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Metabolic complications and antiretroviral therapy


Authors: S. Snopková;  K. Povolná;  P. Husa
Authors‘ workplace: Přednosta: prof. MUDr. Petr Husa, CSc. ;  Klinika infekčních chorob Lékařské fakulty MU a FN Brno-Bohunice
Published in: Prakt. Lék. 2008; 88(11): 630-634
Category: Reviews

Overview

The clinical course of HIV/AIDS has been substantially modified by improved therapy in recent years. The progress of the disorder has changed – today it is a chronic disease with a long course. Long-term cART (combination antiretroviral therapy) significantly affects the subsequent progress of the disease but produces adverse metabolic changes – dyslipidaemia, insulin resistance, coagulation changes, antropometric changes – lipodystrophy, lipoatrophy and so on. The most prominent clinical signs have been defined as a new syndrome – “HIV-associated lipodystrophy syndrome”. HIV-associated lipodystrophy syndrome includes metabolic alterations (dyslipidaemia, insulin resistance) and abnormal fat redistribution. The paper discusses the possible pathogenesis and potential mechanisms of the metabolic complications related to cART – defective activation and nuclear translocation SREBP-1, inhibition of GLUT 4, proteasomal inhibition and mitochondrial toxicity. But current data indicate a rather multifactorial pathogenesis where HIV infection, its therapy, and patient-related factors are major contributors. The paper discusses the possible impact of cART on cardiovascular risk and the possibilities of hypolipidaemic therapy in HIV-positive patients.

Key words:
HIV, cART, dyslipidaemia, insulin resistance, fat redistribution, lipodystrophy syndrome, cardiovascular risk.


Sources

1. Anderlová, K., Haluzík, M. Tuková tkáň a inzulinová rezistence. DMEV 2005, 2, s. 87-96.

2. Balasubramanyam, A., Sekhar, R.V., Jahoor, P. et al. Pathophysiology of dyslipidemia and increased cardiovascular risk in HIV lipodystrophy: a model of „systemic steatosis“. Curr. Opin. Lipidol. 2004, 15, p. 59-67.

3. Bartlett, J.G., Gallant, J.E. Medical management of HIV infection 2007. Johns Hopkins University School of Medicine Baltimore, Health Publishing Business Group 2007, p. 93-98.

4. Ben-Romano, R., Rudich, A., Torok, D. et al. Agent and cell-type specifity in the induction of insulin resistance by HIV protease inhibitors. AIDS 2003, 17, p. 23-32.

5. Bozzette, S.A., Ake, C.F., Tam, H.K. et al. Cardiovascular and cerebrovascular events in patients treated for HIV infection. N. Engl. J. Med. 2003, 348, p. 702-710.

6. Braitstein, P., Yip, B., Heath, K.V. et al. Interventional cardiovascular procedures among HIV-infected individuals on antiretroviral therapy 1995-2000. AIDS 2003, 17, p. 2071-2075.

7. Calza, L., Manfredi, R., Colangelli, V. et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy fort he management of dyslipidaemia. AIDS 2005, 19, p. 1051-1058.

8. Carr, A., Grund, B., Neuhaus, J. et al. Asymptomatic myocardial ischaemia in HIV-infected adults. AIDS 2008, 22, p. 257-267.

9. Carr, A., Law, M. An objective lipodystrophy severity grading scale derived from the lipodystrophy case definition score. J. Acquir. Immune Defic. Syndr. 2003, 33, p. 571-576.

10. Chaloupka, V. Ezetimib - terapeutický přínos v léčbě dyslipidemií. Cor. Vasa 2005, 47, s. 315-318.

11. Chene, G., Angelini, E., Cotte, L. et al. Role of long-term nucleoside-analogue therapy in lipodystrophy and metabolic disorders in human immunodeficiency virus-infected patients. Clin. Infect. Dis. 2002, 34, p. 649-657.

12. Currier, J.S., Kendall, M.A., Henry, W.K. et al. Progression of carotid artery intima-media thickening in HIV-infected and uninfected adults. AIDS 2007, 21, p. 1137-1145.

13. Češka, R. Jak dosáhnout cílových hodnot LDL-cholesterolu? Místo ezetimibu v moderní léčbě hypercholesterolemie. Cor. Vasa 2004, 46, s. 452-456.

14. De Gaetano Donati, K., Rabagliati, R., Iacoviello, L., Cauda, R. HIV infection, HAART, and endothelial adhesion molecules: current perspectives. Lancet Infect. Dis. 2004, 4, p. 213-222.

15. Dreschler, H., Powderly, W.G. Switching effective antiretroviral therapy: a review. Clin. Infect. Dis. 2002, 35, p. 1219-1230.

16. Dubé, M.P., Stein, J.H., Aberg, J.A. et al. Giudelines for the evaluation and management of dyslipidemia in human immunodeficiency virus – infected adults receiving antiretroviral therapy: recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin. Infect. Dis. 2003, 37, p. 613-627.

17. Galli, M. Cardiovascular disease in HIV: The risks in perspective. In: Program and Abstracts of the scientific symposium on the management of HIV infection. Marrakech 2005, p. 12-13.

18. Gan, S.K., Samaras, K., Thompson, C.H. et al. Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy. Diabetes 2002, 51, p. 3163-3169.

19. Gerard, Y., Yazdanpanah, Y., Ajana, F., et al. Use of stavudine is associated with a high risk of severe hyperlactataemia in black women. Antiv. Ther. 2005, 10, p. 42-43.

20. Grinspoon, S., Carr, A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N. Engl. J. Med. 2005, 352, p.48-62.

21. Haugaard, S.B., Andersen, O., Dela, F. et al. Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells. Eur. Endocrinol. 2005, 152, p. 103-112.

22. Joly, V., Flandre, P., Meiffredy, S. et al. Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial. AIDS 2002, 16, p. 2447-2454.

23. Klein, D., Hurley, L.B., Quesenberry, C.P. et al. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J. Acquir. Immune Defic. Syndr. 2002, 30, p. 471-477.

24. Konvalinka, J., Machala, L. Terapie AIDS po dvaceti letech. Vesmír 2001, 6, s. 332-340.

25. Lactic Acidosis International Study Group. Risk factors for lactic acidosis and severe hyperlactataemia in HIV-1-infected adults exposed to antiretroviral therapy. AIDS 2007, 21, p. 2455-2464.

26. Lowell, B.B., Shulman, G.I. Mitochondrial dysfunction and type 2 diabetes. Science 2005, 307, p. 384-387.

27. Machala, L. Enfuvirtid. Klin. mikrobiol. inf. lék. 2004, 3, s. 114-117.

28. Mallon, P.W., Unemori, P., Sedwell, R. et al. In vivo, nucleoside reverse/transcriptase inhibitors alter expression of both mitochondrial and lipid metabolism genes in the absence of depletion of mitochondrial DNA. J. Infect. Dis. 2005, 191, p. 1686-1696.

29. Martin, A., Smith, D.E., Carr, A. 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, p. 1029-1036.

30. Mary-Krause, M., Cotte, L., Simon, A. et al. Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS 2003, 17, p. 2479-2486.

31. McDermott, A.Y., Terrin, N., Wanke, C. et al. CD4+ cell count, viral load, and highly active antiretroviral therapy use are independent predictors of body composition alterations in HIV-infected adults: a longitudinal study. Clin. Infect. Dis. 2005, 41, p. 1662-1670.

32. Meininger, G., Hadigan, C., Laposata, M. et al. Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution. Metabolism. 2002, 51, p. 260-266.

33. Miserez, A.R., Muller, P.Y., Spaniol, V. Indinavir inhibits sterol-regulatory element-binding protein-1c-dependent lipoprotein lipase and fatty acid synthase gene activations. AIDS 2002, 16, p. 1587-1594.

34. Miserez, A.R. Principles of lipoprotein metabolism: the role of the SREBPs. E. J. Med. Res. 2003, 8, Suppl II, p. 5-6.

35. Nolan, D. Metabolic complications associated with HIV protease inhibitor therapy. Drugs 2003, 63, p. 2555-2574.

36. Nolan, D., Mallal, S. Complications associated with NRTI therapy: update on clinical features and possible pathogenic mechanisms. Antivir. Ther. 2004, 9, p. 849-863.

37. Osborne, T.F. Sterol regulatory element-binding proteins (SREBPs): key regulators of nutritional homeostasis and insulin action. J. Biol. Chem. 2000, 275, p. 32379-32382.

38. Perret, B., Ferrand, C., Bonnet, E. et al. Lipoprotein metabolism in HIV-positive patients. E. J. Med. Res. 2003, 8, Suppl II, p. 6-7.

39. Petit, J.M., Duong, M., Duvillard, L. et al. HIV-1 protease inhibitors induce an increase of triglyceride level in HIV-infected men without modification of insulin sensitivity: a longitudinal study. Horm. Metab. Res. 2000, 32, p. 367-372.

40. Rakotoambinina, B., Medioni, J., Rabian, C. et al. Lipodystrophic syndromes and hyperlipidemia in a cohort of HIV-1-infected patients receiving triple combination antiretroviral therapy with a protease inhibitor. J. Acquir. Immune. Defic. Syndr. 2001, 27, p. 443-449.

41. Ranjit, N., Diez-Roux, A.V., Shea, S. et al. Socioeconomic position, race/ethnicity, and inflammation in the multi-ethnic study of atherosclerosis. Circulation 2007, 116, p. 2383-2390.

42. Roth, V.R., Kravcik, S., Angel, J.B. Development of cervical fat pads following therapy with human immunodeficiency virus type 1 protease inhibitors. Clin. Infect. Dis. 1998, 27, p. 65-67.

43. Rozsypal, H., Staňková, M. Úskalí antiretrovirové terapie. Klin. mikrobiol. inf. lék. 2000, 6, s. 242-249.

44. Rudich, A., Vanounou, S., Reisenberg, K. et al. The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes. Diabetes 2001, 50, p. 1425-1431.

45. Sedláček, D., Staňková, M., Machala, L. et al. Komplexní postup antiretrovirové léčby osob infikovaných virem lidské imunodeficience (HIV) v České republice. Klin. mikrobiol. inf. lék. 2007, 13, 1, s. 28-34.

46. Simon, G.L., Liappis, A.P., Granger, S.L., et al. Antiretroviral therapy-induced changes in lipoprotein subclass phenotype: comparison of protease inhibitor and non-nucleoside reverse transcriptase inhibitor regimens. Antivir. Ther. 2002, 7, L9.

47. Skokanová, V., Staňková, M. Buňky imunitního systému v patogenezi HIV infekce. Klin. mikrobiol. inf. lék. 2005, 11, s. 56-61.

48. Sniderman, A.D., Scantlebury, T., Cianflone, K. Hypertriglyceridemic hyperapoB: the unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus. Ann. Intern. Med. 2001, 135, p. 447-459.

49. Soška, V. Dyslipidemie u metabolického syndromu. Vnitř. Lék. 2005, 1, s. 77-81.

50. Souček, M. Úvod do problematiky metabolického syndromu. Vnitř. Lék. 2005, 1, s. 48-52.

51. Staňková, M., Skokanová, V. Problematika HIV/AIDS - ohlédnutí a perspektivy. Klin. mikrobiol. inf. lék. 2004, 10, s. 56-60.

52. Stein, J.H. Managing cardiovascular risk in patients with HIV infection. J. Acquir. Immune Defic. Syndr. 2005, 38, p. 115-123.

53. Šrámková, D., Kunešová, M., Hainer, V., Bendlová, B. Gen PPAR g ve středu zájmu obezitologů a diabetologů. DMEV 2001, 4, s. 278-286.

54. The Writing Committee of the D:A:D Study Group. Cardio- and cerebrovascular events in HIV-infected persons. AIDS 2004, 13, p. 1811-1817.

55. Van der Valk, M., Bisschop, P.H., Romijn, J.A. et al. Lipodystrophy in HIV-1-positive patients is associated with insulin resistance in multiple metabolic pathways. AIDS 2001, 15, p. 2093-2100.

56. Wand, H., Calmy, A., Carey, D.L., et al. Metabolic syndrome, cardiovascular disease and type 2 diabetes mellitus after initiation of antiretroviral therapy in HIV infection. AIDS 2007, 21, p. 2445-2453.

57. Widimský, J. Problémy s novými a novějšími hypolipidemiky. Cor. Vasa 2008, 50, 6, s. 232-234.

58. Worm, D., Kirk, O., Andersen, O. et al. Clinical lipoatrophy in HIV-1 patients on HAART is not associated with increased abdominal girth, hyperlipidemia nor glucose intolerance. HIV Med. 2002, 3, p. 239-246.

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