The use of Human Immunodeficiency Virus (HIV) protease inhibitors as part of the Highly Active Antiretroviral Therapy (HAART) is associated with atherogenic dyslipoproteinemia, insulin resistance, hypertension and endothelial dysfunction, all of which contribute to premature coronary heart disease. These abnormalities appear to be associated with an increase in cardiovascular events in HIV-infected patients. Beneficial metabolic effects of anti-diabetic agents used in HIV-infected patients have been reported. The thiazolidinediones (TZDs), a new group of antidiabetic drugs, may modulate the proliferative and inflammatory cascades involved in atherosclerosis. Thus, an increasing totality of evidence suggests that TZDs may represent a unique and powerful research tool to find a common denominator underlying the pathophysiology and treatment of the metabolic cardiovascular risk factors associated with HIV infection.
1. Passalaris JD, Sepkowitz KA, Glesby MJ. Coronary artery disease and human immunodeficiency virus infection. Clin Infect Dis31:787-797.
2.
2. Chi D, Henry J, Kelley J, et al. The effects of HIV infection on endothelial function. Endothelium7(4):223-242, 2000.
3.
3. Periard D, Telenti A, Sudre P, et al. Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. The Swiss HIV cohort study. Circulation100(7):700-705, 1999.
4.
4. Stein JH, Klein MA, Bellehumeur JL. Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation104(3):257-262, 2001.
5.
5. Vigoroux C, Gharakhanian S, Salhi Y, et al. Diabetes, insulin resistance and dyslipidemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART). Diab Metab25(3):225-232, 1999.
6.
6. Walli R, Herfort 0, Michl GM, et al. Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1-infect-ed patients. AIDS12(15):F167-173, 1998.
7.
7. Rickerts V, Brodt H, Staszewski S, Stille W. Incidence of myocardial infarctions in HIV-infected patients between 1983 and 1998: The Frankfurt HIV-cohort study. Eur J Med Res5(8):329-333, 2000.
8.
8. Holmberg S, Moorman A, Tong T, Ward D, Wood K, Greenberg AE, et al. Protease inhibitor use and adverse cardiovascular outcomes in ambulatory HIV patients [abstract 91]. In: 9th Conference on Retroviruses and Opportunistic Infections: Programs and abstracts (Seattle, WA). Alexandria, VA: Foundation for Retroviruses and Human Health, 2002.
9.
9. Friedl AC, Jost CH, Schalcher C, Amann FW, Flepp M, Jenni R, Linka A, Weber R. Acceleration of confirmed coronary artery disease among HIV-infected patients on potent antiretroviral therapy. AIDS14(17):2790-2792, 2000.
10.
10. Wilson PW, Kannel WB, Silbershatz H, D'Agostino RB.Clustering of metabolic factors and coronary heart disease. Arch Int Med159(10):1104-1109, 1999.
11.
11. Komers R, Vrana A.Thiazolidinediones-tools for the research of metabolic syndrome X. Physiol Res47(4):215-225, 1998.
12.
12. Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, et al. Nonhypoglycemic effects of thiazolidinediones. Ann Int Med134(1):61-71, 2001.
13.
13. Berger J, Moller DE. The mechanisms of action of PPARs. Ann Rev Med53:409-435.
14.
14. Ziouzenkova 0, Perrey S, Marx N, et al. Peroxisome Proliferator-activated Receptors. Cuff Ather Rep4(1): 59-64, 2002.
15.
15. Fukunaga Y, Itoh H, Doi K, Tanaka T, et al. Thiazolidinediones, peroxisome proliferator-activated receptor gamma agonists, regulate endothelial cell growth and secretion of vasoactive peptides. Atherosclerosis158(1): 113-119, 2001.
16.
16. Takagi T, Akasaka T, Yamamuro A, et al. Troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus. J Am Coll Cardiol36(5):1529-1535, 2000.
17.
17. Koshiyama H, Shimono D, Kuwamura N, et al. Rapid communication: Inhibitory effect of pioglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endo Metab86(7):3452-3456, 2001.
18.
18. Hattori Y, Hattori S, Kasai K. Troglitazone upregulates nitric oxide synthesis in vascular smooth muscle cells. Hypertension33(4):943-948, 1999.
19.
19. Walli R, Michl GM, Muhlbayer D, Brinkmann L, Goebel FD. Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated dia-betes mellitus. Res Exp Med199(5):253-262, 2000.
20.
20. Kato K, Satoh H, Endo Y, Yamada D. Thiazolidinediones down-regulate plasminogen inhibitor type 1 expression in human vascular endothelial cells: A possible role for PPARgamma in endothelial function. Biochem Biophys Res Comm258(2):431-435, 1999.
21.
21. Hirose H, Kawai T, Yamamoto Y, et al. Effects of pioglita-zone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes. Metab Clin Exp51(3):314-317, 2002.
22.
22. Goud C, Pitt B, Webb RC, Richey JM.Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings. Am J Physiol275(5 Pt 1):E882-887, 1998.
23.
23. Gabriely I, Wozniak R, Hawkins M, Shamoon H. Troglitazone amplifies counterregulatory responses to hypoglycemia in nondiabetic subjects. J Clin Endo Metab86(2):521-528, 2001.
24.
24. Hadigan C, Corcoran C, Basgoz N, Davis B, Sax P, Grinspoon S. Metformin in the treatment of HIV lipodys-trophy syndrome: A randomized controlled trialJAMA. 284(4):472-477, 2000.
