Reviews in Endocrine and Metabolic Disorders

, Volume 14, Issue 2, pp 133–140

Insulin resistance, lipodystrophy and cardiometabolic syndrome in HIV/AIDS

Article

Abstract

HIV associated insulin resistance, lipodistrophy and cardiometabolic syndrome have been extensively studied and continue to be the scope of much research. There is compelling evidence that both the HIV itself and the therapeutical regimes are major contributors to all of these associated comorbidities. HIV has increasingly been recognized as a disease of accelerated aging, manifested by increased progression of vascular disease and cellular markers of aging. The antiretroviral medication can increase insulin resistance and cause lipotoxocity and HIV-associated lipodystrophy leading to cardiovascular pathology. In this article we review the pathogenesis, management, and prevention of the long-term complications of HIV and its therapies, including cardiovascular disease, lipodystrophy, and insulin resistance along with the growing focus on biomarkers to predict development of end-organ disease. Through a focused literature search we review the established evidence, the developing research about the treatment strategies in treated HIV infection as well as identify potential areas for future research.

Keywords

HIV Lipodistrophy Insulin resistance Metabolic syndrome Cardiometabolic syndrome Antiretroviral therapy HAART 

References

  1. 1.
    Gutierrez AD, Balasubramanyam A. Dysregulation of glucose metabolism in HIV patients: epidemiology, mechanisms, and management. Endocrine. 2012;41:1–10.CrossRefPubMedGoogle Scholar
  2. 2.
    Hadigan C, Meigs JB, Corcoran C, Rietschel P, Piecuch S, Basgoz N, et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis Off Publ Infect Dis Soc Am. 2001;32:130–9.CrossRefGoogle Scholar
  3. 3.
    Magkos F, Mantzoros CS. Body fat redistribution and metabolic abnormalities in HIV-infected patients on highly active antiretroviral therapy: novel insights into pathophysiology and emerging opportunities for treatment. Metabolism. 2011;60:749–53.CrossRefPubMedGoogle Scholar
  4. 4.
    Brar I, Shuter J, Thomas A, Daniels E, Absalon J. A comparison of factors associated with prevalent diabetes mellitus among HIV-Infected antiretroviral-naive individuals versus individuals in the National Health and Nutritional Examination Survey cohort. J Acquir Immune Defic Syndr. 2007;45:66–71.CrossRefPubMedGoogle Scholar
  5. 5.
    Butt AA, McGinnis K, Rodriguez-Barradas MC, Crystal S, Simberkoff M, Goetz MB, et al. HIV infection and the risk of diabetes mellitus. AIDS. 2009;23:1227–34.CrossRefPubMedGoogle Scholar
  6. 6.
    Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005;165:1179–84.CrossRefPubMedGoogle Scholar
  7. 7.
    De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, et al. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Diabetes Care. 2008;31:1224–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem. 2000;275:20251–4.CrossRefPubMedGoogle Scholar
  9. 9.
    Shikuma CM, Day LJ, Gerschenson M. Insulin resistance in the HIV-infected population: the potential role of mitochondrial dysfunction. Curr Drug Targets Infect Disord. 2005;5:255–62.CrossRefPubMedGoogle Scholar
  10. 10.
    Mehta SH, Moore RD, Thomas DL, Chaisson RE, Sulkowski MS. The effect of HAART and HCV infection on the development of hyperglycemia among HIV-infected persons. J Acquir Immune Defic Syndr. 2003;33:577–84.CrossRefPubMedGoogle Scholar
  11. 11.
    Hruz PW. Molecular mechanisms for insulin resistance in treated HIV-infection. Best Pract Res Clin Endocrinol Metab. 2011;25:459–68.CrossRefPubMedGoogle Scholar
  12. 12.
    Fleischman A, Johnsen S, Systrom DM, Hrovat M, Farrar CT, Frontera W, et al. Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults. Am J Physiol Endocrinol Metab. 2007;292:E1666–73.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    Paik IJ, Kotler DP. The prevalence and pathogenesis of diabetes mellitus in treated HIV-infection. Best Pract Res Clin Endocrinol Metab. 2011;25:469–78.CrossRefPubMedGoogle Scholar
  15. 15.
    Troll JG. Approach to dyslipidemia, lipodystrophy, and cardiovascular risk in patients with HIV infection. Curr Atheroscler Rep. 2011;13:51–6.Google Scholar
  16. 16.
    European Paediatric Lipodystrophy Group. Antiretroviral therapy, fat redistribution and hyperlipidaemia in HIV-infected children in Europe. AIDS. 2004;18:1443–51.Google Scholar
  17. 17.
    Bockhorst JL, Ksseiry I, Toye M, Chipkin SR, Stechenberg BW, Fisher DJ, et al. Evidence of human immunodeficiency virus-associated lipodystrophy syndrome in children treated with protease inhibitors. Pediatr Infect Dis J. 2003;22:463–5.PubMedGoogle Scholar
  18. 18.
    Alam N, Cortina-Borja M, Goetghebuer T, Marczynska M, Vigano A, Thorne C. Body fat abnormality in HIV-infected children and adolescents living in Europe: prevalence and risk factors. J Acquir Immune Defic Syndr. 2012;59:314–24.CrossRefPubMedGoogle Scholar
  19. 19.
    Grunfeld C, Saag M, Cofrancesco Jr J, Lewis CE, Kronmal R, Heymsfield S, et al. Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy. AIDS. 2010;24:1717–26.CrossRefPubMedGoogle Scholar
  20. 20.
    Seybold U. Metabolic syndrome and cardiovascular diseases in HIV patients. MMW Fortschr Med. 2012;154 Suppl 1:30–1.CrossRefPubMedGoogle Scholar
  21. 21.
    Samaras K, Wand H, Law M, Emery S, Cooper D, Carr A. 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. 2007;30:113–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Seminari E, Tinelli C, Minoli L, Sacchi P, Filice G, Zocchetti C, et al. Evaluation of the risk factors associated with lipodystrophy development in a cohort of HIV-positive patients. Antivir Ther. 2002;7:175–80.PubMedGoogle Scholar
  23. 23.
    Hadigan C, Liebau J, Andersen R, Holalkere NS, Sahani DV. Magnetic resonance spectroscopy of hepatic lipid content and associated risk factors in HIV infection. J Acquir Immune Defic Syndr. 2007;46:312–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Torriani M, Hadigan C, Jensen ME, Grinspoon S. Psoas muscle attenuation measurement with computed tomography indicates intramuscular fat accumulation in patients with the HIV-lipodystrophy syndrome. J Appl Physiol. 2003;95:1005–10.PubMedGoogle Scholar
  25. 25.
    Safrin S, Grunfeld C. Fat distribution and metabolic changes in patients with HIV infection. AIDS. 1999;13:2493–505.CrossRefPubMedGoogle Scholar
  26. 26.
    Shlay JC, Sharma S, Peng G, Gibert CL, Grunfeld C. The effect of individual antiretroviral drugs on body composition in HIV-infected persons initiating highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2009;51:298–304.CrossRefPubMedGoogle Scholar
  27. 27.
    Seigneur M, Constans J, Blann A, Renard M, Pellegrin JL, Amiral J, et al. Soluble adhesion molecules and endothelial cell damage in HIV infected patients. Thromb Haemost. 1997;77:646–9.PubMedGoogle Scholar
  28. 28.
    Shen YM, Frenkel EP. Thrombosis and a hypercoagulable state in HIV-infected patients. Clin Appl Thromb Hemost. 2004;10:277–80.CrossRefPubMedGoogle Scholar
  29. 29.
    Karmochkine M, Ankri A, Calvez V, Bonmarchant M, Coutellier A, Herson S. Plasma hypercoagulability is correlated to plasma HIV load. Thromb Haemost. 1998;80:208–9.PubMedGoogle Scholar
  30. 30.
    Grunfeld C, Delaney JA, Wanke C, Currier JS, Scherzer R, Biggs ML, et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS. 2009;23:1841–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Kaplan RC, Kingsley LA, Gange SJ, Benning L, Jacobson LP, Lazar J, et al. Low CD4+ T-cell count as a major atherosclerosis risk factor in HIV-infected women and men. AIDS. 2008;22:1615–24.CrossRefPubMedGoogle Scholar
  32. 32.
    Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. J Acquir Immune Defic Syndr. 2009;51:268–73.CrossRefPubMedGoogle Scholar
  33. 33.
    Samaras K, Gan SK, Peake PW, Carr A, Campbell LV. Proinflammatory markers, insulin sensitivity, and cardiometabolic risk factors in treated HIV infection. Obesity (Silver Spring). 2009;17:53–9.CrossRefGoogle Scholar
  34. 34.
    Sankale JL, Tong Q, Hadigan CM, Tan G, Grinspoon SK, Kanki PJ, et al. Regulation of adiponectin in adipocytes upon exposure to HIV-1. HIV Med. 2006;7:268–74.CrossRefPubMedGoogle Scholar
  35. 35.
    Jones SP, Qazi N, Morelese J, Lebrecht D, Sutinen J, Yki-Jarvinen H, et al. Assessment of adipokine expression and mitochondrial toxicity in HIV patients with lipoatrophy on stavudine- and zidovudine-containing regimens. J Acquir Immune Defic Syndr. 2005;40:565–72.CrossRefPubMedGoogle Scholar
  36. 36.
    Resino S, Micheloud D, Lorente R, Bellon JM, Navarro ML, Munoz-Fernandez MA. Adipokine profiles and lipodystrophy in HIV-infected children during the first 4 years on highly active antiretroviral therapy. HIV Med. 2011;12:54–60.CrossRefPubMedGoogle Scholar
  37. 37.
    Bogner JR, Vielhauer V, Beckmann RA, Michl G, Wille L, Salzberger B, et al. Stavudine versus zidovudine and the development of lipodystrophy. J Acquir Immune Defic Syndr. 2001;27:237–44.PubMedGoogle Scholar
  38. 38.
    Lichtenstein KA, Delaney KM, Armon C, Ward DJ, Moorman AC, Wood KC, et al. Incidence of and risk factors for lipoatrophy (abnormal fat loss) in ambulatory HIV-1-infected patients. J Acquir Immune Defic Syndr. 2003;32:48–56.CrossRefPubMedGoogle Scholar
  39. 39.
    George JA, Venter WD, Van Deventer HE, Crowther NJ. A longitudinal study of the changes in body fat and metabolic parameters in a South African population of HIV-positive patients receiving an antiretroviral therapeutic regimen containing stavudine. AIDS Res Hum Retrovir. 2009;25:771–81.CrossRefPubMedGoogle Scholar
  40. 40.
    Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet. 1999;353:2093–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Chene G, Angelini E, Cotte L, Lang JM, Morlat P, Rancinan C, et al. Role of long-term nucleoside-analogue therapy in lipodystrophy and metabolic disorders in human immunodeficiency virus-infected patients. Clin Infect Dis Off Publ Infect Dis Soc Am. 2002;34:649–57.CrossRefGoogle Scholar
  42. 42.
    Ene L, Goetghebuer T, Hainaut M, Peltier A, Toppet V, Levy J. Prevalence of lipodystrophy in HIV-infected children: a cross-sectional study. Eur J Pediatr. 2007;166:13–21.CrossRefPubMedGoogle Scholar
  43. 43.
    Beregszaszi M, Dollfus C, Levine M, Faye A, Deghmoun S, Bellal N, et al. Longitudinal evaluation and risk factors of lipodystrophy and associated metabolic changes in HIV-infected children. J Acquir Immune Defic Syndr. 2005;40:161–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Desai N, Mullen P, Mathur M. Lipodystrophy in pediatric HIV. Indian J Pediatr. 2008;75:351–4.CrossRefPubMedGoogle Scholar
  45. 45.
    Bastard JP, Caron M, Vidal H, Jan V, Auclair M, Vigouroux C, et al. Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance. Lancet. 2002;359:1026–31.CrossRefPubMedGoogle Scholar
  46. 46.
    Martinez E, Gatell J. Metabolic abnormalities and use of HIV-1 protease inhibitors. Lancet. 1998;352:821–2.CrossRefPubMedGoogle Scholar
  47. 47.
    Gupta S, Knight AG, Losso BY, Ingram DK, Keller JN, Bruce-Keller AJ. Brain injury caused by HIV protease inhibitors: role of lipodystrophy and insulin resistance. Antivir Res. 2012;95:19–29.CrossRefPubMedGoogle Scholar
  48. 48.
    Rusconi S, Giacomet V, Mameli C, Vigano A, Vigano O, Adorni F, et al. Efficacy and safety of a dual boosted protease inhibitor-based regimen, atazanavir and fosamprenavir/ritonavir, against HIV: experience in a pediatric population. BMC Infect Dis. 2012;12:179.CrossRefPubMedGoogle Scholar
  49. 49.
    Joly V, Flandre P, Meiffredy V, Leturque N, Harel M, Aboulker JP, et al. Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial. AIDS. 2002;16:2447–54.CrossRefPubMedGoogle Scholar
  50. 50.
    Shlay JC, Bartsch G, Peng G, Wang J, Grunfeld C, Gibert CL, et al. Long-term body composition and metabolic changes in antiretroviral naive persons randomized to protease inhibitor-, nonnucleoside reverse transcriptase inhibitor-, or protease inhibitor plus nonnucleoside reverse transcriptase inhibitor-based strategy. J Acquir Immune Defic Syndr. 2007;44:506–17.CrossRefPubMedGoogle Scholar
  51. 51.
    McComsey GA, Kitch D, Sax PE, Tebas P, Tierney C, Jahed NC, et al. Peripheral and central fat changes in subjects randomized to abacavir-lamivudine or tenofovir-emtricitabine with atazanavir-ritonavir or efavirenz: ACTG Study A5224s. Clin Infect Dis Off Publ Infect Dis Soc Am. 2011;53:185–96.CrossRefGoogle Scholar
  52. 52.
    Mondy K, Overton ET, Grubb J, Tong S, Seyfried W, Powderly W, et al. Metabolic syndrome in HIV-infected patients from an urban, midwestern US outpatient population. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;44:726–34.CrossRefGoogle Scholar
  53. 53.
    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.CrossRefPubMedGoogle Scholar
  54. 54.
    Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5:e203.CrossRefPubMedGoogle Scholar
  55. 55.
    Solages A, Vita JA, Thornton DJ, Murray J, Heeren T, Craven DE, et al. Endothelial function in HIV-infected persons. Clin Infect Dis Off Publ Infect Dis Soc Am. 2006;42:1325–32.CrossRefGoogle Scholar
  56. 56.
    Baliga RS, Chaves AA, Jing L, Ayers LW, Bauer JA. AIDS-related vasculopathy: evidence for oxidative and inflammatory pathways in murine and human AIDS. Am J Physiol Heart Circ Physiol. 2005;289:H1373–80.CrossRefPubMedGoogle Scholar
  57. 57.
    Esser S, Gelbrich G, Brockmeyer N, Goehler A, Schadendorf D, Erbel R, et al. Prevalence of cardiovascular diseases in HIV-infected outpatients: results from a prospective, multicenter cohort study. Clin Res Cardiol. 2013;102:203–13.Google Scholar
  58. 58.
    Mavroudis CA, Majumder B, Loizides S, Christophides T, Johnson M, Rakhit RD. Coronary artery disease and HIV; getting to the HAART of the matter. Int J Cardiol. 2012;S0167-5273:01149–7.Google Scholar
  59. 59.
    Francisci D, Giannini S, Baldelli F, Leone M, Belfiori B, Guglielmini G, et al. HIV type 1 infection, and not short-term HAART, induces endothelial dysfunction. AIDS. 2009;23:589–96.CrossRefPubMedGoogle Scholar
  60. 60.
    Byrnes M, Travers K, Burns M, Sapra S. A systematic literature review examining soluble and cellular biomarkers in HIV patients receiving antiretroviral therapy. J Int AIDS Soc. 2012;15:18172.Google Scholar
  61. 61.
    Poudel-Tandukar K, Poudel KC, Jimba M, Kobayashi J, Johnson CA, Palmer PH. Serum 25-hydroxyvitamin D levels and C-reactive protein in persons with human immunodeficiency virus infection. AIDS Res Hum Retrovir. 2013;29:528–34.Google Scholar
  62. 62.
    Danesh J, Kaptoge S, Mann AG, Sarwar N, Wood A, Angleman SB, 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.CrossRefPubMedGoogle Scholar
  63. 63.
    Baker JV, Duprez D, Rapkin J, Hullsiek KH, Quick H, Grimm R, et al. Untreated HIV infection and large and small artery elasticity. J Acquir Immune Defic Syndr. 2009;52:25–31.CrossRefPubMedGoogle Scholar
  64. 64.
    Lafeuillade A, Alessi MC, Poizot-Martin I, Boyer-Neumann C, Zandotti C, Quilichini R, et al. Endothelial cell dysfunction in HIV infection. J Acquir Immune Defic Syndr. 1992;5:127–31.PubMedGoogle Scholar
  65. 65.
    Phillips AN, Carr A, Neuhaus J, Visnegarwala F, Prineas R, Burman WJ, et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther. 2008;13:177–87.PubMedGoogle Scholar
  66. 66.
    El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283–96.CrossRefPubMedGoogle Scholar
  67. 67.
    Ferraro S, Paolillo S, Gargiulo M, Costanzo P, Maggi P, Chirianni A, et al. Effect of antiretroviral therapy on carotid intima-media thickness in HIV-infected patients. G Ital Cardiol (Rome). 2009;10:596–601.Google Scholar
  68. 68.
    Guaraldi G, Stentarelli C, Zona S, Orlando G, Carli F, Ligabue G, et al. Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical atherosclerosis in human immunodeficiency virus infected subjects. Atherosclerosis. 2010;208:222–7.CrossRefPubMedGoogle Scholar
  69. 69.
    Guaraldi G, Zona S, Orlando G, Carli F, Ligabue G, Fiocchi F, et al. Progression of coronary artery calcium in men affected by human immunodeficiency virus infection. Int J Cardiovasc Imaging. 2012;28:935–41.CrossRefPubMedGoogle Scholar
  70. 70.
    Hsue PY, Hunt PW, Sinclair E, Bredt B, Franklin A, Killian M, et al. Increased carotid intima-media thickness in HIV patients is associated with increased cytomegalovirus-specific T-cell responses. AIDS. 2006;20:2275–83.CrossRefPubMedGoogle Scholar
  71. 71.
    Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356:1723–35.CrossRefPubMedGoogle Scholar
  72. 72.
    Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, 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.CrossRefPubMedGoogle Scholar
  73. 73.
    Mary-Krause M, Cotte L, Simon A, Partisani M, Costagliola D. Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS. 2003;17:2479–86.CrossRefPubMedGoogle Scholar
  74. 74.
    Friis-Moller N, Weber R, Reiss P, Thiebaut R, Kirk O, d’Arminio Monforte A, et al. Cardiovascular disease risk factors in HIV patients—association with antiretroviral therapy. Results from the DAD study. AIDS. 2003;17:1179–93.CrossRefPubMedGoogle Scholar
  75. 75.
    Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, 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.CrossRefPubMedGoogle Scholar
  76. 76.
    Emery S, Neuhaus JA, Phillips AN, Babiker A, Cohen CJ, Gatell JM, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008;197:1133–44.CrossRefPubMedGoogle Scholar
  77. 77.
    Ding X, Andraca-Carrera E, Cooper C, Miele P, Kornegay C, Soukup M, 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.CrossRefPubMedGoogle Scholar
  78. 78.
    Palella Jr FJ, Phair JP. Cardiovascular disease in HIV infection. Curr Opin HIV AIDS. 2011;6:266–71.CrossRefPubMedGoogle Scholar
  79. 79.
    Fitch KV, Anderson EJ, Hubbard JL, Carpenter SJ, Waddell WR, Caliendo AM, et al. Effects of a lifestyle modification program in HIV-infected patients with the metabolic syndrome. AIDS. 2006;20:1843–50.CrossRefPubMedGoogle Scholar
  80. 80.
    Fitch K, Abbara S, Lee H, Stavrou E, Sacks R, Michel T, et al. Effects of lifestyle modification and metformin on atherosclerotic indices among HIV-infected patients with the metabolic syndrome. AIDS. 2012;26:587–97.CrossRefPubMedGoogle Scholar
  81. 81.
    Botros D, Somarriba G, Neri D, Miller TL. Interventions to address chronic disease and HIV: strategies to promote exercise and nutrition among HIV-infected individuals. Curr HIV/AIDS Rep. 2012;9:351–63.CrossRefPubMedGoogle Scholar
  82. 82.
    Robinson FP, Quinn LT, Rimmer JH. Effects of high-intensity endurance and resistance exercise on HIV metabolic abnormalities: a pilot study. Biol Res Nurs. 2007;8:177–85.CrossRefPubMedGoogle Scholar
  83. 83.
    Lindegaard B, Hansen T, Hvid T, van Hall G, Plomgaard P, Ditlevsen S, et al. The effect of strength and endurance training on insulin sensitivity and fat distribution in human immunodeficiency virus-infected patients with lipodystrophy. J Clin Endocrinol Metab. 2008;93:3860–9.CrossRefPubMedGoogle Scholar
  84. 84.
    Gianotti N, Visco F, Galli L, Barda B, Piatti P, Salpietro S, et al. Detecting impaired glucose tolerance or type 2 diabetes mellitus by means of an oral glucose tolerance test in HIV-infected patients. HIV Med. 2011;12:109–17.CrossRefPubMedGoogle Scholar
  85. 85.
    Balasubramanyam A, Coraza I, Smith EO, Scott LW, Patel P, Iyer D, et al. Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of “heart positive,” a randomized, controlled trial. J Clin Endocrinol Metab. 2011;96:2236–47.CrossRefPubMedGoogle Scholar
  86. 86.
    PENTA Steering Committee. Paediatric European Network for Treatment of AIDS response to 2010 revision of World Health Organization recommendations on ‘Antiretroviral therapy for HIV infection in infants and children’. HIV Med. 2011;12:385–6.Google Scholar
  87. 87.
    Committee PS. Paediatric European Network for Treatment of AIDS (PENTA) treatment guidelines. In. 2009.Google Scholar
  88. 88.
    Moyle GJ, Sabin CA, Cartledge J, Johnson M, Wilkins E, Churchill D, et al. A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. AIDS. 2006;20:2043–50.CrossRefPubMedGoogle Scholar
  89. 89.
    Martin A, Smith DE, Carr A, Ringland C, Amin J, Emery S, et al. Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study. AIDS. 2004;18:1029–36.CrossRefPubMedGoogle Scholar
  90. 90.
    McComsey GA, Ward DJ, Hessenthaler SM, Sension MG, Shalit P, Lonergan JT, et al. Improvement in lipoatrophy associated with highly active antiretroviral therapy in human immunodeficiency virus-infected patients switched from stavudine to abacavir or zidovudine: the results of the TARHEEL study. Clin Infect Dis Off Publ Infect Dis Soc Am. 2004;38:263–70.CrossRefGoogle Scholar
  91. 91.
    Martinez E, Gonzalez-Cordon A, Podzamczer D, Domingo P, Negredo E, Gutierrez F, et al. Metabolic effects of atazanavir/ritonavir vs darunavir/ritonavir in combination with tenofovir/emtricitabine in antiretroviral-naive patients (ATADAR Study). J Int AIDS Soc. 2012;15:18202.Google Scholar
  92. 92.
    Overton ET, Arathoon E, Baraldi E, Tomaka F. Effect of darunavir on lipid profile in HIV-infected patients. HIV Clin Trials. 2012;13:256–70.CrossRefPubMedGoogle Scholar
  93. 93.
    Gotti D, Cesana BM, Albini L, Calabresi A, Izzo I, Foca E, et al. Increase in standard cholesterol and large HDL particle subclasses in antiretroviral-naive patients prescribed efavirenz compared to atazanavir/ritonavir. HIV Clin Trials. 2012;13:245–55.CrossRefPubMedGoogle Scholar
  94. 94.
    Aberg JA, Tebas P, Overton ET, Gupta SK, Sax PE, Landay A, et al. Metabolic effects of darunavir/ritonavir versus atazanavir/ritonavir in treatment-naive, HIV type 1-infected subjects over 48 weeks. AIDS Res Hum Retrovir. 2012;28:1184–95.CrossRefPubMedGoogle Scholar
  95. 95.
    Perez-Matute P, Perez-Martinez L, Rus A, Jareno M, Blanco J, Oteo J. Maraviroc shows differential effects on glucose uptake and lipolysis in human subcutaneous cultured adipocytes in comparison with omental adipocytes. J Int AIDS Soc. 2012;15:18306.Google Scholar
  96. 96.
    Wohl DA, Waters D, Simpson Jr RJ, Richard S, Schnell A, Napravnik S, et al. Ezetimibe alone reduces low-density lipoprotein cholesterol in HIV-infected patients receiving combination antiretroviral therapy. Clin Infect Dis Off Publ Infect Dis Soc Am. 2008;47:1105–8.CrossRefGoogle Scholar
  97. 97.
    Joven J, Menendez J, Fernandez-Sender L, Espinel E, Rull A, Beltran-Debon R, et al. Metformin: a cheap and well-tolerated drug that provides benefits for viral infections. HIV Med. 2013;14:233–40.Google Scholar
  98. 98.
    Mahmood K, Naeem M, Rahimnajjad NA. Metformin: the hidden chronicles of a magic drug. Eur J Intern Med. 2013;24:20–6.Google Scholar
  99. 99.
    Sheth SH, Larson RJ. The efficacy and safety of insulin-sensitizing drugs in HIV-associated lipodystrophy syndrome: a meta-analysis of randomized trials. BMC Infect Dis. 2010;10:183.CrossRefPubMedGoogle Scholar
  100. 100.
    Matthews LT, Giddy J, Ghebremichael M, Hampton J, Guarino AJ, Ewusi A, et al. A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy. PLoS One. 2011;6:e18736.CrossRefPubMedGoogle Scholar
  101. 101.
    Hansen BR, Haugaard SB, Jensen FK, Jensen JE, Andresen L, Iversen J, et al. Long-term high-physiological-dose growth hormone reduces intra-abdominal fat in HIV-infected patients with a neutral effect on glucose metabolism. HIV Med. 2010;11:266–75.CrossRefPubMedGoogle Scholar
  102. 102.
    Spooner LM, Olin JL. Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. Ann Pharmacother. 2012;46:240–7.CrossRefPubMedGoogle Scholar
  103. 103.
    Bedimo R. Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy. HIV AIDS (Auckl). 2011;3:69–79.Google Scholar
  104. 104.
    Cook DM, Rose SR. A review of guidelines for use of growth hormone in pediatric and transition patients. Pituitary. 2012;15:301–10.CrossRefPubMedGoogle Scholar
  105. 105.
    Macallan DC, Baldwin C, Mandalia S, Pandol-Kaljevic V, Higgins N, Grundy A, et al. Treatment of altered body composition in HIV-associated lipodystrophy: comparison of rosiglitazone, pravastatin, and recombinant human growth hormone. HIV Clin Trials. 2008;9:254–68.CrossRefPubMedGoogle Scholar
  106. 106.
    Falutz J, Potvin D, Mamputu JC, Assaad H, Zoltowska M, Michaud SE, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. J Acquir Immune Defic Syndr. 2010;53:311–22.CrossRefPubMedGoogle Scholar
  107. 107.
    Stanley TL, Falutz J, Marsolais C, Morin J, Soulban G, Mamputu JC, et al. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;54:1642–51.CrossRefGoogle Scholar
  108. 108.
    Magkos F, Brennan A, Sweeney L, Kang ES, Doweiko J, Karchmer AW, et al. Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study. Metabolism. 2011;60:1045–9.CrossRefPubMedGoogle Scholar
  109. 109.
    Luetkemeyer AF, Havlir DV, Currier JS. Complications of HIV disease and antiretroviral therapy. Top Antivir Med. 2012;20:48–60.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of PediatricsChildren’s Hospital at SUNY Downstate and Kings County Hospital CenterBrooklynUSA
  2. 2.Pediatric Endocrinology Divisions of Infants and Children’s Hospital of Brooklyn at MaimonidesChildren’s Hospital at SUNY Downstate and Kings County Hospital CenterBrooklynUSA

Personalised recommendations