Impact of HIV and highly active antiretroviral therapy on leukocyte adhesion molecules, arterial inflammation, dyslipidemia, and atherosclerosis

  • Stacy D. Fisher
    Mid-Atlantic Cardiovascular Associates, Baltimore, MD, USA
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  • Tracie L. Miller
    Department of Pediatrics (D820), Miller School of Medicine at the University of Miami and Holtz Children's Hospital of the University of Miami, Jackson Memorial Medical Center, Medical Campus-MCCD-D820, 1601 NW 12th Avenue, 9th Floor, Miami, FL 33136, USA
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  • Steven E. Lipshultz
    Corresponding author. He is a member of the Sylvester Comprehensive Cancer Center. Tel.: +1 305 243 3993; fax: +1 305 243 3990.
    Department of Pediatrics (D820), Miller School of Medicine at the University of Miami and Holtz Children's Hospital of the University of Miami, Jackson Memorial Medical Center, Medical Campus-MCCD-D820, 1601 NW 12th Avenue, 9th Floor, Miami, FL 33136, USA
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      Highly active antiretroviral therapy (HAART) has greatly extended the lives of people infected with the human immunodeficiency virus (HIV). This reduced risk of early death from opportunistic infections or other sequelae of HIV infection, however, means that other possible causes of death emerge. Myocardial infarction has become a matter of particular concern. Two of the main sources of cardiovascular disease in this population are believed to be vascular inflammation and dyslipidemia. We review the evidence for this hypothesis and discuss the relationship of HIV to vascular inflammation. Current treatment guidelines do not recommend the immediate initiation of HAART unless warranted, potentially allowing long-term, unchecked viral impact on the development of atherosclerosis. Finally, we consider the protease inhibitors traditionally included in HAART regimens and their relationship to the development of dyslipidemia, as well as other classes of antiretrovirals, such as the non-nucleoside reverse transcriptase inhibitors, which might be a better choice for patients with cardiovascular risks. Other strategies, such as pharmacologic, nutritional, and physical activity interventions are discussed. The patients who might benefit most are those in whom the precursors of vascular plaques, such as fatty streak, smooth muscle cell, macrophage, and T-lymphocyte aggregation not yet identified by echocardiographic and biopsy findings have already developed as a result of unchecked viral inflammation and replication.


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        • Fisher S.D.
        • Lipshultz S.E.
        Cardiovascular abnormalities in HIV-infected individuals.
        in: Zipes D.P. Libby P. Bonow R.O. Braunwald E. Braunwald's Heart Disease. A textbook of cardiovascular medicine. 7th ed. Elsevier Saunders, Philadelphia2005: 1719-1730
        • Fisher S.D.
        • Lipshultz S.E.
        Cardiac disease.
        in: Dolin R. Masur H. Saag MS. AIDS therapy. 2nd ed. Churchill Livingstone (Elsevier Science), New York2003: 814-826 ([Chapter 59])
        • Lavigne J.E.
        • Shearer W.T.
        • Thompson B.
        • et al.
        • The CHAART Study Group
        Cardiovascular outcomes of pediatric seroreverters perinatally exposed to HAART: design of a longitudinal clinical study.
        Cardiovasc Toxicol. 2004; 4: 187-198
        • Zareba K.M.
        • Lavigne J.E.
        • Lipshultz S.E.
        Cardiovascular effects of HAART in infants and children of HIV-infected mothers.
        Cardiovasc Toxicol. 2004; 4: 271-280
        • Vittecoq D.
        • Escaut L.
        • Chironi G.
        • et al.
        Coronary heart disease in HIV-infected patients in the highly active antiretroviral treatment era.
        AIDS. 2003; 17: S70-S76
        • Friis-Møller N.
        • Sabin C.A.
        • Weber R.
        • et al.
        Combination antiretroviral therapy and the risk of myocardial infarction.
        N Engl J Med. 2003; 349: 1993-2003
        • Klein D.
        • Hurley L.B.
        • Quesenberry Jr., C.P.
        • 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
        • Currier J.S.
        • Taylor A.
        • Boyd F.
        • et al.
        Coronary heart disease in HIV-infected individuals.
        J Acquir Immune Defic Syndr. 2003; 33: 506-512
        • Lipshultz S.E.
        • Fisher S.D.
        • Lai W.W.
        • Miller T.L.
        Cardiac risk factors, monitoring and therapy for HIV-infected patients.
        AIDS. 2003; 17: S96-S122
        • Nanavati K.A.
        • Fisher S.D.
        • Miller T.L.
        • Lipshultz S.E.
        HIV-related cardiovascular disease and drug interactions.
        Am J Cardiovasc Drugs. 2004; 4: 315-324
        • Zareba K.M.
        • Lipshultz S.E.
        Cardiovascular complications in patients with HIV infection.
        Curr Infect Dis Rep. 2003; 5: 513-520
        • Zareba K.M.
        • Miller T.L.
        • Lipshultz Se
        Cardiovascular disease and toxicities related to HIV infection and its therapies.
        Expert Opin Drug Saf. 2005; 4: 1017-1025
        • Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
        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
        • Libby P.
        Inflammation in atherosclerosis.
        Nature. 2002; 420: 868-874
        • Fisher S.D.
        • Bowles N.E.
        • Towbin J.A.
        • Lipshultz S.E.
        Mediators in HIV-associated cardiovascular disease: a focus on cytokines and genes.
        AIDS. 2003; 17: S29-S35
        • Calara F.
        • Dimayuga P.
        • Niemann A.
        • et al.
        An animal model to study local oxidation of LDL and its biological effects in the arterial wall.
        Arterioscler Thromb Vasc Biol. 1998; 18: 884-893
        • Dichtl W.
        • Nilsson L.
        • Goncalves I.
        • et al.
        Very low-density lipoprotein activates nuclear factor-κB in endothelial cells.
        Circ Res. 1999; 84: 1085-1094
        • Wilson S.H.
        • Caplice N.M.
        • Simari R.D.
        • et al.
        Activated nuclear factor-κB is present in the coronary vasculature in experimental hypercholesterolemia.
        Atherosclerosis. 2000; 148: 23-30
        • Collins T.
        • Cybulsky M.I.
        NF-κB: pivotal mediator or innocent bystander in atherogenesis?.
        J Clin Invest. 2001; 107: 255-264
        • Li H.
        • Cybulsky M.I.
        • Gimbrone Jr., M.A.
        • Libby P.
        An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium.
        Arterioscler Thromb. 1993; 13: 197-204
        • Rosenfeld M.E.
        • Yla-Herttuala S.
        • Lipton B.A.
        • et al.
        Macrophage colony-stimulating factor mRNA and protein in atherosclerotic lesions of rabbits and humans.
        Am J Pathol. 1992; 140: 291-300
        • Clinton S.K.
        • Underwood R.
        • Hayes L.
        • et al.
        Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis.
        Am J Pathol. 1992; 140: 301-316
        • Mann J.
        • Davies M.J.
        Mechanisms of progression in native coronary artery disease: role of healed plaque disruption.
        Heart. 1999; 82: 265-268
        • Amento E.P.
        • Ehsani N.
        • Palmer H.
        • Libby P.
        Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells.
        Arterioscler Thromb. 1991; 11: 1223-1230
        • Falk E.
        Why do plaques rupture?.
        Circulation. 1992; 86: 30-42
        • Galis Z.S.
        • Sukhova G.K.
        • Lark M.W.
        • Libby P.
        Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.
        J Clin Invest. 1994; 94: 2493-2503
        • Sukhova G.K.
        • Schönbeck U.
        • Rabkin E.
        • et al.
        Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques.
        Circulation. 1999; 99: 2503-2509
        • Herman M.P.
        • Sukhova G.K.
        • Libby P.
        • et al.
        Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by transcriptional profiling.
        Circulation. 2001; 104: 1899-1904
        • de Larrañaga G.F.
        • Petroni A.
        • Deluchi G.
        • Alonso B.S.
        • Benetucci J.A.
        Viral load and disease progression as responsible for endothelial activation and/or injury in human immunodeficiency virus-1-infected patients.
        Blood Coagul Fibrinolysis. 2003; 14: 15-18
        • Wolf K.
        • Tsakiris D.A.
        • Weber R.
        • Erb P.
        • Battegay M.
        Antiretroviral therapy reduces markers of endothelial and coagulation activation in patients infected with human immunodeficiency virus type 1.
        J Infect Dis. 2002; 185: 456-462
        • Buonaguro L.
        • Barillari G.
        • Chang H.K.
        • et al.
        Effects of the human immunodeficiency virus type 1 tat protein on the expression of inflammatory cytokines.
        J Virol. 1992; 66: 7159-7167
        • Scala G.
        • Ruocco M.R.
        • Ambrosino C.
        • et al.
        The expression of the interleukin 6 gene is induced by the human immunodeficiency virus 1 TAT protein.
        J Exp Med. 1994; 179: 961-971
        • Westendorp M.O.
        • Shatrov V.A.
        • Schulze-Osthoff K.
        • et al.
        HIV-1 tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state.
        EMBO J. 1995; 14: 546-554
        • Dhawan S.
        • Puri R.K.
        • Kumar A.
        • et al.
        Human immunodeficiency virus-1-tat protein induces the cell surface expression of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in human endothelial cells.
        Blood. 1997; 90: 1535-1544
        • Dhawan S.
        • Weeks B.S.
        • Soderland C.
        • et al.
        HIV-1 infection alters monocyte interactions with human microvascular endothelial cells.
        J Immunol. 1995; 154: 422-432
        • Lafrenie R.M.
        • Wahl L.M.
        • Epstein J.S.
        • et al.
        HIV-1-Tat modulates the function of monocytes and alters their interactions with microvessel endothelial cells: a mechanism of HIV pathogenesis.
        J Immunol. 1996; 156: 1638-1645
        • Lafrenie R.M.
        • Wahl L.M.
        • Epstein J.S.
        • et al.
        HIV-1-tat protein promotes chemotaxis and invasive behavior by monocytes.
        J Immunol. 1996; 157: 974-977
        • Swingler S.
        • Mann A.
        • Jacque J.
        • et al.
        HIV Nef mediates lymphocyte chemotaxis and activation by infected macrophages.
        Nat Med. 1999; 5: 997-1003
        • Olivetta E.
        • Percario Z.
        • Fiorucci G.
        • et al.
        HIV-1 Nef induces the release of inflammatory factors from human monocyte/macrophages: involvement of Nef endocytotic signals and NF-κB.
        J Immunol. 2003; 170: 1716-1727
        • Starc T.J.
        • Lipshultz S.E.
        • Easley K.A.
        • et al.
        Incidence of cardiac abnormalities in children with human immunodeficiency virus infection: the prospective P2C2 HIV study.
        J Pediatr. 2002; 141: 327-334
        • Al-Attar I.
        • Orav E.J.
        • Exil V.
        • Vlach S.A.
        • Lipshultz S.E.
        Predictors of cardiac morbidity and related mortality in children with acquired immunodeficiency syndrome.
        J Am Coll Cardiol. 2003; 41: 1598-1605
        • Matetzky S.
        • Domingo M.
        • Kar S.
        • et al.
        Acute myocardial infarction in human immunodeficiency virus-infected patients.
        Arch Intern Med. 2003; 163: 457-460
      1. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Version November 10, 2003. Accessed 12/5/03 at

        • Périard D.
        • Telenti A.
        • Sudre P.
        • et al.
        Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors.
        Circulation. 1999; 100: 700-705
        • Walli R.
        • Herfort O.
        • Michl G.M.
        • et al.
        Treatment with protease inhibitors associated with peripheral insulin resistance and impaired glucose tolerance in HIV-1-infected patients.
        AIDS. 1998; 12: F167-F173
        • Stenina O.I.
        Regulation of vascular genes by glucose.
        Curr Pharm Des. 2005; 11: 2367-2381
        • Mulligan K.
        • Grunfeld C.
        • Tai V.W.
        • et al.
        Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection.
        J Acquir Immune Defic Syndr. 2000; 23: 35-43
        • Noor M.A.
        • Seneviratne T.
        • Aweeka F.T.
        • et al.
        Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study.
        AIDS. 2002; 16: F1-F8
        • Grinspoon S.K.
        Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus.
        Am J Med. 2005; 118: 23S-28S
        • 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: F63-F70
        • Tsiodras S.
        • Mantzoros C.
        • Hammer S.
        • Samore M.
        Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy: a 5-year cohort study.
        Arch Intern Med. 2000; 160: 2050-2056
        • Riddler S.A.
        • Smit E.
        • Cole S.R.
        • et al.
        Impact of HIV infection and HAART on serum lipids in men.
        JAMA. 2003; 289: 2978-2982
        • Grinspoon S.
        • Carr A.
        Cardiovascular risk and body-fat abnormalities in HIV-infected adults.
        N Engl J Med. 2005; 352: 48-62
        • Hatano H.
        • Miller K.D.
        • Yoder C.P.
        • et al.
        Metabolic and anthropometric consequences of interruption of highly active antiretroviral therapy.
        AIDS. 2000; 14: 1935-1942
        • Law M.
        • Friis-Møller N.
        • Weber R.
        • et al.
        Modeling the 3-year risk of myocardial infarction among participants in the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study.
        HIV Med. 2003; 4: 1-10
        • 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 Res. 2000; 5: 329-333
        • Holmberg S.D.
        • Moorman A.C.
        • Williamson J.M.
        • et al.
        Protease inhibitors and cardiovascular outcomes in patients with HIV-1.
        Lancet. 2002; 360: 1747-1748
        • Mary-Krause M.
        • Cotte L.
        • Simon A.
        • Partisani M.
        • Costagliola D.
        • The Clinical Epidemiology Group from the French Hospital Database
        Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men.
        AIDS. 2003; 17: 2479-2486
        • Escaut L.
        • Monsuez J.J.
        • Chironi G.
        • et al.
        Coronary artery disease in HIV-infected patients.
        Intensive Care Med. 2003; 29: 969-973
        • Coplan P.M.
        • Nikas A.
        • Japour A.
        • et al.
        Incidence of myocardial infarction in randomized clinical trials of protease inhibitor-based antiretroviral therapy: an analysis of four different protease inhibitors.
        AIDS Res Hum Retroviruses. 2003; 19: 449-455
        • Bozzette S.A.
        • Ake C.F.
        • Tam H.K.
        • Chang S.W.
        • Louis T.A.
        Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection.
        N Engl J Med. 2003; 348: 702-710
        • Martinez E.
        • Garcia-Viejo M.A.
        • Blanco J.L.
        • et al.
        Impact of switching from human immunodeficiency virus type 1 protease inhibitors to efavirenz in successfully treated adults with lipodystrophy.
        Clin Infect Dis. 2000; 31: 1266-1273
        • Raffi F.
        • Reliquet V.
        • Podzamczer D.
        • Pollard R.B.
        Efficacy of nevirapine-based HAART in HIV-1-infected, treatment-naive persons with high and low baseline viral loads.
        HIV Clin Trials. 2001; 2: 317-322
        • Ruiz L.
        • Negredo E.
        • Domingo P.
        • et al.
        Antiretroviral treatment simplification with nevirapine in protease-inhibitor experienced patients with HIV-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study.
        J Acquir Immune Defic Syndr. 2001; 27: 229-236
        • Van Leth F.
        • Phanuphak P.
        • Ruxrungtham K.
        • et al.
        Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomized open-label trial, the 2NN study.
        Lancet. 2004; 363: 1253-1256
        • Clevenbergh P.
        • Garraffo R.
        • Dellamonica P.
        Impact of various antiretroviral drugs and their plasma concentrations on plasma lipids in heavily pretreated HIV-infected patients.
        HIV Clin Trials. 2003; 4: 330-336
        • Estrada V.
        • De Villar N.G.P.
        • Larrad M.T.M.
        • et al.
        Long-term metabolic consequences of switching from protease inhibitors to efavirenz in therapy for human immunodeficiency virus-infected patients with lipoatrophy.
        Clin Infect Dis. 2002; 35: 69-76
        • Martínez E.
        • Arnaiz J.A.
        • Podzamczer D.
        • et al.
        Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection.
        N Engl J Med. 2003; 349: 1036-1046
        • van der Valk M.
        • Kastelein J.
        • Murphy R.
        • et al.
        Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile.
        AIDS. 2001; 15: 2407-2414
        • Tebas P.
        • Yarasheski K.
        • Powderly W.G.
        • et al.
        A prospective open label pilot trial of a maintenance nevirapine (NVP)-containing regimen in patients with undetectable viral loads (VL) on protease inhibitor (PI) regimens for at least 6 months.
        AIDS Res Hum Retroviruses. 2003; 19: 449-455
        • 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
        • Negredo E.
        • Cruz L.
        • Paredes R.
        • et al.
        Virological, immunological, and clinical impact of switching from protease inhibitors to nevirapine or to efavirenz in patients with human immunodeficiency virus infection and long-lasting viral suppression.
        Clin Infect Dis. 2002; 34: 504-510
        • Schambelan M.
        • Benson C.A.
        • Carr A.
        • et al.
        Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: recommendations of an International AIDS Society-USA panel.
        J Acquir Immune Defic Syndr. 2002; 31: 257-275
        • Scevola D.
        • Di Matteo A.
        • Lanzarini P.
        • et al.
        Effects of exercise and strength training on cardiovascular status in HIV-infected patients receiving highly active antiretroviral therapy.
        AIDS. 2003; 17: S123-S129
        • Orrick J.J.
        • Sateinart C.R.
        • Atazanavir
        Ann Pharmacolother. 2004; 38: 1664-1674
        • Hoffmann C.
        • Jaeger H.
        Cardiology and AIDS—HAART and the consequences.
        Ann NY Acad Sci. 2001; 946: 130-144
        • Erikssen G.
        • Liestol K.
        • Bjornholt J.
        • et al.
        Changes in physical fitness and changes in mortality.
        Lancet. 1998; 352: 759-762
        • Shephard R.J.
        Exercise, immune function and HIV infection.
        J Sports Med Phys Fitness. 1998; 38: 101-110
        • Shepard R.J.
        • Shek P.N.
        Impact of physical activity and sport on the immune system.
        Rev Environ Health. 1996; 11: 133-147
        • Cannon J.G.
        • Fielding R.A.
        • Fiatarone M.A.
        • et al.
        Increased interleukin 1 beta in human skeletal muscle after exercise.
        Am J Physiol. 1989; 257: R451-R455
        • Boas S.R.
        • Joswiak M.L.
        • Nixon P.A.
        • et al.
        Effects of anaerobic exercise on the immune system in eight- to seventeen-year-old trained and untrained boys.
        J Pediatr. 1996; 129: 846-855
        • Nieman D.C.
        Immune response to heavy exertion.
        J Appl Physiol. 1997; 82: 1385-1394
        • Rigsby L.W.
        • Dishman R.K.
        • Jackson A.W.
        • Maclean G.S.
        • Raven P.B.
        Effects of exercise training on men seropositive for the human immunodeficiency virus-1.
        Med Sci Sports Exerc. 1992; 24: 6-12
        • LaPierre A.
        Aerobic exercise training in an AIDS risk group.
        Int J Sports Med. 1991; 12: S53-S57
        • Mustafa T.
        • Sy F.S.
        • Macera C.A.
        • et al.
        Association between exercise and HIV disease progression in a cohort of homosexual men.
        Ann Epidemiol. 1999; 9: 127-131
        • Spence D.W.
        • Galantino M.L.
        • Mossberg K.A.
        • Zimmerman S.O.
        Progressive resistance exercise: effect on muscle function and anthropometry of a select AIDS population.
        Arch Phys Med Rehabil. 1990; 71: 644-648
        • Roubenoff R.
        • McDermott A.
        • Wood M.
        • Suri J.
        Feasibility of increasing lean body mass in HIV-infected adults using progressive resistance training.
        Med Sci Sports Exerc. 1998; 30: S183
        • Roubenoff R.
        • Weiss L.
        • McDermott A.
        • et al.
        A pilot study of exercise training to reduce trunk fat in adults with HIV-associated fat redistribution.
        AIDS. 1999; 13: 1373-1375
        • Jones S.P.
        • Doran D.A.
        • Leatt P.B.
        • Maher B.
        • Pirmohamed M.
        Short-term exercise training improves body composition and hyperlipidaemia in HIV-positive individuals with lipodystrophy.
        AIDS. 2001; 15: 2049-2051
        • Driscoll S.D.
        • Meininger G.E.
        • Lareau M.T.
        • et al.
        Effects of exercise training and metformin on body composition and cardiovascular indices in HIV-infected patients.
        AIDS. 2004; 18: 465-473
        • Yang A.L.
        • Chen H.I.
        Chronic exercise reduces adhesion molecules/iNOS expression and partially reverses vascular responsiveness in hypercholesterolemic rabbit aortae.
        Atherosclerosis. 2003; 169: 11-17
        • Yang A.L.
        • Jen C.J.
        • Chen H.A.
        Effects of high-cholesterol diet and parallel exercise training on the vascular function of rabbit aortas: a time course study.
        J Appl Physiol. 2003; 95: 1194-1200
        • Arosio E.
        • Minuz P.
        • Prior M.
        • et al.
        Vascular adhesion molecule-1 and markers of platelet function before and after a treatment with iloprost or a supervised physical exercise program in patients with peripheral arterial disease.
        Life Sci. 2001; 69: 421-433
        • Stringer W.W.
        Mechanisms of exercise limitation in HIV+ individuals.
        Med Sci Sports Exerc. 2000; 32: S412-S421
        • Miller T.L.
        • Horgan S.
        • Lipshultz S.E.
        Exercise rehabilitation of pediatric patients with cardiovascular disease.
        Prog Pediatr Cardiol. 2005; 20: 27-37
        • Stein J.H.
        • Klein M.A.
        • Bellehumeur J.L.
        • et al.
        Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction.
        Circulation. 2001; 104: 257-262
        • Dube M.P.
        • Stein J.H.
        • Fichtenbaum C.J.
        • et al.
        Guidelines for the evaluation and management of dylipidemia in human immunodeficiency virus (HIV)-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: 613-627
        • Dube M.P.
        • Sprecher D.
        • Henry W.K.
        • et al.
        Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group.
        Clin Infect Dis. 2000; 31: 1216-1224
        • Benesic A.
        • Zilly M.
        • Kluge F.
        • et al.
        Lipid lowering therapy with fluvastatin and pravastatin in patients with HIV infection and antiretroviral therapy: comparison of efficacy and interaction with indinavir.
        Infection. 2004; 32: 229-233
        • Moyle G.J.
        • Lloyd M.
        • Reynolds B.
        • et al.
        Dietary advice with or without pravastatin for the management of hypercholesterolemia associated with protease inhibitor therapy.
        AIDS. 2001; 15: 1503-1508
        • Stein J.H.
        • Merwood M.A.
        • Bellehumeur J.L.
        • et al.
        Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors.
        Am Heart J. 2004; 147: 713-724
        • Badiou S.
        • De Boever C.M.
        • Dupuy A.M.
        • et al.
        Fenofibrate improves the atherogenic lipid profile and enhances LDL resistance to oxidation in HIV-positive adults.
        Atherosclerosis. 2004; 172: 273-279
        • Kalinowski L.
        • Dobrucki L.W.
        • Brovkovych V.
        • Malinski T.
        Increased nitric oxide bioavailability in endothelial cells contributes to the pleiotropic effect of cerivastatin.
        Circulation. 2002; 105: 933-938
        • Kalinowski L.
        • Dobrucki I.T.
        • Malinski T.
        Cerivastatin potentiates nitric oxide release and enos expression through inhibition of isoprenoids synthesis.
        J Physiol Pharmacol. 2002; 53: 585-595
        • Suzumura K.
        • Yasuhara M.
        • Tanaka K.
        • et al.
        An in vitro study of the hydroxyl radical scavenging property of fluvastatin, and HMG-CoA reductase inhibitor.
        Chem Pharm Bull. 1999; 47: 1010-1012
        • Tsiara S.
        • Elisaf M.
        • Mikhailidis D.P.
        Early vascular benefits of statin therapy.
        Curr Med Res Opin. 2003; 19: 540-556