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

Freiberg MS, Bebu I, Tracy R, So-Armah K, Okulicz J, Ganesan A, Armstrong A, O'Bryan T, Rimland D, Justice AC, Agan BK, Infectious Disease Clinical Research Program HIV Working Gro - PLoS ONE (2016)

Bottom Line: This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03).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.

View Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

Population mean D-Dimer and IL-6 at the three time points.Box and whisker plot describes median (line inside of box), lower and upper quartiles (bottom and top of box), minimum (horizontal line below vertical dashed line), maximum (horizontal line above vertical dashed line) and outliers (open circles) for D-dimer and IL-6 distributions.
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pone.0152588.g001: Population mean D-Dimer and IL-6 at the three time points.Box and whisker plot describes median (line inside of box), lower and upper quartiles (bottom and top of box), minimum (horizontal line below vertical dashed line), maximum (horizontal line above vertical dashed line) and outliers (open circles) for D-dimer and IL-6 distributions.

Mentions: In unadjusted analyses, post-ART initiation (TP3) population median D-dimer levels were significantly higher than pre-HIV seroconversion levels (TP1), showing evidence of a “residual” elevation in D-dimer (Fig 1). 59% of subjects had TP3 D-dimer levels higher than baseline (TP1), while 41% of subjects had levels at or below baseline (TP1). After ART initiation and viral suppression (TP3), D-dimer levels were significantly lower compared to D-dimer levels at TP2 (Table 1). Pre-ART initiation (TP2) D-dimer levels were significantly higher than levels at TP1 and TP3 (p<0.01 for both). By comparison, the differences in IL-6 levels across the three time points were not statistically different (Fig 1, p>0.05 for all).


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

Freiberg MS, Bebu I, Tracy R, So-Armah K, Okulicz J, Ganesan A, Armstrong A, O'Bryan T, Rimland D, Justice AC, Agan BK, Infectious Disease Clinical Research Program HIV Working Gro - PLoS ONE (2016)

Population mean D-Dimer and IL-6 at the three time points.Box and whisker plot describes median (line inside of box), lower and upper quartiles (bottom and top of box), minimum (horizontal line below vertical dashed line), maximum (horizontal line above vertical dashed line) and outliers (open circles) for D-dimer and IL-6 distributions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835105&req=5

pone.0152588.g001: Population mean D-Dimer and IL-6 at the three time points.Box and whisker plot describes median (line inside of box), lower and upper quartiles (bottom and top of box), minimum (horizontal line below vertical dashed line), maximum (horizontal line above vertical dashed line) and outliers (open circles) for D-dimer and IL-6 distributions.
Mentions: In unadjusted analyses, post-ART initiation (TP3) population median D-dimer levels were significantly higher than pre-HIV seroconversion levels (TP1), showing evidence of a “residual” elevation in D-dimer (Fig 1). 59% of subjects had TP3 D-dimer levels higher than baseline (TP1), while 41% of subjects had levels at or below baseline (TP1). After ART initiation and viral suppression (TP3), D-dimer levels were significantly lower compared to D-dimer levels at TP2 (Table 1). Pre-ART initiation (TP2) D-dimer levels were significantly higher than levels at TP1 and TP3 (p<0.01 for both). By comparison, the differences in IL-6 levels across the three time points were not statistically different (Fig 1, p>0.05 for all).

Bottom Line: This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03).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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus