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Lipids, metabolic syndrome, and risk factors for future cardiovascular disease among HIV-infected patients

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Abstract

The availability of potent combination antiretroviral therapy has changed the long-term prognosis for people living with HIV/AIDS. There is increasing concern, however, about the effect of HIV therapy on lipid disorders and subsequent development of coronary artery disease. Virtually all classes of antiretroviral drugs have been associated with some aspect of atherogenic changes in the lipid profiles. This article reviews the current literature on HIV-associated dyslipidemias and the metabolic syndrome, their potential effect on future coronary heart disease, and reviews strategies for management.

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References and Recommended Reading

  1. United States Department of Health and Human Services: Update: Mortality Attributable to HIV Infection Among Persons Aged 25–44 Years—United States, 1994. Morb Mortal Wkly Rep 1996, 45:121–125.

    Google Scholar 

  2. United States Department of Health and Human Services: Update: Trends in AIDS Incidence, Deaths, and Prevalence—United States, 1996. Morb Mortal Wkly Rep 1997, 46:165–173.

    Google Scholar 

  3. Palella FJ Jr, Delaney KM, Moorman AC, et al.: Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection. N Engl J Med 1998, 338:853–860.

    Article  PubMed  Google Scholar 

  4. Riddler SA, Smit E, Cole SR, et al.: Impact of HIV infection and HAART on serum lipids in men. JAMA 2003, 289:2978–2982. This is a prospective study describing the changes in serum cholesterol levels associated with HIV infection and subsequent antiretroviral medication exposure.

    Article  PubMed  CAS  Google Scholar 

  5. Grunfeld C, Pang M, Doerrler W, et al.: Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab 1992, 74:1045–1052.

    Article  PubMed  CAS  Google Scholar 

  6. Behrens G, Dejam A, Schmidt H, et al.: Impaired glucose tolerance, beta cell function, and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS 1999, 13:F6370.

    Article  Google Scholar 

  7. Calza L, Manfredi R, Farneti B, et al.: Incidence of hyperlipidaemia in a cohort of 212 HIV-infected patients receiving a protease inhibitor-based antiretroviral therapy. Int J Antimicrob Agents 2003, 22:54–59.

    Article  PubMed  CAS  Google Scholar 

  8. Periard D, Telenti A, Sudre P, et al.: Atherogenic dyslipidemia in HIV-infected Individuals treated with protease inhibitors. The Swiss HIV Cohort Study. Circulation 1999, 100:700–705.

    PubMed  CAS  Google Scholar 

  9. Domingo P, Sambeat MA, Perez A, et al.: Effect of protease inhibitors on apolipoprotein B levels and plasma lipid profile in HIV-1-infected patients on highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2003, 33:114–116.

    PubMed  Google Scholar 

  10. Manfredi R, Chiodo F: Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate. J Infect 2001, 42:181–188.

    Article  PubMed  CAS  Google Scholar 

  11. Fontas E, van Leth F, Sabin CA, et al.: F Lipid profiles in HIVinfected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect Dis 2004, 189(6):1056–1074. This paper provides a comparison of levels of serum triglycerides, total cholesterol, low density lipopoproteins, and high-density lipoproteins among HIV-infected patients receiving different antiretroviral therapy regimens.

    Article  PubMed  CAS  Google Scholar 

  12. Walmsley S, Bernstein B, King M, et al.: Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med 2002, 346:2039–2046.

    Article  PubMed  CAS  Google Scholar 

  13. Cahn PE, Gatell JM, Squires K, et al.: Atazanavir—a once-daily HIV protease inhibitor that does not cause dyslipidemia in newly treated patients: results from two randomized clinical trials. J Int Assoc Physicians AIDS Care (Chic Ill) 2004, 3:92–98.

    Article  Google Scholar 

  14. Squires K, Lazzarin A, Gatell JM, et al.: Comparison of oncedaily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV. J Acquir Immune Defic Syndr 2004, 36:1011–1019.

    Article  PubMed  CAS  Google Scholar 

  15. van Leth F, Phanuphak P, Stroes E, et al.: Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral-Therapy-Naive Patients Infected with HIV-1. PLoS Med 2004, 1:e19.

    Article  PubMed  CAS  Google Scholar 

  16. van der Valk JM, Kastelein JJ, Murphy RL, et al.: Nevirapinecontaining antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile. AIDS 2001, 15:2407–2414.

    Article  PubMed  Google Scholar 

  17. Clotet B, van der Valk M, Negredo E, Reiss P: Impact of nevirapine on lipid metabolism. J Acquir Immune Defic Syndr 2003, 34 (Suppl:1):S79–84.

    PubMed  CAS  Google Scholar 

  18. Fisac C, Virgili N, Ferrer E, et al.: A comparison of the effects of nevirapine and nelfinavir on metabolism and body habitus in antiretroviral-naive human immunodeficiency virusinfected patients: a randomized controlled study. J Clin Endocrinol Metab 2003, 88:5186–5192.

    Article  PubMed  CAS  Google Scholar 

  19. Gallant JE, Staszewski S, Pozniak AL, et al.: Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004, 292:191–201.

    Article  PubMed  CAS  Google Scholar 

  20. Hellerstein MK, Grunfeld C, Wu K, et al.: Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. Clin Endocrinol Metab 1993, 76:559–565.

    Article  CAS  Google Scholar 

  21. Petit JM, Duong M, Florentin E, et al.: Increased VLDL-apoB and IDL-apoB production rates in nonlipodystrophic HIVinfected patients on a protease inhibitor-containing regimen: a stable isotope kinetic study. J Lipid Res 2003, 44:1692–1697.

    Article  PubMed  CAS  Google Scholar 

  22. Malmstrom R, Packard CJ, Caslake M, et al.: Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia 1997, 40:454–462.

    Article  PubMed  CAS  Google Scholar 

  23. Liang JS, Distler O, Cooper DA, et al.: HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia. Nat Med 2001, 7:1327–1331.

    Article  PubMed  CAS  Google Scholar 

  24. Brinkman K, ter Hofstede HJ, Burger DM, et al.: Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 1998, 12:1735–1744.

    Article  PubMed  CAS  Google Scholar 

  25. Tabib A, Greenland T, Mercier I, et al.: Coronary lesions in young HIV-positive subjects at necropsy. Lancet 1992, 340:730.

    Article  PubMed  CAS  Google Scholar 

  26. Maggi P, Serio G, Epifani G, et al.: Premature lesions of the carotid vessels in HIV-1-infected patients treated with protease inhibitors. AIDS 2000, 14:F123–128.

    Article  PubMed  CAS  Google Scholar 

  27. Klein D, Hurley L, Quesenberry CP Jr, Sidney S: Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acquir Immune Defic Syndr 2002, 30:471–477.

    PubMed  CAS  Google Scholar 

  28. Currier J, Taylor A, Boyd F, et al.: Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr 2003, 33:506–512.

    PubMed  Google Scholar 

  29. Holmberg SD, Moorman AC, Williamson JM, et al.: Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet 2002, 360:1747–1748.

    Article  PubMed  CAS  Google Scholar 

  30. Friis-Moller N, Sabin C, Weber R, et al.: Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003, 349:1993–2003. This is an observational study that examines the effect of exposure to antiretroviral medication on the risk of myocardial infarction among HIV-infected patients on HAART.

    Article  PubMed  Google Scholar 

  31. Stein JH: Managing Cardiovascular Risk in Patients with HIV Infection. J Acquir Immune Defic Syndr 2005, 38:115–123.

    Article  PubMed  Google Scholar 

  32. Gil P, de Gorgolas M, Estrada V, et al.: Long-term efficacy and safety of protease inhibitor switching to nevirapine in HIVinfected patients with undetectable virus load. Clin Infect Dis 2004, 39:1024–1029.

    Article  PubMed  CAS  Google Scholar 

  33. Keiser PH, Sension MG, Dejesus E, et al.: Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment. BMC Infect Dis 2005, 5:2.

    Article  PubMed  CAS  Google Scholar 

  34. Martinez E, Azuaje C, Antela A, et al.: Effects of switching to ritonavir-boosted Atazanavir on HIV-infected patients receiving anti-retroviral therapy with hyperlipidemia [abstract no. 850]. Paper presented at the 12th Conference on Retroviruses and Opportunistic Infections. Boston, Feb 22–25, 2005.

  35. Sension M, Grinsztejn B, Molina J, et al.: A1424067: Improvement in lipid profiles after 12 weeks of switching to Atazanavir from boosted or unboosted protease inhibitors in patients with no previous PI virologic failure and hyperlipidemia at baseline [abstract no. 858]. Paper presented at the 12th Conference on Retroviruses and Opportunistic Infections. Boston, Feb 22–25, 2005.

  36. Carr A, Thorisdottir A, Samaras K, et al.: Reversibility of protease inhibitor (PI) lipodystrophy syndrome on stopping PIs or switching to nelfinavir [abstract no. 668]. Paper presented at the 6th Conference on Retroviruses and Opportunistic Infections. Chicago, Jan 31–Feb 4, 1999.

  37. Negredo E, Ribalta J, Paredes R, et al.: Reversal of atherogenic lipoprotein profile in HIV-1 infected patients with lipodystrophy after replacing protease inhibitors by nevirapine. AIDS 2002, 16:1383–1389.

    Article  PubMed  CAS  Google Scholar 

  38. Dubé MP, Stein JH, Aberg JA, et al.: Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis 2003, 37:613–627. This paper provides guidelines for evaluation and management of dyslipidemia in HIV-infected patients on HAART.

    Article  PubMed  Google Scholar 

  39. Rubins HB, Robins SJ, Collins D, et al.: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 1999, 341:4108.

    Article  Google Scholar 

  40. Gould AL, Rossouw JE, Santanello NC, et al.: Cholesterol reduction yields clinical benefit. Impact of statin trials. Circulation 1998, 97:94652.

    Google Scholar 

  41. Henry K, Melroe H, Huebesch J, et al.: Atorvastatin and gemfibrozil for protease-inhibitor-related lipid abnormalities. Lancet 1998, 352:10312.

    Google Scholar 

  42. Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al.: Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS 2002, 16:569–577.

    Article  PubMed  CAS  Google Scholar 

  43. Executive summary of the 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). JAMA 2001, 285:2486-2497.

    Google Scholar 

  44. Ford ES, Giles WH, Dietz WH: Prevalence of the metabolic syndrome among US adults: findings from the third national health and nutrition examination survey. JAMA 2002, 287:356–359.

    Article  PubMed  Google Scholar 

  45. Kahn CR, Flier JS, Bar RS, et al.: The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med 1976, 294:739–745.

    Article  PubMed  CAS  Google Scholar 

  46. Miranda PJ, DeFronzo RA, Califf RM, Guyton JR: Metabolic syndrome: definition, pathophysiology, and mechanisms. Am Heart J 2005, 149:33–45.

    Article  PubMed  CAS  Google Scholar 

  47. UK Prospective Diabetes Study (UKPDS) Group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998, 352:837–853.

    Article  Google Scholar 

  48. Kelley DE, Mandarino LJ: Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 2000, 49:677–683.

    Article  PubMed  CAS  Google Scholar 

  49. Jerico C, Knobel H, Montero M, et al.: Metabolic syndrome among HIV-infected patients: prevalence, characteristics, and related factors. Diabetes Care 2005, 28:132–137.

    Article  PubMed  Google Scholar 

  50. Ninomiya JK, L’Italien G, Criqui MH, et al.: Association of the metabolic syndrome with history of myocardial infarction and stroke in the Third National Health and Nutrition Examination Survey. Circulation 2004 Jan, 109:42–46.

    PubMed  Google Scholar 

  51. McNeill AM, Rosamond WD, Girman CJ, et al.: Prevalence of coronary heart disease and carotid arterial thickening in patients with the metabolic syndrome (The ARIC Study). Am J Cardiol 2004, 94:1249–1254.

    Article  PubMed  Google Scholar 

  52. McNeill AM, Rosamond WD, Girman CJ, et al.: The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care 2005, 28:385–390.

    Article  PubMed  Google Scholar 

  53. Hurwitz BE, Klimas NG, Llabre MM, et al.: HIV, metabolic syndrome X, inflammation, oxidative stress, and coronary heart disease risk: role of protease inhibitor exposure. Cardiovasc Toxicol 2004, 4:303–316.

    Article  PubMed  CAS  Google Scholar 

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Umeh, O.C., Currier, J.S. Lipids, metabolic syndrome, and risk factors for future cardiovascular disease among HIV-infected patients. Curr HIV/AIDS Rep 2, 132–139 (2005). https://doi.org/10.1007/s11904-005-0006-6

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