
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine and VA Medical Center, Atlanta, Georgia, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Rimland
authors.affiliation: Section of General Internal Medicine, Department of Medicine, Yale University School of Medicine, and VA Connecticut Healthcare System West Haven affiliation, New Haven, CT, United States of America.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.affiliation: Infectious Disease Clinical Research Program (IDCRP), Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Agan
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006678:HIV / Q000472:pathogenicity*; D015658:HIV Infections / Q000097:blood* / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D000069078:Seroconversion; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C508600:IL6 protein, human; D015850:Interleukin-6; C036309:fibrin fragment D