Current HIV/AIDS Reports

, Volume 11, Issue 3, pp 271–278 | Cite as

Metabolic Syndrome, Diabetes, and Cardiovascular Risk in HIV

  • Linda M. Nix
  • Phyllis C. TienEmail author
Co-infections and Comorbidity (CM Wyatt and K Sigel, Section Editors)


HIV infection and its treatment have been associated with adipose tissue changes and disorders of glucose and lipid metabolism. The proportion of HIV-infected adults over the age of 50 is also growing placing HIV-infected adults at particular risk for metabolic perturbations and cardiovascular disease. The metabolic syndrome in HIV-infected adults has been increasingly studied but whether HIV is associated with greater risk remains unclear, likely because of the interplay of host, viral and antiretroviral factors that are associated with the components of the metabolic syndrome. The relationship between HIV and diabetes mellitus (DM) risk has also been debated. While the Framingham Risk Score is a well-accepted measure of 10-year cardiovascular risk in the general population, it may not accurately predict risk in the HIV setting due to HIV-related factors such as inflammation that are not accounted for. We summarize the recent literature on metabolic syndrome, DM, and cardiovascular risk in HIV-infected adults.


HIV Metabolic syndrome Diabetes Cardiovascular risk Framingham risk score Lipodystrophy syndrome 


Compliance with Ethics Guidelines

Conflict of Interest

Linda M. Nix declares that she has no conflict of interest.

Phyllis C. Tien reports grants from NIH, personal fees from BMS, personal fees from Genentech, and personal fees from Gilead outside the submitted work.

Human and Animal Rights and Informed Consent

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


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

  1. 1.
    Currier JS, Taylor A, Boyd F, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defici Syndr (1999). 2003;33(4):506–12.CrossRefGoogle Scholar
  2. 2.
    Grunfeld C, Delaney JA, Wanke C, et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS (London, England). 2009;23(14):1841–9.CrossRefGoogle Scholar
  3. 3.
    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(7):2506–12.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Sobieszczyk ME, Hoover DR, Anastos K, et al. Prevalence and predictors of metabolic syndrome among HIV-infected and HIV-uninfected women in the Women's Interagency HIV Study. J Acquir Immune Defici Syndr (1999). 2008;48(3):272–80.CrossRefGoogle Scholar
  5. 5.
    Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005;352(1):48–62.PubMedCrossRefGoogle Scholar
  6. 6.
    Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med. 2011;62:141–55.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5(10):e203.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Smith G. Statement of Senator Gordon H. Smith. Aging Hearing. HIV over fifty: exploring the new threat. Washington, DC: Senate Committee on Aging; 2005.Google Scholar
  9. 9.
    Reaven GM. Banting lecture 1988. Role Insulin Resist Hum Dis Diabetes. 1988;37(12):1595–607.Google Scholar
  10. 10.
    Ford ES. The metabolic syndrome and mortality from cardiovascular disease and all-causes: findings from the National Health and Nutrition Examination Survey II Mortality Study. Atherosclerosis. 2004;173(2):309–14.PubMedCrossRefGoogle Scholar
  11. 11.
    Alberti KG, Zimmet P, Shaw J. The metabolic syndrome–a new worldwide definition. Lancet. 2005;366(9491):1059–62.PubMedCrossRefGoogle Scholar
  12. 12.
    Grundy SM, Hansen B, Smith Jr SC, et al. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation. 2004;109(4):551–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS (London, England). 1998;12(7):F51–8.CrossRefGoogle Scholar
  14. 14.
    Bacchetti P, Gripshover B, Grunfeld C, et al. Fat distribution in men with HIV infection. J Acquir Immune Defici Syndr (1999). 2005;40(2):121–31.CrossRefGoogle Scholar
  15. 15.
    FRAM Study Investigators. Fat Distribution in Women with HIV Infection. J Acquir Immune Defic Syndr Hum Retrovirol. 2006;42(5):562–71.CrossRefGoogle Scholar
  16. 16.
    Tien PC, Cole SR, Williams CM, et al. Incidence of lipoatrophy and lipohypertrophy in the women's interagency HIV study. J Acquir Immune Defici Syndr (1999). 2003;34(5):461–6.CrossRefGoogle Scholar
  17. 17.
    Mallon PW, Miller J, Cooper DA, Carr A. Prospective evaluation of the effects of antiretroviral therapy on body composition in HIV-1-infected men starting therapy. AIDS (London, England). 2003;17(7):971–9.CrossRefGoogle Scholar
  18. 18.
    Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003;289(22):2978–82.PubMedCrossRefGoogle Scholar
  19. 19.
    Grunfeld C. Dyslipidemia and its Treatment in HIV Infection. Top HIV Med. 2010;18(3):112–8.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Bonfanti P, De Socio GV, Ricci E, et al. The feature of Metabolic Syndrome in HIV naive patients is not the same of those treated: results from a prospective study. Biomed Pharmacother. 2012;66(5):348–53.PubMedCrossRefGoogle Scholar
  21. 21.
    Freitas P, Carvalho D, Souto S, et al. Impact of Lipodystrophy on the prevalence and components of metabolic syndrome in HIV-infected patients. BMC Infect Dis. 2011;11:246.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Jacobson DL, Tang AM, Spiegelman D, et al. Incidence of metabolic syndrome in a cohort of HIV-infected adults and prevalence relative to the US population (National Health and Nutrition Examination Survey). J Acquir Immune Defici Syndr (1999). 2006;43(4):458–66.CrossRefGoogle Scholar
  23. 23.
    Palacios R, Santos J, Gonzalez M, Ruiz J, Marquez M. Incidence and prevalence of the metabolic syndrome in a cohort of naive HIV-infected patients: prospective analysis at 48 weeks of highly active antiretroviral therapy. Int J STD AIDS. 2007;18(3):184–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Ramirez-Marrero FA, De Jesus E, Santana-Bagur J, Hunter R, Frontera W, Joyner MJ. Prevalence of cardiometabolic risk factors in Hispanics living with HIV. Ethn Dis. 2010;20(4):423–8.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Wand H, Calmy A, Carey DL, et al. Metabolic syndrome, cardiovascular disease and type 2 diabetes mellitus after initiation of antiretroviral therapy in HIV infection. AIDS (London, England). 2007;21(18):2445–53.CrossRefGoogle Scholar
  26. 26.
    Mangili A, Jacobson DL, Gerrior J, Polak JF, Gorbach SL, Wanke CA. Metabolic syndrome and subclinical atherosclerosis in patients infected with HIV. Clin Infect Dis. 2007;44(10):1368–74.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Mondy K, Overton ET, Grubb J, et al. Metabolic syndrome in HIV-infected patients from an urban, midwestern US outpatient population. Clin Infect Dis. 2007;44(5):726–34.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Beltran-Sanchez H, Harhay MO, Harhay MM, McElligott S. Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999-2010. J Am Coll Cardiol. 2013;62(8):697–703.PubMedCrossRefGoogle Scholar
  29. 29.
    Marquez-Sandoval F, Macedo-Ojeda G, Viramontes-Horner D, Fernandez Ballart JD, Salas Salvado J, Vizmanos B. The prevalence of metabolic syndrome in Latin America: a systematic review. Public Health Nutr. 2011;14(10):1702–13.PubMedCrossRefGoogle Scholar
  30. 30.
    Worm SW, Sabin CA, Reiss P, et al. Presence of the metabolic syndrome is not a better predictor of cardiovascular disease than the sum of its components in HIV-infected individuals: data collection on adverse events of anti-HIV drugs (D:A:D) study. Diabetes Care. 2009;32(3):474–80.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Nicholaou MJ, Martinson JJ, Abraham AG, et al. HAART-associated dyslipidemia varies by biogeographical ancestry in the multicenter AIDS cohort study. AIDS Res Hum Retrovir. 2013;29(6):871–9.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Krishnan S, Schouten JT, Atkinson B, et al. Metabolic syndrome before and after initiation of antiretroviral therapy in treatment-naive HIV-infected individuals. J Acquir Immune Defici Syndr (1999). 2012;61(3):381–9.CrossRefGoogle Scholar
  33. 33.
    Bagdade JD, Lane JT, Subbaiah PV, Otto ME, Ritter MC. Accelerated cholesteryl ester transfer in noninsulin-dependent diabetes mellitus. Atherosclerosis. 1993;104(1–2):69–77.PubMedCrossRefGoogle Scholar
  34. 34.
    Pownall HJ, Brauchi D, Kilinc C, et al. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins. Atherosclerosis. 1999;143(2):285–97.PubMedCrossRefGoogle Scholar
  35. 35.
    Tall AR. Plasma cholesteryl ester transfer protein. J Lipid Res. 1993;34(8):1255–74.PubMedGoogle Scholar
  36. 36.
    Vu CN, Ruiz-Esponda R, Yang E, et al. Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: further evidence for a unique form of metabolic syndrome in HIV patients. Metab Clin Exp. 2013;62(7):1014–20.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Serraino D, Bruzzone S, Zucchetto A, et al. Elevated risks of death for diabetes mellitus and cardiovascular diseases in Italian AIDS cases. AIDS Res Ther. 2010;7:11.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Jarrett OD, Wanke CA, Ruthazer R, Bica I, Isaac R, Knox TA. Metabolic syndrome predicts all-cause mortality in persons with human immunodeficiency virus. AIDS Patient Care STDS. 2013;27(5):266–71.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Kaplan RC, Kingsley LA, Gange SJ, et al. Low CD4+ T-cell count as a major atherosclerosis risk factor in HIV-infected women and men. AIDS (London, England). 2008;22(13):1615–24.CrossRefGoogle Scholar
  40. 40.
    Brown TT, Cole SR, Li X, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005;165(10):1179–84.PubMedCrossRefGoogle Scholar
  41. 41.
    Tien PC, Schneider MF, Cole SR, et al. Antiretroviral therapy exposure and incidence of diabetes mellitus in the Women's Interagency HIV Study. AIDS (London, England). 2007;21(13):1739–45.CrossRefGoogle Scholar
  42. 42.••
    Rasmussen LD, Mathiesen ER, Kronborg G, Pedersen C, Gerstoft J, Obel N. Risk of diabetes mellitus in persons with and without HIV: a Danish nationwide population-based cohort study. PLoS One. 2012;7(9):e44575. Large population based study of DM risk in HIV-infected adults and uninfected adults that found higher DM risk in HIV in the period 1996-1998, but lower risk in the period 1999-2010 suggesting that newer ART might be less metabolically toxic.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    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 Defici Syndr (1999). 2007;45(1):66–71.CrossRefGoogle Scholar
  44. 44.
    Ledergerber B, Furrer H, Rickenbach M, et al. Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV Cohort Study. Clin Infect Dis. 2007;45(1):111–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Butt AA, McGinnis K, Rodriguez-Barradas MC, et al. HIV infection and the risk of diabetes mellitus. AIDS (London, England). 2009;23(10):1227–34.CrossRefGoogle Scholar
  46. 46.
    Tien PC, Schneider MF, Cox C, Karim R, Cohen M, Sharma A, et al. Association of HIV Infection with incident diabetes mellitus: impact of using hemoglobin A1C as a criterion for diabetes. J Acquir Immune Defic Syndr. 2012;61(3):334–40.Google Scholar
  47. 47.
    Tripathi A, Liese AD, Jerrell JM, et al. Incidence of diabetes mellitus in a population-based cohort of HIV-infected and non-HIV-infected persons: the impact of clinical and therapeutic factors over time. Diabet Med: J Br Diabet Assoc. 2014.Google Scholar
  48. 48.
    Grunfeld C. Insulin resistance in HIV infection: drugs, host responses, or restoration to health? Top HIV Med. 2008;16(2):89–93.PubMedGoogle Scholar
  49. 49.
    Tien PC, Schneider MF, Cole SR, et al. Antiretroviral therapy exposure and insulin resistance in the Women's Interagency HIV study. J Acquir Immune Defici Syndr (1999). 2008;49(4):369–76.CrossRefGoogle Scholar
  50. 50.
    Brown TT, Li X, Cole SR, et al. Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study. AIDS (London, England). 2005;19(13):1375–83.CrossRefGoogle Scholar
  51. 51.
    ADA. Diagnosis and Classification of diabetes mellitus. Diabetes Care. 2010;33(1S):S62–69S.Google Scholar
  52. 52.
    Hu FB, Meigs JB, Li TY, Rifai N, Manson JE. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004;53(3):693–700.PubMedCrossRefGoogle Scholar
  53. 53.
    Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286(3):327–34.PubMedCrossRefGoogle Scholar
  54. 54.
    Spranger J, Kroke A, Mohlig M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes. 2003;52(3):812–7.PubMedCrossRefGoogle Scholar
  55. 55.
    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(10):2244–9.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143–421.Google Scholar
  57. 57.
    Lichtenstein KA, Armon C, Buchacz K, et al. Provider compliance with guidelines for management of cardiovascular risk in HIV-infected patients. Prev Chron Dis. 2013;10:E10.Google Scholar
  58. 58.
    Ajani UA, Ford ES. Has the risk for coronary heart disease changed among U.S. adults? J Am Coll Cardiol. 2006;48(6):1177–82.PubMedCrossRefGoogle Scholar
  59. 59.••
    Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Int Med. 2013;173(8):614–22. Large study of U.S. based-veterans that found that HIV infection is associated with a 50% greater risk of acute myocardial infection even after controlling for Framingham risk factors, comorbidities, and substance use.CrossRefGoogle Scholar
  60. 60.
    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(5):491–501.PubMedCrossRefGoogle Scholar
  61. 61.
    Law MG, Friis-Moller N, El-Sadr WM, et al. The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D Study. HIV Med. 2006;7(4):218–30.PubMedCrossRefGoogle Scholar
  62. 62.
    Wolf PA, D'Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke; J Cereb Circ. 1991;22(3):312–8.CrossRefGoogle Scholar
  63. 63.••
    Mateen FJ, Post WS, Sacktor N, et al. Long-term predictive value of the Framingham Risk Score for Stroke in HIV-positive vs HIV-negative men. Neurology. 2013;81(24):2094–102. Large prospective observational cohort study of men from the Multicenter AIDS Cohort Study that found that HIV-uninfected men had a higher 10-year FRS-Stroke score (FRS-S) than HIV-infected men, but HIV-infected had two-fold higher incidence of first-ever strokes and were on average younger than the HIV-uninfected men who had first-ever strokes.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Ortiz G, Koch S, Romano JG, Forteza AM, Rabinstein AA. Mechanisms of ischemic stroke in HIV-infected patients. Neurology. 2007;68(16):1257–61.PubMedCrossRefGoogle Scholar
  65. 65.
    Kakinami L, Block RC, Adams MJ, Cohn SE, Maliakkal B, Fisher SG. Risk of cardiovascular disease in HIV, hepatitis C, or HIV/hepatitis C patients compared to the general population. Int J Clin Pract. 2013;67(1):6–13.PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Stein JH, Brown TT, Ribaudo HJ, et al. Ultrasonographic measures of cardiovascular disease risk in antiretroviral treatment-naive individuals with HIV infection. AIDS (London, England). 2013;27(6):929–37.CrossRefGoogle Scholar
  67. 67.
    Currier JS, Kendall MA, Henry WK, et al. Progression of carotid artery intima-media thickening in HIV-infected and uninfected adults. AIDS (London, England). 2007;21(9):1137–45.CrossRefGoogle Scholar
  68. 68.
    Currier JS, Kendall MA, Zackin R, et al. Carotid artery intima-media thickness and HIV infection: traditional risk factors overshadow impact of protease inhibitor exposure. AIDS (London, England). 2005;19(9):927–33.CrossRefGoogle Scholar
  69. 69.
    Nery MW, Martelli CM, Silveira EA, et al. Cardiovascular risk assessment: a comparison of the Framingham, PROCAM, and DAD equations in HIV-infected persons. Sci World J. 2013;2013:969281.CrossRefGoogle Scholar
  70. 70.
    Edwards-Jackson N, Kerr S, Tieu H, et al. Cardiovascular risk assessment in persons with HIV infection in the developing world: comparing three risk equations in a cohort of HIV-infected Thais. HIV Med. 2011;12(8):510–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Clinical PharmacyUniversity of CaliforniaSan FranciscoUSA
  2. 2.Northern California Institute for Research and EducationSan FranciscoUSA
  3. 3.Department of MedicineUniversity of CaliforniaSan FranciscoUSA
  4. 4.Department of Veterans Affairs Medical CenterMedical ServiceSan FranciscoUSA

Personalised recommendations