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Inflammatory Co-morbidities in HIV+ Individuals: Learning Lessons from Healthy Ageing

Abstract

Increased life expectancy due to improved efficacy of cART has uncovered an increased risk of age-related morbidities in HIV+ individuals and catalyzed significant research into mechanisms driving these diseases. HIV infection increases the risk of non-communicable diseases common in the aged, including cardiovascular disease, neurocognitive decline, non-AIDS malignancies, osteoporosis, and frailty. These observations suggest that HIV accelerates immunological ageing, and there are many immunological similarities with the aged, including shortened telomeres, accumulation of senescent T cells and altered monocyte phenotype/function. However, the most critical similarity between HIV+ individuals and the elderly, which most likely underpins the heightened risk of non-communicable diseases, is chronic inflammation and associated immune activation. Here, we review the similarities between HIV+ individuals and the aged regarding the pathogenesis of inflammatory diseases, the current evidence for mechanisms driving these processes and discuss current and potential therapeutic strategies for addressing inflammatory co-morbidity in HIV+ infection.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Deeks SG, Tracy R, Douek DC. Systemic Effects of Inflammation on Health during Chronic HIV Infection. Immunity. 2013;39:633–45.

    CAS  PubMed  Google Scholar 

  2. 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.

    CAS  PubMed  Google Scholar 

  3. Hearps AC, Maisa A, Cheng WJ, et al. HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy. AIDS. 2012;26:843–53.

    CAS  PubMed  Google Scholar 

  4. French MA, King MS, Tschampa JM, da Silva BA, Landay 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;200:1212–5.

    CAS  PubMed  Google Scholar 

  5. Burdo TH, Lentz MR, Autissier P, et al. Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. J Infect Dis. 2011;204:154–63.

    CAS  PubMed  Google Scholar 

  6. Bazil V, Strominger JL. Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes. J Immunol. 1991;147:1567–74.

    CAS  PubMed  Google Scholar 

  7. Murr C, Widner B, Wirleitner B, Fuchs D. Neopterin as a marker for immune system activation. Curr Drug Metab. 2002;3:175–87.

    CAS  PubMed  Google Scholar 

  8. Neville LF, Mathiak G, Bagasra O. The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. Cytokine Growth Factor Rev. 1997;8:207–19.

    CAS  PubMed  Google Scholar 

  9. Kowal K, Silver R, Slawinska E, et al. CD163 and its role in inflammation. Folia Histochem Cytobiol. 2011;49:365–74.

    CAS  PubMed  Google Scholar 

  10. Hart DN. Dendritic cells: unique leukocyte populations which control the primary immune response. Blood. 1997;90:3245–87.

    CAS  PubMed  Google Scholar 

  11. Lundahl J, Hallden G, Skold CM. Human blood monocytes, but not alveolar macrophages, reveal increased CD11b/CD18 expression and adhesion properties upon receptor-dependent activation. Eur Respir J. 1996;9:1188–94.

    CAS  PubMed  Google Scholar 

  12. Islam FM, Wu J, Jansson J, Wilson DP. Relative risk of cardiovascular disease among people living with HIV: a systematic review and meta-analysis. HIV Med. 2012;13:453–68.

    CAS  PubMed  Google Scholar 

  13. Friis-Moller N, Thiebaut R, Reiss P, et al. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil. 2010;17:491–501.

    PubMed  Google Scholar 

  14. 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.

    CAS  PubMed Central  PubMed  Google Scholar 

  15. 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 multi-cohort collaboration. Lancet. 2008;371:1417–26.

    CAS  PubMed  Google Scholar 

  16. group SIsgaDADs. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS. 2008;22:F17–24.

    Google Scholar 

  17. Worm SW, Sabin C, Weber R, et al. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis. 2010;201:318–30.

    CAS  PubMed  Google Scholar 

  18. Ribaudo HJ, Benson CA, Zheng Y, et al. No risk of myocardial infarction associated with initial antiretroviral treatment containing abacavir: short and long-term results from ACTG A5001/ALLRT. Clin Infect Dis. 2011;52:929–40.

    CAS  PubMed  Google Scholar 

  19. Ding X, Andraca-Carrera E, Cooper C, et al. No association of abacavir use with myocardial infarction: findings of an FDA meta-analysis. J Acquir Immune Defic Syndr. 2012;61:441–7.

    CAS  PubMed  Google Scholar 

  20. Danesh J, Kaptoge S, Mann AG, et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med. 2008;5:e78.

    PubMed Central  PubMed  Google Scholar 

  21. Ridker PM. High-Sensitivity C-Reactive Protein: Potential Adjunct for Global Risk Assessment in the Primary Prevention of Cardiovascular Disease. Circulation. 2001;103:1813–8.

    CAS  PubMed  Google Scholar 

  22. Jenny NS, French B, Arnold AM, et al. Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars. J Gerontol A Biol Sci Med Sci. 2012;67:970–6.

    PubMed  Google Scholar 

  23. El-Sadr WM, Lundgren J, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283–96.

    CAS  PubMed  Google Scholar 

  24. Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5:e203.

    PubMed Central  PubMed  Google Scholar 

  25. Duprez DA, Neuhaus J, Kuller LH, et al. Inflammation, coagulation and cardiovascular disease in HIV-infected individuals. PLoS One. 2012;7:e44454. This large-scale analysis of cardiovascular events in the SMART study demonstrated that the inflammatory markers IL-6, D-dimer and hsCRP confer an increased risk of cardiovascular events amongst treated, HIV infected individuals, independent of other risk factors. This important finding provides evidence for the role of inflammation in the development of non-AIDS comorbidities in HIV infected individuals.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Subramanian S, Tawakol A, Burdo TH, et al. Arterial inflammation in patients with HIV. JAMA. 2012;308:379–86. This study demonstrates that HIV infected individuals have higher levels of arterial wall inflammation compared to controls matched for other cardiovascular risk factors, implicating inflammation as a plausible mechanism for the increased cardiovascular risk conferred by HIV infection.

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Fernandez-Sender L, Alonso-Villaverde C, Rull A, et al. A possible role for CCR5 in the progression of atherosclerosis in HIV-infected patients: a cross-sectional study. AIDS Res Ther. 2013;10:11.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Cipriani S, Francisci D, Mencarelli A, et al. Efficacy of the CCR5 antagonist maraviroc in reducing early, ritonavir-induced atherogenesis and advanced plaque progression in mice. Circulation. 2013;127:2114–24.

    CAS  PubMed  Google Scholar 

  29. Wilkin TJ, Lalama CM, McKinnon J, et al. A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4(+) T-cell recovery despite sustained virologic suppression: ACTG A5256. J Infect Dis. 2012;206:534–42.

    CAS  PubMed  Google Scholar 

  30. Hunt PW, Shulman NS, Hayes TL, et al. The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial. Blood. 2013;121:4635–46.

    CAS  PubMed  Google Scholar 

  31. Crowe SM, Westhorpe CL, Mukhamedova N, et al. The macrophage: the intersection between HIV infection and atherosclerosis. J Leukoc Biol. 2010;87:589–98.

    CAS  PubMed  Google Scholar 

  32. Fitch KV, Srinivasa S, Abbara S, et al. Noncalcified Coronary Atherosclerotic Plaque and Immune Activation in HIV-infected Women. J Infect Dis. 2013;208:1737–46.

    PubMed  Google Scholar 

  33. Funderburg NT, Zidar DA, Shive C, et al. Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome. Blood. 2012;120:4599–608.

    CAS  PubMed  Google Scholar 

  34. Martin GE, Gouillou M, Hearps AC, et al. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women. PLoS One. 2013;8:e55279.

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Hearps AC, Martin GE, Angelovich TA, et al. Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell. 2012;11:867–75.

    CAS  PubMed  Google Scholar 

  36. Nyugen J, Agrawal S, Gollapudi S, Gupta S. Impaired functions of peripheral blood monocyte subpopulations in aged humans. J Clin Immunol. 2010;30:806–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Seidler S, Zimmermann HW, Bartneck M, Trautwein C, Tacke F. Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults. BMC Immunol. 2010;11:30.

    PubMed Central  PubMed  Google Scholar 

  38. Rogacev KS, Cremers B, Zawada AM, et al. CD14++CD16+ Monocytes Independently Predict Cardiovascular Events: A Cohort Study of 951 Patients Referred for Elective Coronary Angiography. J Am Coll Cardiol. 2012;60:1512–20.

    CAS  PubMed  Google Scholar 

  39. Dopheide JF, Obst V, Doppler C, et al. Phenotypic characterisation of pro-inflammatory monocytes and dendritic cells in peripheral arterial disease. Thromb Haemost. 2012;108:1198–207.

    PubMed  Google Scholar 

  40. Burdo TH, Lo J, Abbara S, et al. Soluble CD163, a Novel Marker of Activated Macrophages, Is Elevated and Associated With Noncalcified Coronary Plaque in HIV-Infected Patients. J Infect Dis. 2011;204:1227–36.

    CAS  PubMed  Google Scholar 

  41. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. Aids. 2006;20:2165–74.

    PubMed  Google Scholar 

  42. Triant VA, Brown TT, Lee H, Grinspoon SK. Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab. 2008;93:3499–504.

    CAS  PubMed  Google Scholar 

  43. Torti C, Mazziotti G, Soldini PA, et al. High prevalence of radiological vertebral fractures in HIV-infected males. Endocrine. 2012;41:512–7.

    CAS  PubMed  Google Scholar 

  44. Yin MT, Zhang CA, McMahon DJ, et al. Higher rates of bone loss in postmenopausal HIV-infected women: a longitudinal study. J Clin Endocrinol Metab. 2012;97:554–62.

    CAS  PubMed  Google Scholar 

  45. Pinzone MR, Di Rosa M, Malaguarnera M, et al. Vitamin D deficiency in HIV infection: an underestimated and undertreated epidemic. Eur Rev Med Pharmacol Sci. 2013;17:1218–32.

    CAS  PubMed  Google Scholar 

  46. Ofotokun I, McIntosh E, Weitzmann MN. HIV: inflammation and bone. Curr HIV/AIDS Rep. 2012;9:16–25.

    PubMed Central  PubMed  Google Scholar 

  47. Zupan J, Jeras M, Marc J. Osteoimmunology and the influence of pro-inflammatory cytokines on osteoclasts. Biochem Med (Zagreb). 2013;23:43–63.

    CAS  Google Scholar 

  48. de Pablo P, Cooper MS, Buckley CD. Association between bone mineral density and C-reactive protein in a large population-based sample. Arthritis Rheum. 2012;64:2624–31. A large study investigating the realtionship between hs-CRP levels and BMD in a cohort of 10,475 individuals. hsCRP levels were significantly and inversely associated with BMD after adjustment for a range of demographic and lifestyle factors including age, poverty, menopause, body mass index, smoking, co-morbidities etc. The large particiant numbers and extensive adjustment for confounders provide strong evidence for a link between inflammation and reduecd BMD.

    PubMed  Google Scholar 

  49. Eriksson AL, Moverare-Skrtic S, Ljunggren O, et al.: High sensitive CRP is an independent risk factor for all fractures and vertebral fractures in elderly men: The MrOS Sweden study. J Bone Miner Res. 2013. doi:10.1002/jbmr.2037.

  50. Zou W, Bar-Shavit Z. Dual modulation of osteoclast differentiation by lipopolysaccharide. J Bone Miner Res. 2002;17:1211–8.

    CAS  PubMed  Google Scholar 

  51. Matuszewska A, Szechinski J. Evaluation of selected bone metabolism markers in rheumatoid arthritis patients. Adv Clin Exp Med. 2013;22:193–202.

    PubMed  Google Scholar 

  52. Ghishan FK, Kiela PR. Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases. Am J Physiol Gastrointest Liver Physiol. 2011;300:G191–201.

    CAS  PubMed  Google Scholar 

  53. Merlotti D, Gennari L, Dotta F, Lauro D, Nuti R. Mechanisms of impaired bone strength in type 1 and 2 diabetes. Nutr Metab Cardiovasc Dis. 2010;20:683–90.

    CAS  PubMed  Google Scholar 

  54. Lin JC, Hsieh TY, Wu CC, et al. Association between chronic hepatitis C virus infection and bone mineral density. Calcif Tissue Int. 2012;91:423–9.

    CAS  PubMed  Google Scholar 

  55. Vikulina T, Fan X, Yamaguchi M, et al. Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats. Proc Natl Acad Sci U S A. 2010;107:13848–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Walker Harris V, Brown TT. Bone loss in the HIV-infected patient: evidence, clinical implications, and treatment strategies. J Infect Dis. 2012;205 Suppl 3:S391–8.

    CAS  PubMed  Google Scholar 

  57. Hoy J. Bone, fracture and frailty. Curr Opin HIV AIDS. 2011;6:309–14.

    PubMed  Google Scholar 

  58. Gazzola L, Bellistri GM, Tincati C, et al. Association between peripheral T-Lymphocyte activation and impaired bone mineral density in HIV-infected patients. J Transl Med. 2013;11:51.

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Marchetti G, Tincati C, Silvestri G. Microbial Translocation in the Pathogenesis of HIV Infection and AIDS. Clin Microbiol Rev. 2013;26:2–18.

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Sandler NG, Wand H, Roque A, et al. Plasma Levels of Soluble CD14 Independently Predict Mortality in HIV Infection. J Infect Dis. 2011;203:780–90.

    CAS  PubMed  Google Scholar 

  61. Rajasuriar R, Booth D, Solomon A, et al. Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor alpha and microbial translocation. J Infect Dis. 2010;202:1254–64.

    CAS  PubMed  Google Scholar 

  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;199:1177–85.

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Kitchens RL, Thompson PA. Modulatory effects of sCD14 and LBP on LPS-host cell interactions. J Endotoxin Res. 2005;11:225–9.

    CAS  PubMed  Google Scholar 

  64. Reiner AP, Lange EM, Jenny NS, et al. Soluble CD14: Genomewide Association Analysis and Relationship to Cardiovascular Risk and Mortality in Older Adults. Arterioscler Thromb Vasc Biol. 2013;33:158–64. This study provides strong evidence for sCD14 as an independent predictor of cardiovascular events in previously healthy, aged individuals. The long-term follow up and large study size make this the strongest evidence linking sCD14 to cardiovascular disease in any population.

    CAS  PubMed  Google Scholar 

  65. Romero-Sanchez M, Gonzalez-Serna A, Pacheco YM, et al. Different biological significance of sCD14 and LPS in HIV-infection: importance of the immunovirology stage and association with HIV-disease progression markers. J Infect. 2012;65:431–8.

    PubMed  Google Scholar 

  66. Reus S, Portilla J, Sanchez-Paya J, et al. Low-level HIV viremia is associated with microbial translocation and inflammation. J Acquir Immune Defic Syndr. 2013;62:129–34.

    PubMed  Google Scholar 

  67. Méndez-Lagares G, Romero-Sánchez MC, Ruiz-Mateos E, et al. Long-term suppressive combined antiretroviral treatment does not normalize serum sCD14 levels. J Infect Dis. 2013;207(8):1221–5.

    PubMed  Google Scholar 

  68. Ancuta P, Kamat A, Kunstman KJ, et al. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One. 2008;3:e2516.

    PubMed Central  PubMed  Google Scholar 

  69. Kelesidis T, Kendall MA, Yang OO, Hodis HN, Currier JS. Biomarkers of microbial translocation and macrophage activation: association with progression of subclinical atherosclerosis in HIV-1 infection. J Infect Dis. 2012;206:1558–67.

    CAS  PubMed  Google Scholar 

  70. Marchetti G, Cozzi-Lepri A, Merlini E, et al. Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4+ cell count. Aids. 2011;25:1385–94.

    CAS  PubMed  Google Scholar 

  71. Blodget E, Shen C, Aldrovandi G, et al. Relationship between microbial translocation and endothelial function in HIV infected patients. PLoS ONE. 2012;7:e42624. Electronic Resource.

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Pedersen KK, Pedersen M, Troseid M, et al. Microbial Translocation in HIV Infection is Associated with Dyslipidemia, Insulin Resistance, and Risk of Myocardial Infarction. J Acquir Immune Defic Syndr. 2013;64:425–33.

    CAS  PubMed  Google Scholar 

  73. Manner IW, Baekken M, Kvale D, et al. Markers of microbial translocation predict hypertension in HIV-infected individuals. HIV Med. 2013;14:354–61.

    CAS  PubMed  Google Scholar 

  74. Balagopal A, Gama L, Franco V, et al. Detection of microbial translocation in HIV and SIV infection using the Limulus amebocyte lysate assay is masked by serum and plasma. PLoS ONE. 2012;7:e41258. Electronic Resource.

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Hurley JC. Endotoxemia: methods of detection and clinical correlates. Clin Microbiol Rev. 1995;8:268–92.

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Nilsson PM, Tufvesson H, Leosdottir M, and Melander O: Telomeres and cardiovascular disease risk: an update 2013. Transl Res. 2013;162:371–80.

    Google Scholar 

  77. Kong CM, Lee XW, Wang X. Telomere shortening in human diseases. FEBS J. 2013;280:3180–93.

    CAS  PubMed  Google Scholar 

  78. Weischer M, Bojesen SE, Cawthon RM, et al. Short telomere length, myocardial infarction, ischemic heart disease, and early death. Arterioscler Thromb Vasc Biol. 2012;32:822–9.

    CAS  PubMed  Google Scholar 

  79. Willeit P, Willeit J, Brandstatter A, et al. Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arterioscler Thromb Vasc Biol. 2010;30:1649–56.

    CAS  PubMed  Google Scholar 

  80. Sanders JL, Fitzpatrick AL, Boudreau RM, et al. Leukocyte telomere length is associated with noninvasively measured age-related disease: The Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci. 2012;67:409–16.

    PubMed  Google Scholar 

  81. Fitzpatrick AL, Kronmal RA, Gardner JP, et al. Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am J Epidemiol. 2007;165:14–21.

    PubMed  Google Scholar 

  82. Effros RB, Allsopp R, Chiu CP, et al.: Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. AIDS. 1996;10:F17–22.

    Google Scholar 

  83. Effros RB, Dagarag M, Spaulding C, Man J. The role of CD8+ T-cell replicative senescence in human aging. Immunol Rev. 2005;205:147–57.

    CAS  PubMed  Google Scholar 

  84. Ballon G, Ometto L, Righetti E, et al. Human immunodeficiency virus type 1 modulates telomerase activity in peripheral blood lymphocytes. J Infect Dis. 2001;183:417–24.

    CAS  PubMed  Google Scholar 

  85. Reynoso R, Laufer N, Bolcic F, Quarleri J. Telomerase activity in peripheral blood mononuclear cells from HIV and HIV-HCV coinfected patients. Virus Res. 2010;147:284–7.

    CAS  PubMed  Google Scholar 

  86. Leeansyah E, Cameron PU, Solomon A, et al. Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging. J Infect Dis. 2013;207:1157–65.

    CAS  PubMed  Google Scholar 

  87. Bollmann FM. Telomerase inhibition may contribute to accelerated mitochondrial aging induced by anti-retroviral HIV treatment. Med Hypotheses. 2013;81:285–7.

    CAS  PubMed  Google Scholar 

  88. Comandini A, Naro C, Adamo R, et al. Molecular mechanisms involved in HIV-1-Tat mediated inhibition of telomerase activity in human CD4(+) T lymphocytes. Mol Immunol. 2013;54:181–92.

    CAS  PubMed  Google Scholar 

  89. Wang X, Singh S, Jung HY, et al. HIV-1 Vpr protein inhibits telomerase activity via the EDD-DDB1-VPRBP E3 ligase complex. J Biol Chem. 2013;288:15474–80.

    CAS  PubMed  Google Scholar 

  90. Di Mitri D, Azevedo RI, Henson SM, et al. Reversible senescence in human CD4 + CD45RA + CD27- memory T cells. J Immunol. 2011;187:2093–100.

    PubMed  Google Scholar 

  91. Parish ST, Wu JE, Effros RB. Modulation of T lymphocyte replicative senescence via TNF-{alpha} inhibition: role of caspase-3. J Immunol. 2009;182:4237–43.

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Ouyang Q, Wagner WM, Wikby A, et al. Large numbers of dysfunctional CD8+ T lymphocytes bearing receptors for a single dominant CMV epitope in the very old. J Clin Immunol. 2003;23:247–57.

    CAS  PubMed  Google Scholar 

  93. Derhovanessian E, Maier AB, Hahnel K, et al. Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of late-differentiated CD4+ and CD8+ T-cells in humans. J Gen Virol. 2011;92:2746–56. This analysis of the effect of CMV and herpes simplex virus on T cell subsets in the aged demostrated that the expansion of CD28- memory T cells and ‘senescent’ CD57+ CD8+ T cells previously thought to be due to ageing is only seen in CMV seropositive individuals. This highlights the important roel CMV plays in immunosenescence and the need to adjust for CMV status, and ideally CMV reactivation, in studies of immune activation and ageing.

    CAS  PubMed  Google Scholar 

  94. Chidrawar S, Khan N, Wei W, et al. Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals. Clin Exp Immunol. 2009;155:423–32.

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Solana R, Tarazona R, Aiello AE, et al. CMV and Immunosenescence: from basics to clinics. Immun Ageing. 2012;9:23.

    PubMed Central  PubMed  Google Scholar 

  96. Simanek AM, Dowd JB, Pawelec G, et al. Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States. PLoS ONE. 2011;6:e16103.

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Muhlestein JB, Horne BD, Carlquist JF, et al. Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease. Circulation. 2000;102:1917–23.

    CAS  PubMed  Google Scholar 

  98. 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.

    PubMed Central  PubMed  Google Scholar 

  99. Gianella S, Morris SR, Tatro E, et al.: Virologic Correlates of Anti-CMV IgG Levels in HIV-1 Infected Men. J Infect Dis. 2013. doi:10.1093/infdis/jit434.

  100. Parrinello CM, Sinclair E, Landay AL, et al. Cytomegalovirus immunoglobulin G antibody is associated with subclinical carotid artery disease among HIV-infected women. J Infect Dis. 2012;205:1788–96.

    CAS  PubMed  Google Scholar 

  101. Hsue PY, Hunt PW, Sinclair E, et al. Increased carotid intima-media thickness in HIV patients is associated with increased cytomegalovirus-specific T-cell responses. AIDS. 2006;20:2275–83.

    PubMed  Google Scholar 

  102. Durier N, Ananworanich J, Apornpong T, et al. Cytomegalovirus viremia in Thai HIV-infected patients on antiretroviral therapy: prevalence and associated mortality. Clin Infect Dis. 2013;57:147–55.

    CAS  PubMed  Google Scholar 

  103. 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.

    CAS  PubMed  Google Scholar 

  104. van Baarle D, Tsegaye A, Miedema F, Akbar A. Significance of senescence for virus-specific memory T cell responses: rapid ageing during chronic stimulation of the immune system. Immunol Lett. 2005;97:19–29.

    PubMed  Google Scholar 

  105. Davalos AR, Coppe JP, Campisi J, Desprez PY. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev. 2010;29:273–83.

    PubMed Central  PubMed  Google Scholar 

  106. Deeks SG, Verdin E, McCune JM. Immunosenescence and HIV. Curr Opin Immunol. 2012;24:501–6.

    CAS  PubMed  Google Scholar 

  107. Kaplan RC, Sinclair E, Landay AL, et al. T cell activation and senescence predict subclinical carotid artery disease in HIV-infected women. J Infect Dis. 2011;203:452–63.

    CAS  PubMed  Google Scholar 

  108. Kaplan RC, Sinclair E, Landay AL, et al. T cell activation predicts carotid artery stiffness among HIV-infected women. Atherosclerosis. 2011;217:207–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  109. 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.

    PubMed  Google Scholar 

  110. 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;24:1509–17.

    PubMed Central  PubMed  Google Scholar 

  111. Baker J, Huppler Hullsiek K, and Singh A, Monocyte Activation, but Not T Cell Activation, Predicts Progression of Coronary Artery Calcium in a Contemporary HIV Cohort (Abstract 66LB), in 20th Conference on Retroviruses and Opportunistic Infections 2013: Atlanta, GA, USA.

  112. Tenorio A, Zheng E, and Bosch R, Soluble Markers of Inflammation and Coagulation, but Not T Cell Activation, Predict Non-AIDS-defining Events during Suppressive ART (Abstract 790), in 20th Conference on Retroviruses and Opportunistic Infections2013: Atlanta, GA, USA.

  113. Unemori P, Leslie KS, Hunt PW, et al. Immunosenescence is associated with presence of Kaposi's sarcoma in antiretroviral treated HIV infection. AIDS. 2013;27:1735–42.

    CAS  PubMed  Google Scholar 

  114. Lichtenstein K, Armon C, Buchacz K, et al. Low CD4+ T Cell Count Is a Risk Factor for Cardiovascular Disease Events in the HIV Outpatient Study. Clin Infect Dis. 2010;51:435–47.

    CAS  PubMed  Google Scholar 

  115. Prosperi MC, Cozzi-Lepri A, Castagna A, et al. Incidence of malignancies in HIV-infected patients and prognostic role of current CD4 cell count: evidence from a large Italian cohort study. Clin Infect Dis. 2010;50:1316–21.

    CAS  PubMed  Google Scholar 

  116. Onen NF, Agbebi A, Shacham E, et al. Frailty among HIV-infected persons in an urban outpatient care setting. J Infect. 2009;59:346–52.

    PubMed  Google Scholar 

  117. Pathai S, Gilbert C, Weiss HA, et al. Frailty in HIV-infected adults in South Africa. J Acquir Immune Defic Syndr. 2013;62:43–51.

    PubMed Central  PubMed  Google Scholar 

  118. Yong MK, Elliott JH, Woolley IJ, Hoy JF. Low CD4 count is associated with an increased risk of fragility fracture in HIV-infected patients. J Acquir Immune Defic Syndr. 2011;57:205–10.

    PubMed  Google Scholar 

  119. Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011;53:1120–6.

    PubMed  Google Scholar 

  120. Hasse B, Ledergerber B, Furrer H, et al. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis. 2011;53:1130–9.

    PubMed  Google Scholar 

  121. Galli L, Salpietro S, Pellicciotta G, et al. Risk of type 2 diabetes among HIV-infected and healthy subjects in Italy. Eur J Epidemiol. 2012;27:657–65.

    PubMed  Google Scholar 

  122. Malaza A, Mossong J, Barnighausen T, Newell ML. Hypertension and obesity in adults living in a high HIV prevalence rural area in South Africa. PLoS ONE. 2012;7:e47761.

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Wand H, Ramjee G. High prevalence of obesity among women who enrolled in HIV prevention trials in KwaZulu-Natal, South Africa: healthy diet and life style messages should be integrated into HIV prevention programs. BMC Public Health. 2013;13:159.

    PubMed Central  PubMed  Google Scholar 

  124. Ramachandran A, Snehalatha C. Rising burden of obesity in Asia. J Obes. 2010(2010).

  125. Tian S, Dong GH, Wang D, et al. Factors associated with prevalence, awareness, treatment and control of hypertension in urban adults from 33 communities in China: the CHPSNE Study. Hypertens Res. 2011;34:1087–92.

    PubMed  Google Scholar 

  126. Kengne AP, Echouffo-Tcheugui JB, Sobngwi E, Mbanya JC. New insights on diabetes mellitus and obesity in Africa-part 1: prevalence, pathogenesis and comorbidities. Heart. 2013;99:979–83.

    PubMed  Google Scholar 

  127. Hunter DJ, Reddy KS. Noncommunicable diseases. N Engl J Med. 2013;369:1336–43.

    CAS  PubMed  Google Scholar 

  128. Tang S, Ehiri J, Long Q. China's biggest, most neglected health challenge: Non-communicable diseases. Infect Dis Poverty. 2013;2:7.

    PubMed Central  PubMed  Google Scholar 

  129. Hamill MM, Ward KA, Pettifor JM, Norris SA, and Prentice A: Bone mass, body composition and vitamin D status of ARV-naive, urban, black South African women with HIV infection, stratified by CD count. Osteoporos Int. 2013;24:2855–61.

    Google Scholar 

  130. Muronya W, Sanga E, Talama G, Kumwenda JJ, van Oosterhout JJ. Cardiovascular risk factors in adult Malawians on long-term antiretroviral therapy. Trans R Soc Trop Med Hyg. 2011;105:644–9.

    PubMed  Google Scholar 

  131. Mateen FJ, Kanters S, Kalyesubula R, et al. Hypertension prevalence and Framingham risk score stratification in a large HIV-positive cohort in Uganda. J Hypertens. 2013;31:1372–8. discussion 1378.

    CAS  PubMed  Google Scholar 

  132. Bloomfield GS, Hogan JW, Keter A, et al. Hypertension and obesity as cardiovascular risk factors among HIV seropositive patients in Western Kenya. PLoS ONE. 2011;6:e22288.

    CAS  PubMed Central  PubMed  Google Scholar 

  133. Tsai MS, Hung CC, Liu WC, et al. Reduced bone mineral density among HIV-infected patients in Taiwan: prevalence and associated factors. J Microbiol Immunol Infect. 2012. doi:10.1016/j.jmii.2012.08.026.

    Google Scholar 

  134. Erlandson KM, Allshouse AA, Jankowski CM, et al. Association of functional impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy. J Infect Dis. 2013;208:249–59.

    CAS  PubMed  Google Scholar 

  135. Appay V, Fastenackels S, Katlama C, et al. Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patients. AIDS. 2011;25:1813–22.

    CAS  PubMed  Google Scholar 

  136. Masia M, Robledano C. Ortiz de la Tabla V, et al.: Increased carotid intima-media thickness associated with antibody responses to varicella-zoster virus and cytomegalovirus in HIV-infected patients. PLoS ONE. 2013;8:e64327.

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Cassol E, Malfeld S, Mahasha P, et al. Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy. J Infect Dis. 2010;202:723–33.

    CAS  PubMed  Google Scholar 

  138. Ledwaba L, Tavel JA, Khabo 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.

    CAS  PubMed Central  PubMed  Google Scholar 

  139. Ford N, Shubber Z, Saranchuk P, et al.: Burden of HIV-Related Cytomegalovirus Retinitis in Resource-Limited Settings: A Systematic Review. Clin Infect Dis. 2013;57:1351–61.

    Google Scholar 

  140. Nakanjako D, Ssewanyana I, Nabatanzi R, et al. Impaired T-cell proliferation among HAART-treated adults with suboptimal CD4 recovery in an African cohort. BMC Immunol. 2013;14:26.

    CAS  PubMed Central  PubMed  Google Scholar 

  141. Hunt PW, Cao HL, Muzoora C, et al. Impact of CD8+ T-cell activation on CD4+ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. AIDS. 2011;25:2123–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  142. Shiels PG, McGlynn LM, MacIntyre A, et al. Accelerated telomere attrition is associated with relative household income, diet and inflammation in the pSoBid cohort. PLoS ONE. 2011;6:e22521.

    CAS  PubMed Central  PubMed  Google Scholar 

  143. Atun R, Jaffar S, Nishtar S, et al. Improving responsiveness of health systems to non-communicable diseases. Lancet. 2013;381:690–7.

    PubMed  Google Scholar 

  144. Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013;382:1525–33.

    PubMed  Google Scholar 

  145. Nelson MR, Reid CM, Ames DA, et al. Feasibility of conducting a primary prevention trial of low-dose aspirin for major adverse cardiovascular events in older people in Australia: results from the ASPirin in Reducing Events in the Elderly (ASPREE) pilot study. Med J Aust. 2008;189:105–9.

    PubMed  Google Scholar 

  146. O'Brien M, Montenont E, Hu L, et al. Aspirin attenuates platelet activation and immune activation in HIV-infected subjects on antiretroviral therapy: A Pilot Study. J Acquir Immune Defic Syndr. 2013;63:280–8. Reporting the striking finding of significantly reduced T cell actiavtion and sCD14 levels in virologically suppressed HIV+ individuals after only 1 week of treatment with aspirin. Although only a small study (25 HIV+ and 45 control participants), the data highlight the significant activation of platlets in HIV infection and the influence this has on monocyte activation and thus inflammation/immune activation. This is to date a poorly investigated area in HIV infection.

    PubMed  Google Scholar 

  147. Antonopoulos AS, Margaritis M, Lee R, Channon K, Antoniades C. Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials. Curr Pharm Des. 2012;18:1519–30.

    CAS  PubMed Central  PubMed  Google Scholar 

  148. Calza L, Trapani F, Bartoletti M, et al. Statin Therapy Decreases Serum Levels of High-Sensitivity C-Reactive Protein and Tumor Necrosis Factor-α in HIV-Infected Patients Treated With Ritonavir-Boosted Protease Inhibitors. HIV Clinical Trials. 2012;13:153–61.

    CAS  PubMed  Google Scholar 

  149. Baker JV, Huppler Hullsiek K, Prosser R, et al. Angiotensin Converting Enzyme Inhibitor and HMG-CoA Reductase Inhibitor as Adjunct Treatment for Persons with HIV Infection: A Feasibility Randomized Trial. PLoS ONE. 2012;7:e46894.

    CAS  PubMed Central  PubMed  Google Scholar 

  150. De Wit S, Delforge M, Necsoi CV, Clumeck N. Downregulation of CD38 activation markers by atorvastatin in HIV patients with undetectable viral load. Aids. 2011;25:1332–3.

    PubMed  Google Scholar 

  151. Fichtenbaum CJ, Yeh TM, Evans SR, Aberg JA. Treatment with pravastatin and fenofibrate improves atherogenic lipid profiles but not inflammatory markers in ACTG 5087. J Clin Lipidol. 2010;4:279–87.

    PubMed Central  PubMed  Google Scholar 

  152. Rasmussen LD, Kronborg G, Larsen CS, et al. Statin Therapy and Mortality in HIV-Infected Individuals; A Danish Nationwide Population-Based Cohort Study. PLoS ONE. 2013;8:e52828.

    CAS  PubMed Central  PubMed  Google Scholar 

  153. Piconi S, Parisotto S, Rizzardini G, et al. Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy–treated immunologic nonresponders. Blood. 2011;118:3263–72.

    CAS  PubMed  Google Scholar 

  154. Murray SM, Down CM, Boulware DR, et al. Reduction of immune activation with chloroquine therapy during chronic HIV infection. J Virol. 2010;84:12082–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  155. Paton Ni GRLDDT et al. Effects of hydroxychloroquine on immune activation and disease progression among hiv-infected patients not receiving antiretroviral therapy: A randomized controlled trial. JAMA. 2012;308:353–61.

    PubMed  Google Scholar 

  156. Cunningham-Rundles S, Ahrne S, Johann-Liang R, et al. Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infection. Nutrients. 2011;3:1042–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  157. Klatt NR, Canary LA, Sun X, et al. Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques. J Clin Invest. 2013;123:903–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  158. Gonzalez-Hernandez LA, Jave-Suarez LF, Fafutis-Morris M, et al. Synbiotic therapy decreases microbial translocation and inflammation and improves immunological status in HIV-infected patients: a double-blind randomized controlled pilot trial. Nutr J. 2012;11:90.

    CAS  PubMed Central  PubMed  Google Scholar 

  159. Schunter M, Chu H, Hayes TL, et al. Randomized pilot trial of a synbiotic dietary supplement in chronic HIV-1 infection. BMC Complement Alternat Med. 2012;12:84.

    Google Scholar 

  160. Lassenius MI, Pietilainen KH, Kaartinen K, et al. Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation. Diabetes Care. 2011;34:1809–15.

    CAS  PubMed  Google Scholar 

  161. Gonzalez-Quintela A, Alonso M, Campos J, et al. Determinants of serum concentrations of lipopolysaccharide-binding protein (LBP) in the adult population: the role of obesity. PLoS One. 2013;8:e54600.

    CAS  PubMed Central  PubMed  Google Scholar 

  162. De Luca A, de Gaetano DK, Colafigli M, et al. The association of high-sensitivity c-reactive protein and other biomarkers with cardiovascular disease in patients treated for HIV: a nested case–control study. BMC Infect Dis. 2013;13:414.

    PubMed Central  PubMed  Google Scholar 

  163. Koethe JR, Dee K, Bian A, et al. Circulating interleukin-6, soluble CD14, and other inflammation biomarker levels differ between obese and nonobese HIV-infected adults on antiretroviral therapy. AIDS Res Hum Retrovir. 2013;29:1019–25.

    CAS  PubMed  Google Scholar 

  164. Hussein AA, Gottdiener JS, Bartz TM, et al. Inflammation and sudden cardiac death in a community-based population of older adults: The Cardiovascular Health Study. Heart Rhythm. 2013;10:1425–32.

    PubMed  Google Scholar 

  165. Empana JP, Jouven X, Canoui-Poitrine F, et al. C-reactive protein, interleukin 6, fibrinogen and risk of sudden death in European middle-aged men: the PRIME study. Arterioscler Thromb Vasc Biol. 2010;30:2047–52.

    CAS  PubMed  Google Scholar 

  166. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101:1767–72.

    CAS  PubMed  Google Scholar 

  167. Jenny NS, Tracy RP, Ogg MS, et al. In the elderly, interleukin-6 plasma levels and the -174G > C polymorphism are associated with the development of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2002;22:2066–71.

    CAS  PubMed  Google Scholar 

  168. Hsue PY, Scherzer R, Hunt PW, et al.: Carotid Intima-Media Thickness Progression in HIV-Infected Adults Occurs Preferentially at the Carotid Bifurcation and Is Predicted by Inflammation. Journal of the American Heart Association. 2012, 1. doi:10.1161/JAHA.111.000422.

  169. Biron A, Bobin-Dubigeon C, Volteau C, et al. Metabolic syndrome in French HIV-infected patients: prevalence and predictive factors after 3 years of antiretroviral therapy. AIDS Res Hum Retrovir. 2012;28:1672–8.

    CAS  PubMed  Google Scholar 

  170. Brown TT, Tassiopoulos K, Bosch RJ, Shikuma C, McComsey GA. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care. 2010;33:2244–9.

    PubMed  Google Scholar 

  171. Schnabel RB, Yin X, Larson MG, et al. Multiple inflammatory biomarkers in relation to cardiovascular events and mortality in the community. Arterioscler Thromb Vasc Biol. 2013;33:1728–33.

    CAS  PubMed  Google Scholar 

  172. Parkner T, Sorensen LP, Nielsen AR, et al. Soluble CD163: a biomarker linking macrophages and insulin resistance. Diabetologia. 2012;55:1856–62.

    CAS  PubMed  Google Scholar 

  173. 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;17:1345–9.

    CAS  PubMed  Google Scholar 

  174. Longenecker C, Funderburg N, Jiang Y, et al.: Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals. HIV Med. 2013;14:385–90.

    Google Scholar 

  175. Merlini E, Luzi K, Suardi E, et al. T-cell phenotypes, apoptosis and inflammation in HIV+ patients on virologically effective cART with early atherosclerosis. PLoS One. 2012;7:e46073.

    CAS  PubMed Central  PubMed  Google Scholar 

  176. Shikuma CM, Barbour JD, Ndhlovu LC, et al.: Plasma Monocyte Chemoattractant Protein-1 and Tumor Necrosis Factor-alpha Levels Predict the Presence of Coronary Artery Calcium in HIV-Infected Individuals Independent of Traditional Cardiovascular Risk Factors. AIDS Res Hum Retroviruses. 2013. doi:10.1089/aid.2013.0183.

  177. Aristoteli LP, Moller HJ, Bailey B, Moestrup SK, Kritharides L. The monocytic lineage specific soluble CD163 is a plasma marker of coronary atherosclerosis. Atherosclerosis. 2006;184:342–7.

    CAS  PubMed  Google Scholar 

  178. Fjeldborg K, Christiansen T, Bennetzen M, et al. The Macrophage-Specific Serum Marker, Soluble CD163, Is Increased in Obesity and Reduced After Dietary-Induced Weight Loss. Obesity. 2013. doi:10.1002/oby.20376. Silver Spring.

    PubMed  Google Scholar 

  179. Zanni MV, Burdo TH. Makimura H, Williams KC, and Grinspoon SK: Relationship between monocyte/macrophage activation marker soluble CD163 and insulin resistance in obese and normal-weight subjects. Clin Endocrinol (Oxf). 2012;77:385–90.

    CAS  Google Scholar 

  180. Moller HJ, Frikke-Schmidt R, Moestrup SK, Nordestgaard BG, Tybjaerg-Hansen A. Serum soluble CD163 predicts risk of type 2 diabetes in the general population. Clin Chem. 2011;57:291–7.

    PubMed  Google Scholar 

  181. Vassallo M, Dunais B, Durant J, et al. Relevance of lipopolysaccharide levels in HIV-associated neurocognitive impairment: the Neuradapt study. J Neurovirol. 2013;19:376–82.

    CAS  PubMed  Google Scholar 

  182. Weaver JD, Huang MH, Albert M, et al. Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology. 2002;59:371–8.

    CAS  PubMed  Google Scholar 

  183. Noble JM, Manly JJ, Schupf N, et al. Association of C-reactive protein with cognitive impairment. Arch Neurol. 2010;67:87–92.

    PubMed  Google Scholar 

  184. Ryan LA, Zheng J, Brester M, et al. Plasma levels of soluble CD14 and tumor necrosis factor-alpha type II receptor correlate with cognitive dysfunction during human immunodeficiency virus type 1 infection. J Infect Dis. 2001;184:699–706.

    CAS  PubMed  Google Scholar 

  185. Kamat A, Lyons JL, Misra V, et al.: Monocyte Activation Markers in Cerebrospinal Fluid Associated With Impaired Neurocognitive Testing in Advanced HIV Infection. J Acquir Immune Defic Syndr 2012, 60:234–243 10.

    Google Scholar 

  186. Lyons JL, Uno H, Ancuta P, et al.: Plasma sCD14 Is a Biomarker Associated With Impaired Neurocognitive Test Performance in Attention and Learning Domains in HIV Infection. J Acquir Immune Defic Syndr 2011, 57:371–379 10.

    Google Scholar 

  187. Engelhart MJ, Geerlings MI, Meijer J, et al. Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol. 2004;61:668–72.

    PubMed  Google Scholar 

  188. Bruunsgaard H, Andersen-Ranberg K, Jeune B, et al. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci. 1999;54:M357–64.

    CAS  PubMed  Google Scholar 

  189. Burdo TH, Weiffenbach A, Woods SP, et al. Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection. Aids. 2013;27:1387–95.

    CAS  PubMed  Google Scholar 

  190. Blasko I, Knaus G, Weiss E, et al. Cognitive deterioration in Alzheimer's disease is accompanied by increase of plasma neopterin. J Psychiatr Res. 2007;41:694–701.

    PubMed  Google Scholar 

  191. Marks MA, Rabkin CS, Engels EA, et al. Markers of microbial translocation and risk of AIDS-related lymphoma. AIDS. 2013;27:469–74.

    CAS  PubMed  Google Scholar 

  192. Borges AH, Silverberg MJ, Wentworth D, et al. Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers. Aids. 2013;27:1433–41.

    CAS  PubMed  Google Scholar 

  193. Il'yasova D, Colbert LH, Harris TB, et al. Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomarkers Prev. 2005;14:2413–8.

    PubMed  Google Scholar 

  194. Ding C, Parameswaran V, Udayan R, Burgess J, Jones G. Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J Clin Endocrinol Metab. 2008;93:1952–8.

    CAS  PubMed  Google Scholar 

  195. Scheidt-Nave C, Bismar H, Leidig-Bruckner G, et al. Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause. J Clin Endocrinol Metab. 2001;86:2032–42.

    CAS  PubMed  Google Scholar 

  196. Margolick J, Jacobson L, and Lopez J, Frailty and circulating concentrations of proinflammatory cytokines and chemokines in HIV-infected and -uninfected men in the Multicenter AIDS Cohort Study (MACS). , in 3rd International Workshop on HIV and Aging. 2012: Baltimore, USA.

  197. Ferrucci L, Harris TB, Guralnik JM, et al. Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc. 1999;47:639–46.

    CAS  PubMed  Google Scholar 

  198. Walston J, McBurnie MA, Newman A, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med. 2002;162:2333–41.

    PubMed  Google Scholar 

  199. Leng SX, Tian X, Matteini A, et al. IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age Ageing. 2011;40:475–81.

    PubMed  Google Scholar 

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Anna C. Hearps, Genevieve E. Martin, Reena Rajasuriar, and Suzanne M. Crowe declare that they have no conflict of interest

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Hearps, A.C., Martin, G.E., Rajasuriar, R. et al. Inflammatory Co-morbidities in HIV+ Individuals: Learning Lessons from Healthy Ageing. Curr HIV/AIDS Rep 11, 20–34 (2014). https://doi.org/10.1007/s11904-013-0190-8

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Keywords

  • HIV co-morbidity
  • Inflammation
  • Immune activation
  • Microbial translocation
  • Monocyte
  • Immune senescence
  • Telomere
  • Resource limited settings
  • Cytomegalovirus
  • HIV pathogenesis
  • Pathogenesis
  • Treatment
  • HIV+ infection
  • Senescent T cells
  • HIV+ individuals
  • HIV-positive
  • Healthy ageing
  • Co-morbidity