Factor Xa inhibition reduces coagulation activity but not inflammation among people with HIV: A randomized clinical trial

Jason V. Baker; Julian Wolfson; Tess Peterson; Micah Mooberry; Matthew Gissel; Harry Mystakelis; Michael W. Henderson; Kelly Garcia-Myers; Frank S. Rhame; Timothy W. Schacker; Kathleen E. Brummel-Ziedins; Irini Sereti; Nigel S. Key; Russell P. Tracy

doi:10.1093/ofid/ofaa026

Factor Xa inhibition reduces coagulation activity but not inflammation among people with HIV: A randomized clinical trial

Jason V. Baker, Julian Wolfson, Tess Peterson, Micah Mooberry, Matthew Gissel, Harry Mystakelis, Michael W. Henderson, Kelly Garcia-Myers, Frank S. Rhame, Timothy W. Schacker, Kathleen E. Brummel-Ziedins, Irini Sereti, Nigel S. Key, Russell P. Tracy

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Article number	ofaa026
Journal	Open Forum Infectious Diseases
Volume	7
Issue number	2
DOIs	https://doi.org/10.1093/ofid/ofaa026
State	Published - Feb 1 2020

Bibliographical note

Funding Information:
Financial support. This study was funded by the National Heart Lung and Blood Institute (National Heart, Lung, and Blood Institute/National Institutes of Health: R01 HL126542). The study drug was provided by Daiichi-Sankyo Pharmaceuticals. The work of I.S. and H.M. was supported by the intramural research program of National Institute of Allergy and Infectious Diseases/National Institutes of Health.

Funding Information:
This study was funded by the National Heart Lung and Blood Institute (National Heart, Lung, and Blood Institute/National Institutes of Health: R01 HL126542). The study drug was provided by Daiichi-Sankyo Pharmaceuticals. The work of I.S. and H.M. was supported by the intramural research program of National Institute of Allergy and Infectious Diseases/National Institutes of Health.

Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

Coagulation
HIV
Immune activation
Inflammation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Baker, J. V., Wolfson, J., Peterson, T., Mooberry, M., Gissel, M., Mystakelis, H., Henderson, M. W., Garcia-Myers, K., Rhame, F. S., Schacker, T. W., Brummel-Ziedins, K. E., Sereti, I., Key, N. S., & Tracy, R. P. (2020). Factor Xa inhibition reduces coagulation activity but not inflammation among people with HIV: A randomized clinical trial. Open Forum Infectious Diseases, 7(2), [ofaa026]. https://doi.org/10.1093/ofid/ofaa026

Baker, JV, Wolfson, J, Peterson, T, Mooberry, M, Gissel, M, Mystakelis, H, Henderson, MW, Garcia-Myers, K, Rhame, FS, Schacker, TW, Brummel-Ziedins, KE, Sereti, I, Key, NS & Tracy, RP 2020, 'Factor Xa inhibition reduces coagulation activity but not inflammation among people with HIV: A randomized clinical trial', Open Forum Infectious Diseases, vol. 7, no. 2, ofaa026. https://doi.org/10.1093/ofid/ofaa026

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title = "Factor Xa inhibition reduces coagulation activity but not inflammation among people with HIV: A randomized clinical trial",

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.",

keywords = "Coagulation, HIV, Immune activation, Inflammation",

author = "Baker, {Jason V.} and Julian Wolfson and Tess Peterson and Micah Mooberry and Matthew Gissel and Harry Mystakelis and Henderson, {Michael W.} and Kelly Garcia-Myers and Rhame, {Frank S.} and Schacker, {Timothy W.} and Brummel-Ziedins, {Kathleen E.} and Irini Sereti and Key, {Nigel S.} and Tracy, {Russell P.}",

note = "Funding Information: Financial support. This study was funded by the National Heart Lung and Blood Institute (National Heart, Lung, and Blood Institute/National Institutes of Health: R01 HL126542). The study drug was provided by Daiichi-Sankyo Pharmaceuticals. The work of I.S. and H.M. was supported by the intramural research program of National Institute of Allergy and Infectious Diseases/National Institutes of Health. Funding Information: This study was funded by the National Heart Lung and Blood Institute (National Heart, Lung, and Blood Institute/National Institutes of Health: R01 HL126542). The study drug was provided by Daiichi-Sankyo Pharmaceuticals. The work of I.S. and H.M. was supported by the intramural research program of National Institute of Allergy and Infectious Diseases/National Institutes of Health. Publisher Copyright: {\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2020",

month = feb,

day = "1",

doi = "10.1093/ofid/ofaa026",

language = "English (US)",

volume = "7",

journal = "Open Forum Infectious Diseases",

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TY - JOUR

T1 - Factor Xa inhibition reduces coagulation activity but not inflammation among people with HIV

T2 - A randomized clinical trial

AU - Baker, Jason V.

AU - Wolfson, Julian

AU - Peterson, Tess

AU - Mooberry, Micah

AU - Gissel, Matthew

AU - Mystakelis, Harry

AU - Henderson, Michael W.

AU - Garcia-Myers, Kelly

AU - Rhame, Frank S.

AU - Schacker, Timothy W.

AU - Brummel-Ziedins, Kathleen E.

AU - Sereti, Irini

AU - Key, Nigel S.

AU - Tracy, Russell P.

N1 - Funding Information: Financial support. This study was funded by the National Heart Lung and Blood Institute (National Heart, Lung, and Blood Institute/National Institutes of Health: R01 HL126542). The study drug was provided by Daiichi-Sankyo Pharmaceuticals. The work of I.S. and H.M. was supported by the intramural research program of National Institute of Allergy and Infectious Diseases/National Institutes of Health. Funding Information: This study was funded by the National Heart Lung and Blood Institute (National Heart, Lung, and Blood Institute/National Institutes of Health: R01 HL126542). The study drug was provided by Daiichi-Sankyo Pharmaceuticals. The work of I.S. and H.M. was supported by the intramural research program of National Institute of Allergy and Infectious Diseases/National Institutes of Health. Publisher Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2020/2/1

Y1 - 2020/2/1

N2 - 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.

AB - 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.

KW - Coagulation

KW - HIV

KW - Immune activation

KW - Inflammation

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VL - 7

JO - Open Forum Infectious Diseases

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ER -

Factor Xa inhibition reduces coagulation activity but not inflammation among people with HIV: A randomized clinical trial

Abstract

Bibliographical note

Keywords

UN SDGs

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