Role of inflammation in HIV-1 disease progression and prognosis

Critical Reviews in Clinical Laboratory Sciences

Volumn 51, Issue 2, 2014, Pages 98-111

  Ipp, Hayley ^a   Zemlin, Annalise E ^b   Erasmus, Rajiv T ^b   Glashoff, Richard H ^a  

^a STELLENBOSCH UNIVERSITY   (South Africa)

^b NATIONAL HEALTH LABORATORY SERVICE   (South Africa)

Author keywords

Cardiovascular disease; CD4 T cell apoptosis; Cytokines; HIV related lymphomas; Immune activation; Lymphoid tissue fibrosis; Non HIV associated diseases

Indexed keywords

BETA 2 MICROGLOBULIN; CD4 ANTIGEN; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 6; NEOPTERIN; PROTEIN BCL 6; T LYMPHOCYTE RECEPTOR;

ADAPTIVE IMMUNITY; AGING; ANTIGEN PRESENTING CELL; B CELL LYMPHOMA; CD4+ T LYMPHOCYTE; CERCOCEBUS; CHLOROCEBUS AETHIOPS; CHRONIC INFLAMMATION; CYTOMEGALOVIRUS INFECTION; CYTOTOXIC T LYMPHOCYTE; DENDRITIC CELL; DISEASE ASSOCIATION; DISEASE COURSE; HEPATITIS C; HIV ASSOCIATED DEMENTIA; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNE DEFICIENCY; IMMUNOPATHOGENESIS; IMMUNOREGULATION; INFLAMMATION; INNATE IMMUNITY; INTESTINE MUCOSA; LYMPHOID TISSUE; MEMORY T LYMPHOCYTE; MIXED INFECTION; MUCOSAL IMMUNITY; NATURAL HOST; NONHUMAN; PRIORITY JOURNAL; PROGNOSIS; PROTEIN BLOOD LEVEL; REVIEW; RHESUS MONKEY; SIMIAN IMMUNODEFICIENCY VIRUS; SOOTY MANGABEYS; T CELL DEPLETION; T LYMPHOCYTE ACTIVATION; UPREGULATION; VIRUS CARCINOGENESIS; VIRUS CELL INTERACTION; VIRUS ETIOLOGY; VIRUS IMMUNITY; VIRUS LATENCY; VIRUS REPLICATION; VIRUS TRANSMISSION;

DISEASE PROGRESSION; HIV INFECTIONS; HIV-1; HUMANS; INFLAMMATION; PROGNOSIS;

EID: 84897855916     PISSN: 10408363     EISSN: 1549781X     Source Type: Journal    
DOI: 10.3109/10408363.2013.865702     Document Type: Review

References (174)

1. Kelley CF, Kitchen CM, Hunt PW, et al. Incomplete peripheral CD4 cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 2009;48: 787-94.
2. Gaardbo JC, Hartling HJ, Gerstoft J, Nielsen SD. Incomplete immune recovery in HIV infection: mechanisms, relevance for clinical care, and possible solutions. Clin Dev Immunol 2012;2012:670957.
3. The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord (2012) CD4 Cell Count and the Risk of AIDS or Death in HIV-Infected Adults on Combination Antiretroviral Therapy with a Suppressed Viral Load: a Longitudinal Cohort Study from COHERE. PLoS Med 9: e1001194. doi:10.1371.
4. Available from: http://www.who.int/mediacentre/news/releases/2013/new- hiv-recommendations-20130630/en/[last accessed 26 November 2013].
5. Orsi F, Carrieri MP, Coriat B, et al. Call for action to secure universal access to ART in developing countries. Lancet 2010; 375:1693-4.
6. WHO. Progress report. Geneva: World Health Organization; 2009. Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. Available from: http://relief web.int/report/world/global-hivaids- response-epidemic-update-and-health-sector-progress-towards-universal [last accessed 26 November 2013].
7. Anthony KB, Yoder C, Metcalf JA, et al. Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly active antiretroviral therapy is associated with ongoing increased CD4 T cell activation and turnover. J Acquir Immune Defic Syndr 2003; 33:125-33.
8. Massanella M, Negredo E, Puig J, et al. Raltegravir intensification shows differing effects on CD8 and CD4 T cells in HIV-infected HAART-suppressed individuals with poor CD4 T-cell recovery. AIDS 2012;26:2285-93.
9. Moore DM, Hogg RS, Chan K, et al. Disease progression in patients with virological suppression in response to HAART is associated with the degree of immunological response. AIDS 2006;20:371-7.
10. Tan R, Westfall AO, Willig JH, et al. Clinical outcome of HIV-infected antiretroviral-naive patients with discordant immunologic and virologic responses to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2008;47:553-8.
11. Estes JD, Haase AT, Schacker TW. The role of collagen deposition in depleting CD4 T cells and limiting reconstitution in HIV-1 and SIV infections through damage to the secondary lymphoid organ niche. Semin Immunol 2008;20:181-6.
12. Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med 1981;305:1425-31.
13. Giorgi JV, Liu Z, Hultin LE, et al. Elevated levels of CD38 CD8 T cells in HIV infection add to the prognostic value of low CD4 T cell levels: results of 6 years of follow-up. J Acquir Immune Defic Syndr 1993;6:904-12.
14. Giorgi JV, Hultin LE, McKeating JA, et al. Shorter survival in advanced immunodeficiency virus type 1 infection is more closely associated with T-lymphocyte activation then with plasma virus burden or virus chemokine receptor usage. J Infect Dis 1999;179: 859-70.
15. The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4 count-guided interruption of antiretroviral treatment. N Engl J Med 2006;355:2283-96.
16. Kuller LH, Tracey R, Belloso W, et al. Activation of inflammatory and coagulation pathways is associated with mortality in patients with HIV infection. PLoS Med 2008;5:e203.
17. Engels EA, Pfeiffer RM, Goedert JJ, et al. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS 2006;20:1645-54.
18. El-Sadr W. Inflammation and HIV: a new paradigm. Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention, 19-22 July 2009. Cape Town, South Africa. Abstract MOPL104.
19. Hladik F, McElrath MJ. Setting the stage: host invasion by HIV. Nat Rev Immunol 2008;8:447-57.
20. Veazey R, Lackner A. The mucosal immune system and HIV-1 infection. AIDS Rev 2003;5:245-52.
21. Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol 2003;21:685-711.
22. Todryk SM, Melcher AA, Dalgleish AG, Vile RG. Heat shock proteins refine the danger theory. Immunology 2000;99:334-7.
23. Gay C, Dibben O, Anderson JA, et al. Cross-sectional detection of acute HIV infection: timing of transmission, inflammation and antiretroviral therapy. PLoS One 2011;6:e19617.
24. Leeansyah E, Malone DF, Anthony DD, Sandberg JK. Soluble biomarkers of HIV transmission, disease progression and comorbidities. Curr Opin HIV AIDS 2013;8:117-24.
25. Fahey JL, Taylor JM, Manna B, et al. Prognostic significance of plasma markers of immune activation, HIV viral load and CD4 T-cell measurements. AIDS 1998;12:1581-90.
26. Stacey AR, Norris PJ, Qin L, et al. Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J Virol 2009;83:3719-33.
27. Jiao Y, Zhang T, Wang R, et al. Plasma IP-10 is associated with rapid disease progression in early HIV-1 infection. Viral Immunol 2012;25:333-7.
28. Xu H, Wang X, Veazey RS. Mucosal immunology of HIV infection. Immunol Rev 2013;254:10-33.
29. Kelley CF, Barbour JD, Hecht FM. The relation between symptoms, viral load (VL), and viral load set point in primary HIV infection (PHI). J Acquir Immune Defic Syndr 2007;45: 445-8.
30. Sousa AE, Carneiro J, Meier-Schellersheim M, et al. CD4 T cell depletion is linked directly to immune activation in the patho-genesis of HIV-1 and HIV-2 but only indirectly to the viral load. J Immunol 2002;169:3400-6.
31. Deeks SG, Kitchen CM, Liu L, et al. Immune activation set point during early HIV infection predicts subsequent CD4 T-cell changes independent of viral load. Blood 2004;104:942-7.
32. Haase AT. Perils at mucosal front lines for HIV and SIV and their hosts. Nat Rev Immunol 2005;5:783-92.
33. Badley AD, Pilon AA, Landay A, Lynch DH. Mechanisms of HIV-associated lymphocyte apoptosis. Blood 2000;96:2951-64.
34. Cummins NW, Badley AD. Mechanisms of HIV-associated lymphocyte apoptosis. Cell Death Dis 2010;1, e99; doi:10.1038/cddis.2010.77.
35. Kramer HB, Lavender KJ, Qin L, et al. Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection. PLoS Pathog 2010;6:e1000893.
36. Fiebig EW, Wright DJ, Rawal BD, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 2003;17: 1871-9.
37. Haas A, Zimmermann K, Oxenius A. Antigen-dependent and-independent mechanisms of T and B cell hyperactivation during chronic HIV-1 infection. J Virol 2011;85:12102-13.
38. Silvestri G, Sodora DL, Koup RA, et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 2003;18:441-5.
39. Bosinger SE, Jacquelin B, Beneke A, et al. Systems biology of natural simian immunodeficiency virus infections. Curr Opin HIV AIDS 2012;7:71-8.
40. Bosinger SE, Li Q, Gordon SN, et al. Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J Clin Invest 2009;119:3556-72.
41. Jacquelin B, Mayau V, Targat B, et al. Nonpathogenic SIV infection of African green monkeys induces a strong, but rapidly controlled type I IFN response. J Clin Invest 2009;119: 3544-55.
42. Harris LD, Tabb B, Sodora DL, et al. Down regulation of robust acute type I interferon responses distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection of natural hosts from pathogenic SIV infection of rhesus macaques. J Virol 2010; 84:7886-91.
43. Kornfeld C, Ploquin MJ, Pandrea I, et al. Anti-inflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest 2005; 115:1082-91.
44. Estes, JD, Gordon SN, Zeng M, et al. Early resolution of acute immune activation and induction of PD-1 in SIV-infected sooty mangabeys distinguishes nonpathogenic from pathogenic iInfection in rhesus macaques. J Immunol 2008;180:6798-807.
45. Goldstein S, Ourmanov I, Brown CR, et al. Wide range of viral load in healthy African green monkeys naturally infected with simian immunodeficiency virus. J Virol 2000;74:11744-53.
46. Estes JD, Harris LD, Klatt NR, et al. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PloS Pathogen 2010;6: e1001052.
47. Paiardini M, Frank I, Pandrea I, et al. Mucosal immune dysfunction in AIDS pathogenesis. AIDS Rev 2008;10:36-46.
48. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006;12:1365-71.
49. Mehandru S, Poles MA, Tenner-Racz K, et al. Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection. PLoS Med 2006;3 PMID:17147468.
50. Tenorio A, Zheng E, Bosch R, et al. Soluble markers of inflammation and coagulation, but not T cell activation, predict non-AIDS-defining events during suppressive ART. 20th CROI, Atlanta, GA, 3-6 March 2013 (Abstract 790).
51. Sandler NG, Wand H, Roque A, et al, for the INSIGHT SMART Study Group. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011;203: 780-90.
52. Naeger DM, Martin JN, Sinclair E, et al. Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. PLoS One 2010;5:e8886.
53. Robain M, Boufassa F, Hubert JB, et al. Is cytomegalovirus infection a co-factor in HIV-1 disease progression? Epidemiol Infect 2000;125:415-20.
54. Deayton JR, Sabin CA, Johnson MA, et al. Importance of cytomegalovirus viraemia in risk of disease progression and death in HIV-infected patients receiving highly active antiretroviral therapy. Lancet 2004;363:2116-21.
55. 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: 1474-83.
56. Chang CC, Crane M, Zhou J, et al. HIV and co-infections. Immunol Rev 2013;254:114-42.
57. Modjarrad K, Vermund SH Effect of treating co-infections on HIV-1 viral load: a systematic review. Lancet Infect Dis 2010;10: 455-63.
58. Negredo E, Massanella M, Puig J, et al. Nadir CD4 T cell count as predictor and high CD4 T cell intrinsic apoptosis as final mechanism of poor CD4 T cell recovery in virologically suppressed HIV-infected patients: clinical implications. Clin Infect Dis 2010;50:1300-8.
59. Peters L, Mocroft A, Soriano V, et al. Hepatitis C virus coinfection does not influence the CD4 cell recovery in HIV-1-infected patients with maximum virologic suppression. J Acquir Immune Defic Syndr 2009;50:457-63.
60. Bentwich Z. Concurrent infections that rise the HIV viral load. J HIV Ther 2003;8:72-5.
61. + T cell depletion in human immunodeficiency virus (HIV) infection: role of apoptosis. Viruses 2011;3:586-612.
62. Buzon M, Massanella M, Llibre J, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 2010;16:460-5.
63. Gandhi RT, Zheng L, Bosch RJ, et al. The effect of Raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial. PLoS Med 2010;7(8):e1000321.
64. Hatano H, Hayes TL, Dahl V, et al. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis 2011;203:960-8.
65. Massanella M, Negredo E, Perez-Alvarez N, et al. CD4 T-cell hyperactivation and susceptibility to cell death determine poor CD4 T-cell recovery during suppressive HAART. AIDS 2010;24: 959-68.
66. Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol 2008;214: 231-41.
67. Alimonti JB, Ball TB, Fowke KR. Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus and AIDS. J Gen Virol 2003;84:1649-61.
68. Gougeon ML, Lecoeur H, Dulioust A, et al. Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression. J Immunol 1996;156:3509-20.
69. Van Parijs L, Refaeli Y, Lord JD, et al. Uncoupling IL-2 signals that regulate T cell proliferation, survival, and Fas-mediated activation-induced cell death. Immunity 1999;11:281-8.
70. Sloand EM, Young NS, Kumar P, et al. Role of Fas ligand and receptor in the mechanism of T cell depletion in AIDS: effect on CD4 lymphocyte depletion and HIV replication. Blood 1997;89: 1357-63.
71. Kaplan D, Sieg S. Role of the Fas/Fas ligand apoptotic pathway in HIV type 1 disease. J Virol 1998;72:6279-82.
72. Campbell GR, Watkins JD, Esquieu D, et al. The C terminus of HIV-1 Tat modulates the extent of CD178-mediated apoptosis of T cells. J Biol Chem 2005;280:38376-82.
73. Li-Weber M, Laur O, Dern K, Krammer PH. T cell activation-induced and HIV tat-enhanced CD95(APO-1/Fas) ligand transcription involves NF-KB. Eur J Immunol 2000;30:661-70.
74. Zheng L, Trageser CL, Willerford DM, Lenardo MJ. T cell growth cytokines cause the superinduction of molecules mediating antigen-induced T lymphocyte death. J Immunol 1998;160:763-9.
75. Lederman MM, Margolis L. The lymph node in HIV pathogenesis. Semin Immunol 2008;20:187-95.
76. Popovic M, Tenner-Racz K, Pelser C, et al. Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy. Proc Natl Acad Sci USA 2005;102:14807-12.
77. Petrovas C, Yamamoto T, Gerner MY, et al. CD4 T follicular helper cell dynamics during SIV infection. J Clin Invest 2012;122: 3281-94.
78. Lindqvist M, van Lunzen J, Soghoian DZ, et al. Expansion of HIV-specific T follicular helper cells in chronic HIV infection. J Clin Invest 2012;122:3271-80.
79. Perreau M, Savoye AL, De Crignis E, et al. Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J Exp Med 2013;210: 143-56.
80. Vinuesa CG. HIV and T follicular helper cells: a dangerous relationship. J Clin Invest 2012;122:3059-62.
81. Zeng M, Smith AJ, Wietgrefe SW, et al. Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. J Clin Invest 2011;121:998-1008.
82. Schacker T, Brenchley J, Beilman G, et al. Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4 T cells in human immunodeficiency virus type 1 infection. Clin Vaccine Immunol 2006;13:556-60.
83. Schaefer CJ, Ruhrmund DW, Pan L, et al. Antifibrotic activities of pirfenidone in animal models. Eur Respir Rev 2011;20:85-97.
84. Bouvard V, Baan R, Straif K, et al. on behalf of the WHO International Agency for Research on Cancer Monograph Working Group. A review of human carcinogens-Part B: biological agents. Lancet Oncol 2009;10:321-2.
85. Carbone A, Gloghini A. AIDS-related lymphomas: from patho-genesis to pathology. Br J Haematol 2005;130:662-70.
86. Ulrickson M, Oliver W, Casper C. Epidemiology, diagnosis, and treatment of HIV-associated non-Hodgkin lymphoma in resource-limited settings. Adv Hematol 2012. doi:10.1155/2012/932658.
87. Casper C. The increasing burden of HIV-associated malignancies in resource-limited regions. Annu Rev Med 2011;62:157-70.
88. Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med 2011;62:141-55.
89. Barrett L, Fowke KR, Grant MD. Cytomegalovirus, aging, and HIV: a perfect storm. AIDS Rev 2012;14:159-67.
90. Hsue PY, Deeks SG, Hunt PW. Immunologic basis of cardiovascular disease in HIV-infected adults. J Infect Dis 2012;205: S375-82.
91. Caron M, Auclairt M, Vissian A, et al. Contribution of mitochondrial dysfunction and oxidative stress to cellular premature senescence induced by antiretroviral thymidine analogues. Antivir Ther 2008;13:27-38.
92. Leensyah E, Cameron P, Solomon A, et al. Inhibition of telomerase activity by HIV nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging. J Infect Dis 2013;207:1157-65.
93. Lefèvre C, Auclair M, Boccara F, et al. Premature senescence of vascular cells is induced by HIV protease inhibitors: implication of prelamin A and reversion by statin. Arterioscler Thromb Vasc Biol 2010;30:2611-20.
94. Gannon P, Khan MZ, Kolson DL. Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol 2011;24:275-83.
95. Adle-Biassette H, Chretien F, Wingertsmann L, et al. Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage. Neuropathol Appl Neurobiol 1999;25:123-33.
96. Letendre SL, Ellis RJ, Ances BM, et al. Neurologic complications of HIV disease and their treatment. Top HIV Med 2010;18: 45-55.
97. Benjamin LA, Bryer A, Emsley HC, et al. HIV infection and stroke: current perspectives and future directions. Lancet Neurol 2012;11:878-90.
98. Saves M, Chene G, Ducimetiere P, et al. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus compared with the general population. Clin Infect Dis 2003; 37:292-8.
99. Zanni MV, Grinspoon SK. HIV-specific immune dysregulation and atherosclerosis. Curr HIV AIDS Rep 2012;9:200-5.
100. Cota-Gomez A, Flores NC, Cruz C, et al. The human immunodeficiency virus-1 Tat protein activates human umbilical vein endothelial cell E-selectin via an NF-kappa B-dependent mechanism. J Biol Chem 2002;277:14390-9.
101. Takano Y, Shimokado K, Hata Y, Yoshida M. HIV envelope protein gp120-triggered CD4 T-cell adhesion to vascular endothelium is regulated via CD4 and CXCR4 receptors. Biochem Biophys Acta 2007;1772:549-55.
102. Park IW, Ullrich CK, Schoenberger E, et al. HIV-1 Tat induces microvascular endothelial apoptosis through caspase activation. J Immunol 2001;167:2766-71.
103. Huang MB, Khan M, Garcia-Barro M, et al. Apoptotic effects in primary human umbilical vein endothelial cell cultures caused by exposure to virion-associated and cell membrane-associated HIV-1 gp120. J Acquir Immun Defic Syndr 2001;27: 213-21.
104. Tincati C, Bellistri GM, Casana M, et al. CD8 hyperactivation and senescence correlate with early carotid intima-media thickness in HIV patients with no cardiovascular disease. J Acquir Immune Defic Syndr 2009;51:642-4.
105. 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;92:2506-12.
106. Freiberg MS, Chang CH, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med 2013;173: 614-22.
107. Friis-Moller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2003; 348:702-10.
108. Wiedermann CJ, Kiechl S, Dunzendorfer S, et al. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study. J Am Coll Cardiol 1999;34:1975-81.
109. Pandrea I, Cornell E, Wilson C, et al. Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates. Blood 2012;120:1357-66.
110. Bilodeau ML, Simon DI. Clopidogrel for the hot patient. Circ Cardiovasc Interv 2009;2:495-6.
111. Matta F, Yaekoub AY, Stein PD. Human immunodeficiency virus infection and risk of venous thromboembolism. Am J Med Sci 2008;336:402-6.
112. Woollard KJ, Suhartoyo A, Harris EE, et al. Pathophysiological levels of soluble P-selectin mediate adhesion of leukocytes to the endothelium through Mac-1 activation. Circ Res 2008;103: 1128-38.
113. Ledwaba L, Tavel JA, Kahbo P, et al. Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. PLoS One 2012;7:e24243.
114. 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;115:161-7.
115. Giralt M, Domingo P, Villarroya F. Adipose tissue biology and HIV-infection. Best Pract Res Clin Endocrinol 2011;25: 487-99.
116. Gutierrez AD, Balasubramanyam A. Dysregulation of glucose metabolisms in HIV patients: epidemiology, mechanisms, and management. Endocrine 2012;41:1-10.
117. Samaras K. The burden of diabetes and hyperlipidemia in treated HIV infection and approaches for cardiometabolic care. Curr HIV AIDS Rep 2012;9:206-17.
118. De Wit S, Sabin C, Weber R, et al.; Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the data collection on adverse events of anti-HIV drugs (D:A:D) Study. Diabetes Care 2008;31:1224-9.
119. Hasse B, Ledergerber B, Furrer H, et al.; Swiss HIV Cohort Study. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis 2011;53:1130-9.
120. Milner KL, Van der Poorten D, Trenell M, et al. Chronic hepatitis C is associated with peripheral rather than hepatic insulin resistance. Gastroenterology 2010;138:932-41.
121. Mehta SH, Moore R, Thomas DL, et al. The effect of HAART and HCV infection on the development of hyperglycemia among HIV-infected persons. J Acquir Immune Defic Syndr 2003;33: 577-84.
122. Gupta S, Shenoy V, Bairy I, et al. Diabetes mellitus and HIV as co-morbidities in tuberculosis patients of rural south India. J Infect Public Health 2011;4:140-4.
123. Powderly WG. Osteoporosis and bone health in HIV. Curr HIV AIDS Rep 2012;9:218-22.
124. Kanis JA, Borgstrom C, De Laet H, et al. Assessment of fracture risk. Osteoporos Int 2005;16:581-89.
125. Haney EM, Warden SJ, Bliziotes MM. The effects of selective serotonin reuptake inhibitors on bone health in adults: time for recommendations about screening, prevention and management. Bone 2010;46:13-17.
126. Fakruddin JM, Laurence J. HIV envelope gp 120-mediated regulation of osteoclastogenesis via receptor activator of nuclear factor kappa B ligand (RANKL) secretion and its modulation by certain HIV protease inhibitors through interferon-gamma/RANKLK cross-talk. J Biol Chem 2003;278:48251-8.
127. Fakruddin JM, Laurence J. HIV-1 Vpr enhances production of receptor of activated NF-kappa B ligand (RANKL) via potentiation of glucocorticoid receptor activity. Arch Virol 2005;150:67-78.
128. Cotter EJ, Malizia AP, Chew N, et al. HIV proteins regulate bone marker secretion and transcription factor activity in cultured human osteoblasts with consequent potential implications for osteoblast function and development. AIDS Res Hum Retroviruses 2007;23:1521-30.
129. Anderson DM, Maraskovsky E, Billingsley WL, et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic cell function. Nature 1997;390:175-9.
130. Ofotokun I, McIntosh E, Weitzmann MN. HIV: inflammation and bone. Curr HIV AIDS Rep 2012;9:16-25.
131. Zou W, Bar-Shavit Z. Dual modulation of osteoclast differentiation by lipopolysaccharide. J Bone Miner Res 2002;17:1211-8.
132. Gutiérrez F, Masiá M. The role of HIV and antiretroviral therapy in bone disease. AIDS Rev 2011;13:109-18.
133. Mouly S, Lown KS, Kornhauser D, et al. Hepatic but not intestinal CP-P3A4 displays dose-dependent induction by efavirenz in humans. Clin Pharmacol Ther 2002;72:1-9.
134. Gupta S. Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. AIDS Patient Care STDS 2008;22:99-103.
135. Maggi P, Bartolozzi D, Bonfanti P, et al. Renal complications in HIV disease: between present and future. AIDS Rev 2012;14: 37-53.
136. Selick R, Byers R, Dworkin M. Trends in diseases reported on U.S. death certificates that mentioned HIV infection, 1987-1999. J Acqir Immune Defic Syndr 2006;43:378-87.
137. Déti E, Thiébaut R, Bonnet F, et al. Prevalence and factors associated with renal impairment in HIV-infected patients, ANRS C03 Aquitaine Cohort, France. HIV Med 2010;11:308-17.
138. Fernando S, Finkelstein F, Moore B, Weissmann S. Prevalence of chronic kidney disease in an urban HIV infected population. Am J Med Sci 2008;335:89-94.
139. Atta M. Diagnosis and natural history of HIV-associated nephropathy. Adv Chronic Kidney Dis 2010;17:52-8.
140. Marras D, Bruggeman LA, Gao F, et al. Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy. Nat Med 2002;8:522-6.
141. th Conference on Retroviruses and Opportunistic Infections), San Francisco, CA, USA, February 2010.
142. Fischer MJ, Wyatt CM, Gordon K, et al. Hepatitis C and the risk of kidney disease and mortality in veterans with HIV. J Acquir Immune Defic Syndr 2010;53:222-6.
143. Soriano V, Puoti M, Sulkowski M, et al. Care of patients coinfected with HIV and HCV: 2007 updated recommendations from the HCV-HIV International Panel. AIDS 2007;21:1073-89.
144. Puoti M, Moioli MC, Travi G, Rosootti R. The burden of liver disease in HIV-infected patients. Semin Liver Dis 2012;32:103-13.
145. Dore G, Soriano V, Rockstroh J, et al. Frequent HBV rebound among HIV-HBV coinfected patients following antiretroviral treatment interruption. AIDS 2010;24:1479-85.
146. Soriano V, Barreiro P, Sherman KE. The changing epidemiology of liver disease in HIV patients. AIDS Rev 2013;15:25-31.
147. Lin W, Weinberg EJ, Chung RT. Pathogenesis of accelerated fibrosis in HIV/HCV co-infection. J Infect Dis 2013;207:S13-18.
148. Cutrell J, Bedimo R. Non-AIDS defining cancers among HIV-infected patients. Curr HIV AIDS Rep 2013;10:207-16.
149. Dubrow R, Silverberg MJ, Park LS, et al. HIV infection, aging, and immune function: implications for cancer risk and prevention. Curr Opin Oncol 2012;24:506-16.
150. Engels EA, Biggar RJ, Hall HI, et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer 2008;123:187-94.
151. Harrod R, Nacsa J, Van Lint C, et al. Human immunodeficiency virus type-1 Tat/co-activator acetyltransferase interactions inhibit p53Lys-320 acetylation and p53-responsive transcription. J Biol Chem 2003;278:12310-8.
152. Campioni D, Corallini A, Zauli G, et al. HIV type 1 extracellular Tat protein stimulates growth and protects cells of BK virus/tat transgenic mice from apoptosis. AIDS Res Hum Retroviruses 1995;11:1039-48.
153. Colombrino E, Rossi E, Ballon G, et al. Human immunodeficiency virus type 1 Tat protein modulates cell cycle and apoptosis in Epstein-Barr virus-immortalized B Cells. Exp Cell Res 2004; 295:539-48.
154. Wistuba II, Behrens C, Milchgrub S, et al. Comparison of molecular changes in lung cancers in HIV-positive and HIV-indeterminate subjects. JAMA 1998;279:1554-9.
155. Tyerman Z, Aboulafia DM. Review of screening guidelines for non-AIDS-defining malignancies: evoking issues in the era of highly active antiretroviral therapy. AIDS Rev 2012;14:3-16.
156. Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009;360:1815-26.
157. Hunt PW, Deeks SG. Immune-based therapy for HIV infection: are acute and chronic HIV infection different diseases? J Infect Dis 2006;194:1632-4.
158. Lederman MM, Smeaton L, Smith KY, et al. Cyclosporin A provides no sustained immunologic benefit to persons with chronic HIV-1 infection starting suppressive antiretroviral therapy: results of randomized, controlled trial of the AIDS Clinical Trials Group. J Infect Dis 2006;194:1677-85.
159. Kvale D, Ormaasen V, Kran AM, et al. Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment. AIDS 2006;20:813-20.
160. Pettersen FO, Torheim EA, Dahm AEA, et al. Old drugs, new tricks-how some anti-inflammatory drugs can be used to treat HIV an exploratory trial of cyclooxygenase type 2 Inhibitor in HIV-1 infection: down regulated immune activation and improved T cell-dependent vaccine responses. J Virol 2011;85:6557-66.
161. Piconi S, Parisotto S, Rizzardini G, et al. Hydroxychloroquine drastically reduces immune activation in HIV-infected, ART-treated, immunological non responders. Blood 2011;118: 3263-72.
162. Weitz-Schmidt G. Statins as anti-inflammatory agents. Trends Pharmacol Sci 2002;23:482-6.
163. Ganesan A, Crum-Cianflone N, Higgins J, et al. High dose Atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial. J Infect Dis 2011; 203:756-64.
164. Ridker PM, Danielson E, Fonseca FAH, et al. for the JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359: 2195-207.
165. Carr A. Statins as anti-inflammatory therapy in HIV disease? J Infect Dis 2011;203:751-2.
166. Kopp E, Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 1994;265:956-9.
167. Tornero C, Ventura A, Mafe M. Aspirin is indicated for primary prevention of cardiovascular events in HIV-infected patients. J Acquir Immune Defic Syndr 2010;54:560.
168. Hileman CO, Carman TL, Gripshover BM, et al. Salsalate is poorly tolerated and fails to improve endothelial function in virologically suppressed HIV-infected adults. AIDS 2010;24: 1958-61.
169. Zhao Q. Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases. J Leukoc Biol 2010; 88:41-55.
170. Martin DE, Palleja S, Gathe J, et al. TBR-652, a potent dual chemokine receptor 5/chemokine receptor 2 (CCR5/CCR2) antagonist in phase 2 development for treatment of HIV infection. In: Program and abstracts of the 18th International Conference on AIDS, 18-23 July 2010, Vienna, Austria. Abstract MOAB0104.
171. French MA, King MS, Tschampa JM, et al. Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4 T cells. J Infect Dis 2009;200: 1212-15.
172. Méndez-Lagares G, Romero-Sánchez MC, Ruiz-Mateos E, et al. Long-term suppressive combined antiretroviral treatment did not normalize the serum level of soluble CD14. J Infect Dis 2013;207: 1221-5.
173. Ipp H, Zemlin AE, Glashoff RH, et al. Serum adenosine deaminase and total immunoglobulin G correlate with markers of immune activation and inversely with CD4 counts in asymptomatic, treatment-naïve HIV infection. J Clin Immunol 2013;33:605-12.
174. Cassol E, Malfeld S, Mahasha P, et al. Persistent microbial translocation and immune activation in HIV-1-infected South Africans on combination antiretroviral therapy (cART). J Infect Dis 2010;202:723-33.