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ABSTRACT: Background
Coagulation activity among persons with HIV is associated with end-organ disease risk, but the pathogenesis is not well characterized. We tested a hypothesis that hypercoagulation contributes to disease risk, in part, via upregulation of inflammation.Methods
Treatment effects of edoxaban (30 mg), a direct factor Xa inhibitor, vs placebo were investigated in a randomized, double-blind crossover trial among participants with HIV and viral suppression and D-dimer levels ≥100 ng/mL. During each 4-month crossover period, blood measures of coagulation, inflammation, and immune activation were assessed. Analyses of change on edoxaban vs change on placebo used linear mixed models.Results
Forty-four participants were randomized, and 40 completed at least 1 visit during each study period. The mean age was 49 years, and the CD4+ count was 739 cells/mm3. Edoxaban treatment led to declines in D-dimer (44%) and thrombin-antithrombin complex (26%) but did not lower inflammatory or immune activation measures. More bruising or bleeding events occurred during edoxaban (n = 28) than during placebo or no drug periods (n = 15).Conclusions
The direct factor Xa inhibitor edoxaban led to a substantial reduction in coagulation but no effect on inflammation or immune activation. These results do not support that hypercoagulation contributes to ongoing inflammation during chronic antiretroviral therapy-treated HIV disease.
SUBMITTER: Baker JV
PROVIDER: S-EPMC7008475 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Baker Jason V JV Wolfson Julian J Peterson Tess T Mooberry Micah M Gissel Matthew M Mystakelis Harry H Henderson Michael W MW Garcia-Myers Kelly K Rhame Frank S FS Schacker Timothy W TW Brummel-Ziedins Kathleen E KE Sereti Irini I Key Nigel S NS Tracy Russell P RP
Open forum infectious diseases 20200201 2
<h4>Background</h4>Coagulation activity among persons with HIV is associated with end-organ disease risk, but the pathogenesis is not well characterized. We tested a hypothesis that hypercoagulation contributes to disease risk, in part, via upregulation of inflammation.<h4>Methods</h4>Treatment effects of edoxaban (30 mg), a direct factor Xa inhibitor, vs placebo were investigated in a randomized, double-blind crossover trial among participants with HIV and viral suppression and D-dimer levels ≥ ...[more]