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PLoS One. 2016 Apr 18;11(4):e0152588. doi: 10.1371/journal.pone.0152588. eCollection 2016.

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

Author information

1
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.
2
The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Rockville, MD, United States of America.
3
Department of Pathology, University of Vermont College of Medicine, Burlington, VT, United States of America.
4
Division of General Internal Medicine, Boston University, Boston, MA, United States of America.
5
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.
6
Infectious Disease Service, San Antonio Military Medical Center, San Antonio, TX, United States of America.
7
Infectious Disease Clinic, Walter Reed National Military Medical Center, Bethesda, MD, United States of America.
8
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America.
9
U.S. Naval Medical Research Unit No. 6 Peru, Lima, Peru.
10
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine and VA Medical Center, Atlanta, Georgia, United States of America.
11
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.

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.

PMID:
27088215
PMCID:
PMC4835105
DOI:
10.1371/journal.pone.0152588
[Indexed for MEDLINE]
Free PMC Article

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