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Journal of Endocrinological Investigation

, Volume 41, Issue 8, pp 881–899 | Cite as

Endocrinological aspects of HIV infection

  • F. S. MirzaEmail author
  • P. Luthra
  • L. Chirch
Review

Abstract

Purpose

Patients with human immunodeficiency virus (HIV) are living longer with effective antiretroviral therapies and are enjoying near normal life span. Therefore, they are encountering endocrine issues faced by the general population along with those specific to HIV infection. The purpose of this article is to review the common endocrine aspects of HIV infection, and the early detection and management strategies for these complications.

Methods

Recent literature on HIV and endocrine disease was reviewed.

Results

HIV can influence endocrine glands at several levels. Endocrine glandular function may be altered by the direct effect of HIV viral proteins, through generation of systemic and local cytokines and the inflammatory response and via glandular involvement with opportunistic infections and HIV-related malignancies. Endocrine disorders seen in people with HIV include metabolic issues related to obesity such as diabetes, hyperlipidemia, lipohypertrophy, lipoatrophy and lipodystrophy and contribute significantly to quality of life, morbidity and mortality. In addition, hypogonadism, osteopenia and osteoporosis are also more prevalent in the patients with HIV. Although disorders of hypothalamic–pituitary–adrenal axis resulting in adrenal insufficiency can be life threatening, these along with thyroid dysfunction are being seen less commonly in the antiretroviral therapy (ART) era. ARTs have greatly improved life expectancy in people living with HIV but can also have adverse endocrine effects.

Conclusions

Clinicians need to have a high index of suspicion for endocrine abnormalities in people with HIV as they can be potentially life threatening if untreated. Endocrine evaluation should be pursued as in the general population, with focus on prevention, early detection and treatment to improve quality of life and longevity.

Keywords

Human immunodeficiency virus Antiretroviral therapy Endocrinopathy Bone disease Lipodystrophy Diabetes Hyperlipidemia 

Notes

Acknowledgements

The authors thank Professor Ernesto Canalis and Ms. Mary Yurczak for their support of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors do not have any disclosures.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

No informed consent.

References

  1. 1.
  2. 2.
    Antiretroviral Therapy Cohort C (2017) Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV 4(8):e349–e356CrossRefGoogle Scholar
  3. 3.
    Brown TT et al (2005) Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med 165(10):1179–1184PubMedCrossRefGoogle Scholar
  4. 4.
    De Wit S et al (2008) 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 31(6):1224–1229PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Rasmussen LD et al (2012) Risk of diabetes mellitus in persons with and without HIV: a Danish nationwide population-based cohort study. PLoS ONE 7(9):e44575PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Polsky S et al (2011) Incident hyperglycaemia among older adults with or at-risk for HIV infection. Antivir Ther 16(2):181–188PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Hernandez-Romieu AC et al (2017) Is diabetes prevalence higher among HIV-infected individuals compared with the general population? Evidence from MMP and NHANES 2009–2010. BMJ Open Diabetes Res Care 5(1):e000304PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Triant VA et al (2007) Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 92(7):2506–2512PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Galli L et al (2012) Risk of type 2 diabetes among HIV-infected and healthy subjects in Italy. Eur J Epidemiol 27(8):657–665PubMedCrossRefGoogle Scholar
  10. 10.
    Howard AA et al (2010) The effects of opiate use and hepatitis C virus infection on risk of diabetes mellitus in the Women’s Interagency HIV Study. J Acquir Immune Defic Syndr 54(2):152–159PubMedPubMedCentralGoogle Scholar
  11. 11.
    Butt AA et al (2009) HIV infection and the risk of diabetes mellitus. AIDS 23(10):1227–1234PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Hadigan C, Kattakuzhy S (2014) Diabetes mellitus type 2 and abnormal glucose metabolism in the setting of human immunodeficiency virus. Endocrinol Metab Clin North Am 43(3):685–696PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Veloso S et al (2012) Leptin and adiponectin, but not IL18, are related with insulin resistance in treated HIV-1-infected patients with lipodystrophy. Cytokine 58(2):253–260PubMedCrossRefGoogle Scholar
  14. 14.
    Vigouroux C et al (2003) Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy. AIDS 17(10):1503–1511PubMedCrossRefGoogle Scholar
  15. 15.
    Palmer CS et al (2016) Regulators of glucose metabolism in CD4+ and CD8+ T Cells. Int Rev Immunol 35(6):477–488PubMedCrossRefGoogle Scholar
  16. 16.
    Butt AA et al (2004) Risk of diabetes in HIV infected veterans pre- and post-HAART and the role of HCV coinfection. Hepatology 40(1):115–119PubMedCrossRefGoogle Scholar
  17. 17.
    Mehta SH et al (2003) The effect of HAART and HCV infection on the development of hyperglycemia among HIV-infected persons. J Acquir Immune Defic Syndr 33(5):577–584PubMedCrossRefGoogle Scholar
  18. 18.
    Monroe AK et al (2011) Sex hormones, insulin resistance, and diabetes mellitus among men with or at risk for HIV infection. J Acquir Immune Defic Syndr 58(2):173–180PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Rotger M et al (2010) Impact of single nucleotide polymorphisms and of clinical risk factors on new-onset diabetes mellitus in HIV-infected individuals. Clin Infect Dis 51(9):1090–1098PubMedCrossRefGoogle Scholar
  20. 20.
    Hruz PW (2011) Molecular mechanisms for insulin resistance in treated HIV-infection. Best Pract Res Clin Endocrinol Metab 25(3):459–468PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Brown TT et al (2005) Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study. Aids 19(13):1375–1383PubMedCrossRefGoogle Scholar
  22. 22.
    Cossarizza A, Moyle G (2004) Antiretroviral nucleoside and nucleotide analogues and mitochondria. AIDS 18(2):137–151PubMedCrossRefGoogle Scholar
  23. 23.
    Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307(5708):384–387PubMedCrossRefGoogle Scholar
  24. 24.
    McComsey GA et al (2005) Improvements in lipoatrophy, mitochondrial DNA levels and fat apoptosis after replacing stavudine with abacavir or zidovudine. AIDS 19(1):15–23PubMedCrossRefGoogle Scholar
  25. 25.
    Venhoff N et al (2007) Mitochondrial toxicity of tenofovir, emtricitabine and abacavir alone and in combination with additional nucleoside reverse transcriptase inhibitors. Antivir Ther 12(7):1075–1085PubMedGoogle Scholar
  26. 26.
    Aberg JA et al (2012) Metabolic effects of darunavir/ritonavir versus atazanavir/ritonavir in treatment-naive, HIV type 1-infected subjects over 48 weeks. AIDS Res Hum Retroviruses 28(10):1184–1195PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Overton ET et al (2016) Effects of once-daily darunavir/ritonavir versus atazanavir/ritonavir on insulin sensitivity in HIV-infected persons over 48 weeks: results of an exploratory substudy of METABOLIK, a phase 4, randomized trial. HIV Clin Trials 17(2):72–77PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Quercia R et al (2015) Comparative changes of lipid levels in treatment-naive, HIV-1-infected adults treated with dolutegravir vs. efavirenz, raltegravir, and ritonavir-boosted darunavir-based regimens over 48 weeks. Clin Drug Investig 35(3):211–219PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Bloomgarden ZT, Handelsman Y (2016) Approaches to treatment 2: comparison of American Association of Clinical Endocrinologists (AACE) and American Diabetes Association (ADA) type 2 diabetes treatment guidelines. J Diabetes 8(1):4–6PubMedCrossRefGoogle Scholar
  30. 30.
    Aberg JA et al (2014) Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 58(1):1–10PubMedCrossRefGoogle Scholar
  31. 31.
    Kim PS et al (2009) A1C underestimates glycemia in HIV infection. Diabetes Care 32(9):1591–1593PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Diop ME et al (2006) Inappropriately low glycated hemoglobin values and hemolysis in HIV-infected patients. AIDS Res Hum Retrovir 22(12):1242–1247PubMedCrossRefGoogle Scholar
  33. 33.
    Polgreen PM, Putz D, Stapleton JT (2003) Inaccurate glycosylated hemoglobin A1C measurements in human immunodeficiency virus-positive patients with diabetes mellitus. Clin Infect Dis 37(4):e53–e56PubMedCrossRefGoogle Scholar
  34. 34.
    Glesby MJ et al (2010) Glycated haemoglobin in diabetic women with and without HIV infection: data from the Women’s Interagency HIV Study. Antivir Ther 15(4):571–577PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Slama L et al (2014) Inaccuracy of haemoglobin A1c among HIV-infected men: effects of CD4 cell count, antiretroviral therapies and haematological parameters. J Antimicrob Chemother 69(12):3360–3367PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Inzucchi SE et al (2012) Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 55(6):1577–1596PubMedCrossRefGoogle Scholar
  37. 37.
    Look ARG et al (2007) Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 30(6):1374–1383CrossRefGoogle Scholar
  38. 38.
    Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed 28 Nov 2016
  39. 39.
    Hajjar J, Habra MA, Naing A (2013) Metformin: an old drug with new potential. Expert Opin Investig Drugs 22(12):1511–1517PubMedCrossRefGoogle Scholar
  40. 40.
    Kohli R et al (2007) A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophy. HIV Med 8(7):420–426PubMedCrossRefGoogle Scholar
  41. 41.
  42. 42.
    Moyle GJ et al (2015) A randomized comparative trial of continued abacavir/lamivudine plus efavirenz or replacement with efavirenz/emtricitabine/tenofovir DF in hypercholesterolemic HIV-1 infected individuals. PLoS ONE 10(2):e0116297PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Mothe B et al (2009) HIV-1 infection in subjects older than 70: a multicenter cross-sectional assessment in Catalonia, Spain. Curr HIV Res 7(6):597–600PubMedCrossRefGoogle Scholar
  44. 44.
    Grinspoon SK et al (2008) State of the science conference: initiative to decrease cardiovascular risk and increase quality of care for patients living with HIV/AIDS: executive summary. Circulation 118(2):198–210PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Grunfeld C et al (1991) Circulating interferon-alpha levels and hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med 90(2):154–162PubMedCrossRefGoogle Scholar
  46. 46.
    Grunfeld C et al (1992) Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab 74(5):1045–1052PubMedGoogle Scholar
  47. 47.
    Husain NE, Ahmed MH (2015) Managing dyslipidemia in HIV/AIDS patients: challenges and solutions. HIV AIDS (Auckl) 7:1–10Google Scholar
  48. 48.
    Calvo M, Martinez E (2014) Update on metabolic issues in HIV patients. Curr Opin HIV AIDS 9(4):332–339PubMedCrossRefGoogle Scholar
  49. 49.
    Calza L et al (2016) Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother 71(6):1451–1465PubMedCrossRefGoogle Scholar
  50. 50.
    Chastain DB, Henderson H, Stover KR (2015) Epidemiology and management of antiretroviral-associated cardiovascular disease. Open AIDS J 9:23–37PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Eron JJ et al (2010) Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet 375(9712):396–407PubMedCrossRefGoogle Scholar
  52. 52.
    Lennox JL et al (2010) Raltegravir versus efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. JAIDS 55(1):39–48PubMedGoogle Scholar
  53. 53.
    Grunfeld C (2010) Dyslipidemia and its treatment in HIV infection. Top HIV Med 18(3):112–118PubMedPubMedCentralGoogle Scholar
  54. 54.
    Mitka M (2015) Exploring statins to decrease HIV-related heart disease risk. JAMA 314(7):657–659PubMedCrossRefGoogle Scholar
  55. 55.
    Nayor M, Vasan RS (2016) Recent update to the US Cholesterol Treatment Guidelines. A comparison with international guidelines. Circulation 133(18):1795–1806PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Aberg JA et al (2014) Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis 58(1):e1–e34PubMedCrossRefGoogle Scholar
  57. 57.
    Lichtenstein KA et al (2003) Incidence of and risk factors for lipoatrophy (abnormal fat loss) in ambulatory HIV-1-infected patients. J Acquir Immune Defic Syndr 32(1):48–56PubMedCrossRefGoogle Scholar
  58. 58.
    Heath KV et al (2001) Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. AIDS 15(2):231–239PubMedCrossRefGoogle Scholar
  59. 59.
    Lo JC et al (1998) Body shape changes in HIV-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol 19(3):307–308PubMedCrossRefGoogle Scholar
  60. 60.
    Leitz G, Robinson P (2000) The development of lipodystrophy on a protease inhibitor-sparing highly active antiretroviral therapy regimen. AIDS 14(4):468–469PubMedCrossRefGoogle Scholar
  61. 61.
    Mynarcik DC et al (2000) Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy. J Acquir Immune Defic Syndr 25(4):312–321PubMedCrossRefGoogle Scholar
  62. 62.
    Wohl D et al (2008) The associations of regional adipose tissue with lipid and lipoprotein levels in HIV-infected men. J Acquir Immune Defic Syndr 48(1):44–52PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Guaraldi G et al (2008) Severity of lipodystrophy is associated with decreased health-related quality of life. AIDS Patient Care STDS 22(7):577–585PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Reynolds NR et al (2006) Balancing disfigurement and fear of disease progression: patient perceptions of HIV body fat redistribution. AIDS Care 18(7):663–673PubMedCrossRefGoogle Scholar
  65. 65.
    Tien PC, Grunfeld C (2004) What is HIV-associated lipodystrophy? Defining fat distribution changes in HIV infection. Curr Opin Infect Dis 17(1):27–32PubMedCrossRefGoogle Scholar
  66. 66.
    Jacobson DL et al (2005) Prevalence of, evolution of, and risk factors for fat atrophy and fat deposition in a cohort of HIV-infected men and women. Clin Infect Dis 40(12):1837–1845PubMedCrossRefGoogle Scholar
  67. 67.
    Lichtenstein KA et al (2001) Clinical assessment of HIV-associated lipodystrophy in an ambulatory population. AIDS 15(11):1389–1398PubMedCrossRefGoogle Scholar
  68. 68.
    Miller J et al (2003) HIV lipodystrophy: prevalence, severity and correlates of risk in Australia. HIV Med 4(3):293–301PubMedCrossRefGoogle Scholar
  69. 69.
    Montes AH et al (2010) The MMP1 (-16071G/2G) single nucleotide polymorphism associates with the HAART-related lipodystrophic syndrome. AIDS 24(16):2499–2506PubMedCrossRefGoogle Scholar
  70. 70.
    Hulgan T et al (2011) European mitochondrial DNA haplogroups and metabolic changes during antiretroviral therapy in AIDS Clinical Trials Group Study A5142. AIDS 25(1):37–47PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Bogner JR et al (2001) Stavudine versus zidovudine and the development of lipodystrophy. J Acquir Immune Defic Syndr 27(3):237–244PubMedCrossRefGoogle Scholar
  72. 72.
    Cherry CL et al (2006) Tissue-specific associations between mitochondrial DNA levels and current treatment status in HIV-infected individuals. J Acquir Immune Defic Syndr 42(4):435–440PubMedCrossRefGoogle Scholar
  73. 73.
    Moyle GJ et al (2006) A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. AIDS 20(16):2043–2050PubMedCrossRefGoogle Scholar
  74. 74.
    Martin A et al (2004) Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study. AIDS 18(7):1029–1036PubMedCrossRefGoogle Scholar
  75. 75.
    Loutfy MR et al (2007) Immediate versus delayed polyalkylimide gel injections to correct facial lipoatrophy in HIV-positive patients. AIDS 21(9):1147–1155PubMedCrossRefGoogle Scholar
  76. 76.
    Moyle GJ et al (2006) Long-term safety and efficacy of poly-l-lactic acid in the treatment of HIV-related facial lipoatrophy. HIV Med 7(3):181–185PubMedCrossRefGoogle Scholar
  77. 77.
    Mulligan K et al (2009) The effects of recombinant human leptin on visceral fat, dyslipidemia, and insulin resistance in patients with human immunodeficiency virus-associated lipoatrophy and hypoleptinemia. J Clin Endocrinol Metab 94(4):1137–1144PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Magkos F et al (2011) Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study. Metabolism 60(7):1045–1049PubMedCrossRefGoogle Scholar
  79. 79.
    Guaraldi G et al (2013) CD8 T-cell activation is associated with lipodystrophy and visceral fat accumulation in antiretroviral therapy-treated virologically suppressed HIV-infected patients. J Acquir Immune Defic Syndr 64(4):360–366PubMedCrossRefGoogle Scholar
  80. 80.
    Damouche A et al (2015) Adipose tissue is a neglected viral reservoir and an inflammatory site during chronic HIV and SIV infection. PLoS Pathog 11(9):e1005153PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Vidal F et al (2012) Adipogenic/lipid, inflammatory, and mitochondrial parameters in subcutaneous adipose tissue of untreated HIV-1-infected long-term nonprogressors: significant alterations despite low viral burden. J Acquir Immune Defic Syndr 61(2):131–137PubMedCrossRefGoogle Scholar
  82. 82.
    Agarwal N, Balasubramanyam A (2015) Viral mechanisms of adipose dysfunction: lessons from HIV-1 Vpr. Adipocyte 4(1):55–59PubMedCrossRefGoogle Scholar
  83. 83.
    Gerard P (2016) Gut microbiota and obesity. Cell Mol Life Sci 73(1):147–162PubMedCrossRefGoogle Scholar
  84. 84.
    Rietschel P et al (2001) Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy. J Clin Endocrinol Metab 86(2):504–510PubMedGoogle Scholar
  85. 85.
    Lake JE, Currier JS (2013) Metabolic disease in HIV infection. Lancet Infect Dis 13(11):964–975PubMedCrossRefGoogle Scholar
  86. 86.
    Caron-Debarle M et al (2010) Adipose tissue as a target of HIV-1 antiretroviral drugs. Potential consequences on metabolic regulations. Curr Pharm Des 16(30):3352–3360PubMedCrossRefGoogle Scholar
  87. 87.
    Dube MP et al (2007) Long-term body fat outcomes in antiretroviral-naive participants randomized to nelfinavir or efavirenz or both plus dual nucleosides. Dual X-ray absorptiometry results from A5005S, a substudy of Adult Clinical Trials Group 384. J Acquir Immune Defic Syndr 45(5):508–514PubMedCrossRefGoogle Scholar
  88. 88.
    Haubrich RH et al (2009) Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment. AIDS 23(9):1109–1118PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Caron-Debarle M et al (2010) HIV-associated lipodystrophy: from fat injury to premature aging. Trends Mol Med 16(5):218–229PubMedCrossRefGoogle Scholar
  90. 90.
    McComsey GA et al (2016) Body composition changes after initiation of raltegravir or protease inhibitors: ACTG A5260S. Clin Infect Dis 62(7):853–862PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Moyle GJ et al (2014) Comparison of body composition changes between atazanavir/ritonavir and lopinavir/ritonavir each in combination with tenofovir/emtricitabine in antiretroviral-naive patients with HIV-1 infection. Clin Drug Investig 34(4):287–296PubMedCrossRefGoogle Scholar
  92. 92.
    Vrouenraets SM et al (2011) Randomized comparison of metabolic and renal effects of saquinavir/r or atazanavir/r plus tenofovir/emtricitabine in treatment-naive HIV-1-infected patients. HIV Med 12(10):620–631PubMedCrossRefGoogle Scholar
  93. 93.
    Scherzer R et al (2011) Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection. AIDS 25(11):1405–1414PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Dolan SE et al (2006) Effects of a supervised home-based aerobic and progressive resistance training regimen in women infected with human immunodeficiency virus: a randomized trial. Arch Intern Med 166(11):1225–1231PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Falutz J et al (2008) Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS 22(14):1719–1728PubMedCrossRefGoogle Scholar
  96. 96.
    Falutz J et al (2007) Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med 357(23):2359–2370PubMedCrossRefGoogle Scholar
  97. 97.
    Falutz J et al (2010) Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab 95(9):4291–4304PubMedCrossRefGoogle Scholar
  98. 98.
    Brown TT, Glesby MJ (2011) Management of the metabolic effects of HIV and HIV drugs. Nat Rev Endocrinol 8(1):11–21PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Dobs AS et al (1988) Endocrine disorders in men infected with human immunodeficiency virus. Am J Med 84(3 Pt 2):611–616PubMedCrossRefGoogle Scholar
  100. 100.
    Arver S et al (1999) Serum dihydrotestosterone and testosterone concentrations in human immunodeficiency virus-infected men with and without weight loss. J Androl 20(5):611–618PubMedGoogle Scholar
  101. 101.
    Dacks JB, Peden AA, Field MC (2009) Evolution of specificity in the eukaryotic endomembrane system. Int J Biochem Cell Biol 41(2):330–340PubMedCrossRefGoogle Scholar
  102. 102.
    Wong N, Levy M, Stephenson I (2017) Hypogonadism in the HIV-Infected Man. Curr Treat Options Infect Dis 9(1):104–116PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Ashby J, Goldmeier D, Sadeghi-Nejad H (2014) Hypogonadism in human immunodeficiency virus-positive men. Korean J Urol 55(1):9–16PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Rochira V et al (2011) Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS ONE 6(12):e28512PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Rochira V, Guaraldi G (2014) Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am 43(3):709–730PubMedCrossRefGoogle Scholar
  106. 106.
    Khera M et al (2016) Adult-onset hypogonadism. Mayo Clin Proc 91(7):908–926PubMedCrossRefGoogle Scholar
  107. 107.
    Kirk JB, Goetz MB (2009) Human immunodeficiency virus in an aging population, a complication of success. J Am Geriatr Soc 57(11):2129–2138PubMedCrossRefGoogle Scholar
  108. 108.
    Aaltonen T et al (2012) Measurement of Bs0– > Ds(*) + Ds(*)- branching ratios. Phys Rev Lett 108(20):201801PubMedCrossRefGoogle Scholar
  109. 109.
    Selvin E et al (2007) Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care 30(2):234–238PubMedCrossRefGoogle Scholar
  110. 110.
    Cubero JM et al (2011) Prevalence of metabolic syndrome among human immunodeficiency virus-infected subjects is widely influenced by the diagnostic criteria. Metab Syndr Relat Disord 9(5):345–351PubMedCrossRefGoogle Scholar
  111. 111.
    Samaras K et al (2007) Prevalence of metabolic syndrome in HIV-infected patients receiving highly active antiretroviral therapy using International Diabetes Foundation and Adult Treatment Panel III criteria: associations with insulin resistance, disturbed body fat compartmentalization, elevated C-reactive protein, and (corrected) hypoadiponectinemia. Diabetes Care 30(1):113–119PubMedCrossRefGoogle Scholar
  112. 112.
    Klein RS et al (2005) Androgen levels in older men who have or who are at risk of acquiring HIV infection. Clin Infect Dis 41(12):1794–1803PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Roubenoff R et al (2002) Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men. Am J Physiol Endocrinol Metab 283(1):E138–E145PubMedCrossRefGoogle Scholar
  114. 114.
    Rochira V et al (2015) Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study. Andrology 3(2):298–308PubMedCrossRefGoogle Scholar
  115. 115.
    Collazos J (2007) Sexual dysfunction in the highly active antiretroviral therapy era. AIDS Rev 9(4):237–245PubMedGoogle Scholar
  116. 116.
    Bhasin S et al (2010) Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 95(6):2536–2559PubMedCrossRefGoogle Scholar
  117. 117.
    Clumeck N et al (2008) European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of HIV-infected adults. HIV Med 9(2):65–71PubMedCrossRefGoogle Scholar
  118. 118.
    Rosner W et al (2007) Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 92(2):405–413PubMedCrossRefGoogle Scholar
  119. 119.
    Ho CK et al (2006) Calculated free testosterone in men: comparison of four equations and with free androgen index. Ann Clin Biochem 43(Pt 5):389–397PubMedCrossRefGoogle Scholar
  120. 120.
    Mondul AM et al (2005) Age at natural menopause and cause-specific mortality. Am J Epidemiol 162(11):1089–1097PubMedCrossRefGoogle Scholar
  121. 121.
    Kanapathipillai R, Hickey M, Giles M (2013) Human immunodeficiency virus and menopause. Menopause 20(9):983–990PubMedCrossRefGoogle Scholar
  122. 122.
    Schoenbaum EE et al (2005) HIV infection, drug use, and onset of natural menopause. Clin Infect Dis 41(10):1517–1524PubMedCrossRefGoogle Scholar
  123. 123.
    Fantry LE et al (2005) Age of menopause and menopausal symptoms in HIV-infected women. AIDS Patient Care STDS 19(11):703–711PubMedCrossRefGoogle Scholar
  124. 124.
    Miller SA et al (2005) Menopause symptoms in HIV-infected and drug-using women. Menopause 12(3):348–356PubMedCrossRefGoogle Scholar
  125. 125.
    Brown TT, Qaqish RB (2006) Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS 20(17):2165–2174PubMedCrossRefGoogle Scholar
  126. 126.
    McComsey GA et al (2010) Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis 51(8):937–946PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Triant VA et al (2008) Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 93(9):3499–3504PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Young B et al (2011) Increased rates of bone fracture among HIV-infected persons in the HIV Outpatient Study (HOPS) compared with the US general population, 2000–2006. Clin Infect Dis 52(8):1061–1068PubMedCrossRefGoogle Scholar
  129. 129.
    Santi D et al (2016) Serum total estradiol, but not testosterone is associated with reduced bone mineral density (BMD) in HIV-infected men: a cross-sectional, observational study. Osteoporos Int 27(3):1103–1114PubMedCrossRefGoogle Scholar
  130. 130.
    Brown TT et al (2015) Recommendations for evaluation and management of bone disease in HIV. Clin Infect Dis 60(8):1242–1251PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Fakruddin JM, Laurence J (2003) HIV envelope gp120-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/RANKL cross-talk. J Biol Chem 278(48):48251–48258PubMedCrossRefGoogle Scholar
  132. 132.
    Gazzola L et al (2013) Association between peripheral T-lymphocyte activation and impaired bone mineral density in HIV-infected patients. J Transl Med 11:51PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Brown TT et al (2009) Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. J Acquir Immune Defic Syndr 51(5):554–561PubMedCrossRefGoogle Scholar
  134. 134.
    Paccou J et al (2009) Bone loss in patients with HIV infection. Joint Bone Spine 76(6):637–641PubMedCrossRefGoogle Scholar
  135. 135.
    Maalouf NM et al (2013) Hepatitis C co-infection and severity of liver disease as risk factors for osteoporotic fractures among HIV-infected patients. J Bone Miner Res 28(12):2577–2583PubMedCrossRefGoogle Scholar
  136. 136.
    El-Maouche D et al (2011) Controlled HIV viral replication, not liver disease severity associated with low bone mineral density in HIV/HCV co-infection. J Hepatol 55(4):770–776PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Eckard AR, McComsey GA (2014) Vitamin D deficiency and altered bone mineral metabolism in HIV-infected individuals. Curr HIV/AIDS Rep 11(3):263–270PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Lo Re V et al (2012) Risk of hip fracture associated with hepatitis C virus infection and hepatitis C/human immunodeficiency virus coinfection. Hepatology 56(5):1688–1698PubMedCrossRefGoogle Scholar
  139. 139.
    Gilsanz V et al (2009) Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab 94(9):3387–3393PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Clerici M, Shearer GM (1993) A TH1→TH2 switch is a critical step in the etiology of HIV infection. Immunol Today 14(3):107–111PubMedCrossRefGoogle Scholar
  141. 141.
    Chew N et al (2014) HIV-1 tat and rev upregulates osteoclast bone resorption. J Int AIDS Soc 17(4 Suppl 3):19724PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Panayiotopoulos A, Bhat N, Bhangoo A (2013) Bone and vitamin D metabolism in HIV. Rev Endocr Metab Disord 14(2):119–125PubMedCrossRefGoogle Scholar
  143. 143.
    Fakruddin JM, Laurence J (2004) Interactions among human immunodeficiency virus (HIV)-1, interferon-gamma and receptor of activated NF-kappa B ligand (RANKL): implications for HIV pathogenesis. Clin Exp Immunol 137(3):538–545PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Rosen CJ, Klibanski A (2009) Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. Am J Med 122(5):409–414PubMedCrossRefGoogle Scholar
  145. 145.
    Huang JS et al (2013) Bone mineral density effects of randomized regimen and nucleoside reverse transcriptase inhibitor selection from ACTG A5142. HIV Clin Trials 14(5):224–234PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Schafer JJ, Manlangit K, Squires KE (2013) Bone health and human immunodeficiency virus infection. Pharmacotherapy 33(6):665–682PubMedCrossRefGoogle Scholar
  147. 147.
    Mateo L et al (2016) Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients. Clin Rheumatol 35(5):1271–1279PubMedCrossRefGoogle Scholar
  148. 148.
    Sax PE et al (2015) Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet 385(9987):2606–2615PubMedCrossRefGoogle Scholar
  149. 149.
    Brown TT et al (2015) Changes in bone mineral density after initiation of antiretroviral treatment with tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. J Infect Dis 212(8):1241–1249PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Ofotokun I et al (2016) Antiretroviral therapy induces a rapid increase in bone resorption that is positively associated with the magnitude of immune reconstitution in HIV infection. AIDS 30(3):405–414PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Mazzotta E et al (2015) Prevalence and predictors of low bone mineral density and fragility fractures among HIV-infected patients at one Italian center after universal DXA screening: sensitivity and specificity of current guidelines on bone mineral density management. AIDS Patient Care STDS 29(4):169–180PubMedCrossRefGoogle Scholar
  152. 152.
    Brown TT (2013) Challenges in the management of osteoporosis and vitamin D deficiency in HIV infection. Top Antivir Med 21(3):115–118PubMedGoogle Scholar
  153. 153.
    Force, U.S.P.S.T. (2011) Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med 154(5):356–364CrossRefGoogle Scholar
  154. 154.
    Bloch M et al (2014) Switch from tenofovir to raltegravir increases low bone mineral density and decreases markers of bone turnover over 48 weeks. HIV Med 15(6):373–380PubMedCrossRefGoogle Scholar
  155. 155.
    Negredo E et al (2014) Improvement in bone mineral density after switching from tenofovir to abacavir in HIV-1-infected patients with low bone mineral density: two-centre randomized pilot study (OsteoTDF study). J Antimicrob Chemother 69(12):3368–3371PubMedCrossRefGoogle Scholar
  156. 156.
    Guaraldi G et al (2004) Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis. HIV Clin Trials 5(5):269–277PubMedCrossRefGoogle Scholar
  157. 157.
    Mondy K et al (2005) Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection. J Acquir Immune Defic Syndr 38(4):426–431PubMedCrossRefGoogle Scholar
  158. 158.
    McComsey GA et al (2007) Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS 21(18):2473–2482PubMedCrossRefGoogle Scholar
  159. 159.
    Negredo E et al (2015) Comparison of two different strategies of treatment with zoledronate in HIV-infected patients with low bone mineral density: single dose versus two doses in 2 years. HIV Med 16(7):441–448PubMedCrossRefGoogle Scholar
  160. 160.
    Bolland MJ et al (2012) Effects of intravenous zoledronate on bone turnover and bone density persist for at least five years in HIV-infected men. J Clin Endocrinol Metab 97(6):1922–1928PubMedCrossRefGoogle Scholar
  161. 161.
    Ofotokun I et al (2016) A single-dose zoledronic acid infusion prevents antiretroviral therapy-induced bone loss in treatment-naive HIV-infected patients: a phase IIb trial. Clin Infect Dis 63(5):663–671PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Pinzone MR et al (2014) Is there enough evidence to use bisphosphonates in HIV-infected patients? A systematic review and meta-analysis. AIDS Rev 16(4):213–222PubMedGoogle Scholar
  163. 163.
    Hoffmann CJ, Brown TT (2007) Thyroid function abnormalities in HIV-infected patients. Clin Infect Dis 45(4):488–494PubMedCrossRefGoogle Scholar
  164. 164.
    Ji S et al (2016) Prevalence and influencing factors of thyroid dysfunction in HIV-infected patients. Biomed Res Int 2016:3874257PubMedPubMedCentralGoogle Scholar
  165. 165.
    Grappin M et al (2000) Increased prevalence of subclinical hypothyroidism in HIV patients treated with highly active antiretroviral therapy. AIDS 14(8):1070–1072PubMedCrossRefGoogle Scholar
  166. 166.
    Collazos J, Ibarra S, Mayo J (2003) Thyroid hormones in HIV-infected patients in the highly active antiretroviral therapy era: evidence of an interrelation between the thyroid axis and the immune system. AIDS 17(5):763–765PubMedCrossRefGoogle Scholar
  167. 167.
    Garber JR et al (2012) Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 22(12):1200–1235PubMedCrossRefGoogle Scholar
  168. 168.
    French MA (2009) HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis 48(1):101–107PubMedCrossRefGoogle Scholar
  169. 169.
    Madeddu G et al (2006) Thyroid function in human immunodeficiency virus patients treated with highly active antiretroviral therapy (HAART): a longitudinal study. Clin Endocrinol (Oxf) 64(4):375–383Google Scholar
  170. 170.
    Jubault V et al (2000) Sequential occurrence of thyroid autoantibodies and Graves’ disease after immune restoration in severely immunocompromised human immunodeficiency virus-1-infected patients. J Clin Endocrinol Metab 85(11):4254–4257PubMedGoogle Scholar
  171. 171.
    Bahn RS et al (2011) Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract 17(3):456–520PubMedCrossRefGoogle Scholar
  172. 172.
    Welch K et al (1984) Autopsy findings in the acquired immune deficiency syndrome. JAMA 252(9):1152–1159PubMedCrossRefGoogle Scholar
  173. 173.
    Sawaya BE et al (2000) Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. J Biol Chem 275(45):35209–35214PubMedCrossRefGoogle Scholar
  174. 174.
    Kino T et al (1999) The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor. J Exp Med 189(1):51–62PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Norbiato G et al (1992) Cortisol resistance in acquired immunodeficiency syndrome. J Clin Endocrinol Metab 74(3):608–613PubMedGoogle Scholar
  176. 176.
    Raffi F et al (1991) Endocrine function in 98 HIV-infected patients: a prospective study. AIDS 5(6):729–733PubMedCrossRefGoogle Scholar
  177. 177.
    Biglino A et al (1995) Altered adrenocorticotropin and cortisol response to corticotropin-releasing hormone in HIV-1 infection. Eur J Endocrinol 133(2):173–179PubMedCrossRefGoogle Scholar
  178. 178.
    Verges B et al (1989) Adrenal function in HIV infected patients. Acta Endocrinol (Copenh) 121(5):633–637CrossRefGoogle Scholar
  179. 179.
    Glasgow BJ et al (1985) Adrenal pathology in the acquired immune deficiency syndrome. Am J Clin Pathol 84(5):594–597PubMedCrossRefGoogle Scholar
  180. 180.
    Baker R, Rook GA, Zumla A (1997) Adrenal function and the hypothalamo-pituitary adrenal axis in immunodeficiency virus-associated tuberculosis. Int J Tuberc Lung Dis 1(3):289–290PubMedCrossRefGoogle Scholar
  181. 181.
    Arabi Y et al (1996) Adrenal insufficiency, recurrent bacteremia, and disseminated abscesses caused by Nocardia asteroides in a patient with acquired immunodeficiency syndrome. Diagn Microbiol Infect Dis 24(1):47–51PubMedCrossRefGoogle Scholar
  182. 182.
    Schwartz LJ et al (1991) Endocrine function in children with human immunodeficiency virus infection. Am J Dis Child 145(3):330–333PubMedGoogle Scholar
  183. 183.
    Radin DR et al (1993) AIDS-related non-Hodgkin’s lymphoma: abdominal CT findings in 112 patients. AJR Am J Roentgenol 160(5):1133–1139PubMedCrossRefGoogle Scholar
  184. 184.
    Tappero JW et al (1993) Kaposi’s sarcoma. Epidemiology, pathogenesis, histology, clinical spectrum, staging criteria and therapy. J Am Acad Dermatol 28(3):371–395PubMedCrossRefGoogle Scholar
  185. 185.
    Eledrisi MS, Verghese AC (2001) Adrenal insufficiency in HIV infection: a review and recommendations. Am J Med Sci 321(2):137–144PubMedCrossRefGoogle Scholar
  186. 186.
    Mann M et al (1997) Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature. Arch Intern Med 157(15):1651–1656PubMedCrossRefGoogle Scholar
  187. 187.
    Subramanian S et al (1997) Clinical adrenal insufficiency in patients receiving megestrol therapy. Arch Intern Med 157(9):1008–1011PubMedCrossRefGoogle Scholar
  188. 188.
    Putignano P et al (1998) The effects of anti-convulsant drugs on adrenal function. Horm Metab Res 30(6–7):389–397PubMedCrossRefGoogle Scholar
  189. 189.
    Foisy MM et al (2008) Adrenal suppression and Cushing’s syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIV Med 9(6):389–396PubMedCrossRefGoogle Scholar
  190. 190.
    Prasanthai V et al (2007) Prevalence of adrenal insufficiency in critically ill patients with AIDS. J Med Assoc Thai 90(9):1768–1774PubMedGoogle Scholar
  191. 191.
    Chrousos GP, Zapanti ED (2014) Hypothalamic-pituitary-adrenal axis in HIV infection and disease. Endocrinol Metab Clin North Am 43(3):791–806PubMedCrossRefGoogle Scholar
  192. 192.
    Kyriazopoulou V, Parparousi O, Vagenakis AG (1984) Rifampicin-induced adrenal crisis in addisonian patients receiving corticosteroid replacement therapy. J Clin Endocrinol Metab 59(6):1204–1206PubMedCrossRefGoogle Scholar
  193. 193.
    Rochira V, Guaraldi G (2017) Growth hormone deficiency and human immunodeficiency virus. Best Pract Res Clin Endocrinol Metab 31(1):91–111PubMedCrossRefGoogle Scholar
  194. 194.
    Falutz J et al (2005) A placebo-controlled, dose-ranging study of a growth hormone releasing factor in HIV-infected patients with abdominal fat accumulation. AIDS 19(12):1279–1287PubMedCrossRefGoogle Scholar
  195. 195.
    Stanley TL et al (2014) Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA 312(4):380–389PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Ram S et al (2004) Serum prolactin in human immunodeficiency virus infection. Clin Lab 50(9–10):617–620PubMedGoogle Scholar
  197. 197.
    Hutchinson J et al (2000) Galactorrhoea and hyperprolactinaemia associated with protease-inhibitors. Lancet 356(9234):1003–1004PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2018

Authors and Affiliations

  1. 1.Division of Endocrinology and Metabolism, Department of MedicineUConn HealthFarmingtonUSA
  2. 2.Division of Infectious DiseasesUConn HealthFarmingtonUSA
  3. 3.Department of MedicineUConn HealthFarmingtonUSA

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