Markers of coagulation and inflammation often remain elevated in ART-treated HIV-infected patients

Current Opinion in HIV and AIDS

Volumn 9, Issue 1, 2014, Pages 80-86

  Funderburg, Nicholas T ^a,b  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b OHIO STATE UNIVERSITY   (United States)

Author keywords

antiretroviral therapy; coagulation; D dimer; inflammation

Indexed keywords

ABACAVIR; BIOLOGICAL MARKER; D DIMER; FIBRINOGEN; PADGEM PROTEIN; RALTEGRAVIR; THROMBOPLASTIN; VON WILLEBRAND FACTOR;

ARTERY THROMBOSIS; BLOOD CLOTTING; CARDIOVASCULAR RISK; CELL SURFACE; FIBRINOLYSIS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFLAMMATION; MORBIDITY; PRIORITY JOURNAL; REVIEW; THROMBOCYTE AGGREGATION; VIRUS REPLICATION;

ANTI-RETROVIRAL AGENTS; BIOLOGICAL MARKERS; BLOOD COAGULATION; HIV INFECTIONS; HUMANS; INFLAMMATION;

EID: 84892369987     PISSN: 1746630X     EISSN: 17466318     Source Type: Journal    
DOI: 10.1097/COH.0000000000000019     Document Type: Review

References (87)

1. Schulz C, Engelmann B, Massberg S. Crossroads of coagulation and innate immunity: The case of deep vein thrombosis. J Thromb Haemost 2013; 11 (Suppl 1): 233-241
2. Mackman N. Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol 2004; 24: 1015-1022
3. Mackman N. Role of tissue factor in hemostasis and thrombosis. Blood Cells Mol Dis 2006; 36: 104-107
4. Matta F, Yaekoub AY, Stein PD. Human immunodeficiency virus infection and risk of venous thromboembolism. Am J Med Sci 2008; 336: 402-406
5. Copur AS, Smith PR, Gomez V, et al. HIV infection is a risk factor for venous thromboembolism. AIDS Patient Care STDS 2002; 16: 205-209
6. Sullivan PS, Dworkin MS, Jones JL, Hooper WC. Epidemiology of thrombosis in HIV-infected individuals. The Adult/Adolescent Spectrum of HIV Disease Project. AIDS 2000; 14: 321-324
7. Fultz SL, McGinnis KA, Skanderson M, et al. Association of venous thromboembolism with human immunodeficiency virus and mortality in veterans. Am J Med 2004; 116: 420-423
8. Hsue PY, Giri K, Erickson S, et al. Clinical features of acute coronary syndromes in patients with human immunodeficiency virus infection. Circulation 2004; 109: 316-319
9. Hsue PY, Lo JC, Franklin A, et al. Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection. Circulation 2004; 109: 1603-1608
10. Tabib A, Leroux C, Mornex JF, Loire R. Accelerated coronary atherosclerosis and arteriosclerosis in young human-immunodeficiency-virus- positive patients. Coron Artery Dis 2000; 11: 41-46
11. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007; 92: 2506-2512
12. Feffer SE, Fox RL, Orsen MM, et al. Thrombotic tendencies and correlation with clinical status in patients infected with HIV. South Med J 1995; 88: 1126-1130
13. Bissuel F, Berruyer M, Causse X, et al. Acquired protein S deficiency: Correlation with advanced disease in HIV-1-infected patients. J Acquir Immune Defic Syndr 1992; 5: 484-489
14. Sorice M, Griggi T, Arcieri P, et al. Protein S and HIV infection. The role of anticardiolipin and antiprotein S antibodies. Thromb Res 1994; 73: 65-75
15. Mocroft A, Reiss P, Gasiorowski J, et al. Serious fatal and nonfatal non-AIDSdefining illnesses in Europe. J Acquir Immune Defic Syndr 2010; 55: 262-270
16. Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 2009; 338: A3172
17. El-Sadr WM, Lundgren J, Neaton JD, et al. CD4 count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355: 2283-2296
18. Jong E, Louw S, van Gorp EC, et al. The effect of initiating combined antiretroviral therapy on endothelial cell activation and coagulation markers in South African HIV-infected individuals. Thromb Haemost 2010; 104: 1228-1234
19. Lederman MM, Calabrese L, Funderburg NT, et al. Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis 2011; 204: 1217-1226
20. Neuhaus J, Jacobs DR Jr, Baker JV, et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis 2010; 201: 1788-1795
21. Sandler NG, Wand H, Roque A, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011; 203: 780-790
22. Levi M, van der Poll T. Two-way interactions between inflammation and coagulation. Trends Cardiovasc Med 2005; 15: 254-259
23. Levi M, van der Poll T, Buller HR. Bidirectional relation between inflammation and coagulation. Circulation 2004; 109: 2698-2704
24. Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 2012; 34: 43-62
25. Zhang C. The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol 2008; 103: 398-406
26. Mackman N. Regulation of the tissue factor gene. Faseb J 1995; 9: 883-889
27. Camerer E, Huang W, Coughlin SR. Tissue factor-And factor X-dependent activation of protease-Activated receptor 2 by factor VIIa. Proc Natl Acad Sci U S A 2000; 97: 5255-5260
28. Crum-Cianflone NF, Weekes J, Bavaro M. Thromboses among HIV-Infected Patients during the Highly Active Antiretroviral Therapy Era. AIDS Patient Care STDS 2008; 22: 771-778
29. Klein SK, Slim EJ, de Kruif MD, et al. Is chronic HIV infection associated with venous thrombotic disease? A systematic review. Neth J Med 2005; 63: 129-136
30. Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 2008; 5: E203
31. Duprez DA, Neuhaus J, Kuller LH, et al. Inflammation, coagulation and cardiovascular disease in HIV-infected individuals. PLoS One 2012; 7: E44454
32. Justice AC, Freiberg MS, Tracy R, et al. Does an index composed of clinical data reflect effects of inflammation, coagulation, and monocyte activation on mortality among those aging with HIV? Clin Infect Dis 2012; 54: 984-994
33. Musselwhite LW, Sheikh V, Norton TD, et al. Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. AIDS 2011; 25: 787-795
34. Ford ES, Greenwald JH, Richterman AG, et al. Traditional risk factors and D-dimer predict incident cardiovascular disease events in chronic HIV infection. AIDS 2010; 24: 1509-1517
35. Tracy RP. Inflammation markers and coronary heart disease. Curr Opin Lipidol 1999; 10: 435-441
36. Kannel WB. Overview of hemostatic factors involved in atherosclerotic cardiovascular disease. Lipids 2005; 40: 1215-1220
37. Fan ST, Edgington TS. Integrin regulation of leukocyte inflammatory functions. CD11b/CD18 enhancement of the tumor necrosis factor-Alpha responses of monocytes. J Immunol 1993; 150: 2972-2980
38. Perez RL, Ritzenthaler JD, Roman J. Transcriptional regulation of the interleukin-1beta promoter via fibrinogen engagement of the CD18 integrin receptor. Am J Respir Cell Mol Biol 1999; 20: 1059-1066
39. Madden E, Lee G, Kotler DP, et al. Association of antiretroviral therapy with fibrinogen levels in HIV-infection. AIDS 2008; 22: 707-715
40. Tien PC, Choi AI, Zolopa AR, et al. Inflammation and mortality in HIV-infected adults: Analysis of the FRAM study cohort. J Acquir Immune Defic Syndr 2010; 55: 316-322
41. Aukrust P, Bjornsen S, Lunden B, et al. Persistently elevated levels of von Willebrand factor antigen in HIV infection. Downregulation during highly active antiretroviral therapy. Thromb Haemost 2000; 84: 183-187
42. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006; 12: 1365-1371
43. Funderburg NT, Mayne E, Sieg SF, et al. Increased tissue factor expression on circulating monocytes in chronic HIV infection: Relationship to in vivo coagulation and immune activation. Blood 2010; 115: 161-167
44. Funderburg NT, Zidar DA, Shive C, et al. Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndromes. Blood 2012; 120: 4599-4608
45. Baker JV, Huppler Hullsiek K, Bradford RL, et al. Circulating levels of tissue factor microparticle procoagulant activity are reduced with antiretroviral therapy and are associated with persistent inflammation and coagulation activation among HIV-positive patients. J Acquir Immune Defic Syndr 2013; 63: 367-371
46. Armah KA, McGinnis K, Baker J, et al. HIV status, burden of comorbid disease, and biomarkers of inflammation, altered coagulation, and monocyte activation. Clin Infect Dis 2012; 55: 126-136
47. Pontrelli G, Martino AM, Tchidjou HK, et al. HIV is associated with thrombophilia and high D-dimer in children and adolescents. AIDS 2010; 24: 1145-1151
48. Taiwo B, Matining RM, Zheng L, et al. Associations of T cell activation and inflammatory biomarkers with virological response to darunavir/ritonavir plus raltegravir therapy. J Antimicrob Chemother 2013; 68: 1857-1861
49. Baker JV, Neuhaus J, Duprez D, et al. Changes in inflammatory and coagulation biomarkers: A randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection. J Acquir Immune Defic Syndr 2011; 56: 36-43
50. Stein JH, Klein MA, Bellehumeur JL, et al. Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation 2001; 104: 257-262
51. Solages A, Vita JA, Thornton DJ, et al. Endothelial function in HIV-infected persons. Clin Infect Dis 2006; 42: 1325-1332
52. Hsue PY, Hunt PW, Wu Y, et al. Association of abacavir and impaired endothelial function in treated and suppressed HIV-infected patients. AIDS 2009; 23: 2021-2027
53. Huang AL, Vita JA. Effects of systemic inflammation on endothelium-dependent vasodilation. Trends Cardiovasc Med 2006; 16: 15-20
54. Lopez M, San Roman J, Estrada V, et al. Endothelial dysfunction in HIV infection-The role of circulating endothelial cells, microparticles, endothelial progenitor cells and macrophages. AIDS Rev 2012; 14: 223-230
55. O'Brien M, Montenont E, Hu L, et al. Aspirin attenuates platelet activation and immune activation in HIV-1-infected subjects on antiretroviral therapy: A pilot study. J Acquir Immune Defic Syndr 2013; 63: 280-288
56. Mayne E, Funderburg NT, Sieg SF, et al. Increased platelet and microparticle activation in HIV infection: Upregulation of P-selectin and tissue factor expression. J Acquir Immune Defic Syndr 2012; 59: 340-346
57. Hileman CO, Longenecker CT, Carman TL, et al. Elevated D-dimer is independently associated with endothelial dysfunction: A cross-sectional study in HIV-infected adults on antiretroviral therapy. Antivir Ther 2012; 17: 1345-1349
58. Macfarlane SR, Seatter MJ, Kanke T, et al. Proteinase-Activated receptors. Pharmacol Rev 2001; 53: 245-282
59. Coughlin SR. Thrombin signalling and protease-Activated receptors. Nature 2000; 407: 258-264
60. Sower LE, Froelich CJ, Carney DH, et al. Thrombin induces IL-6 production in fibroblasts and epithelial cells. Evidence for the involvement of the seventransmembrane domain (STD) receptor for alpha-Thrombin. J Immunol 1995; 155: 895-901
61. Meier A, Alter G, Frahm N, et al. MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands. J Virol 2007; 81: 8180-8191
62. Jiang W, Lederman MM, Hunt P, et al. Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-Treated HIV infection. J Infect Dis 2009; 199: 1177-1185
63. Klatt NR, Funderburg NT, Brenchley JM. Microbial translocation, immune activation, and HIV disease. Trends Microbiol 2013; 21: 6-13
64. Marchetti G, Gori A, Casabianca A, et al. Comparative analysis of T-cell turnover and homeostatic parameters in HIV-infected patients with discordant immune-virological responses to HAART. AIDS 2006; 20: 1727-1736
65. Guha M, O'Connell MA, Pawlinski R, et al. Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression. Blood 2001; 98: 1429-1439
66. Shive CL, Biancotto A, Funderburg NT, et al. HIV-1 is not a major driver of increased plasma IL-6 levels in chronic HIV-1 disease. J Acquir Immune Defic Syndr 2012; 61: 145-152
67. Pandrea I, Cornell E, Wilson C, et al. Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates. Blood 2012; 120: 1357-1366
68. Baker JV, Brummel-Ziedins K, Neuhaus J, et al. HIV replication alters the composition of extrinsic pathway coagulation factors and increases thrombin generation. J Am Heart Assoc 2013; 2: E000264
69. Sabin CA, Worm SW, Weber R, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D: A: D study: A multicohort collaboration. Lancet 2008; 371: 1417-1426
70. Obel N, Farkas DK, Kronborg G, et al. Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: A population-based nationwide cohort study. HIV Med 2010; 11: 130-136
71. Brothers CH, Hernandez JE, Cutrell AG, et al. Risk of myocardial infarction and abacavir therapy: No increased risk across 52 GlaxoSmithKlinesponsored clinical trials in adult subjects. J Acquir Immune Defic Syndr 2009; 51: 20-28
72. Baum PD, Sullam PM, Stoddart CA, McCune JM. Abacavir increases platelet reactivity via competitive inhibition of soluble guanylyl cyclase. AIDS 2011; 25: 2243-2248
73. Satchell CS, O'Halloran JA, Cotter AG, et al. Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy. J Infect Dis 2011; 204: 1202-1210
74. Jong E, Meijers JC, van Gorp EC, et al. Markers of inflammation and coagulation indicate a prothrombotic state in HIV-infected patients with long-Term use of antiretroviral therapy with or without abacavir. AIDS Res Ther 2010; 7: 9
75. Martin A, Amin J, Cooper DA, et al. Abacavir does not affect circulating levels of inflammatory or coagulopathic biomarkers in suppressed HIV: A randomized clinical trial. AIDS 2010; 24: 2657-2663
76. Jacobson MC, Dezube BJ, Aboulafia DM. Thrombotic complications in patients infected with HIV in the era of highly active antiretroviral therapy: A case series. Clin Infect Dis 2004; 39: 1214-1222
77. Friis-Moller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356: 1723-1735
78. Friis-Moller N, Weber R, Reiss P, et al. Cardiovascular disease risk factors in HIV patients-Association with antiretroviral therapy. Results from the DAD study. AIDS 2003; 17: 1179-1193
79. Martinez E, D'Albuquerque PM, Llibre JM, et al. Changes in cardiovascular biomarkers in HIV-infected patients switching from ritonavir-boosted protease inhibitors to raltegravir. AIDS 2012; 26: 2315-2326
80. Bozzette SA, Ake CF, Tam HK, et al. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med 2003; 348: 702-710
81. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338: 853-860
82. Hsue PY, Scherzer R, Grunfeld C, et al. HIV infection is associated with decreased thrombin generation. Clin Infect Dis 2012; 54: 1196-1203
83. Haugaard AK, Lund TT, Birch C, et al. Discrepant coagulation profile in HIV-infection: Elevated D-dimer but impaired platelet aggregation and clot initiation. AIDS 2013. [Epub ahead of print
84. Hatano H, Delwart EL, Norris PJ, et al. Evidence of persistent low-level viremia in long-Term HAART-suppressed, HIV-infected individuals. AIDS 2010; 24: 2535-2539
85. Hunt PW, Martin JN, Sinclair E, et al. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4 T cell recovery on antiretroviral therapy. J Infect Dis 2011; 203: 1474-1483
86. Piconi S, Parisotto S, Rizzardini G, et al. Atherosclerosis is associated with multiple pathogenic mechanisms in HIV-infected antiretroviral-naive or treated individuals. AIDS 2013; 27: 381-389
87. Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005; 352: 48-62