Human immunodeficiency virus and highly active antiretroviral therapy-associated metabolic disorders and risk factors for cardiovascular disease

Metabolic Syndrome and Related Disorders

Volumn 7, Issue 5, 2009, Pages 401-410

  Anuurad, Erdembileg ^a   Semrad, Alison ^a   Berglund, Lars ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b VA NORTHERN CALIFORNIA HEALTH CARE SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INDINAVIR; LOPINAVIR; NELFINAVIR; NEVIRAPINE; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; STAVUDINE; TENOFOVIR;

CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; DYSLIPIDEMIA; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INSULIN RESISTANCE; LIPODYSTROPHY; METABOLIC DISORDER; OBESITY; OSTEOPOROSIS; PRIORITY JOURNAL; REVIEW;

ANTI-RETROVIRAL AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; BONE DENSITY; BONE REMODELING; CARDIOVASCULAR DISEASES; ENDOCRINE SYSTEM DISEASES; HIV INFECTIONS; HIV-ASSOCIATED LIPODYSTROPHY SYNDROME; HUMANS; LIPID METABOLISM; METABOLIC DISEASES; METABOLIC SYNDROME X; RISK ASSESSMENT; RISK FACTORS;

EID: 70350334825     PISSN: 15404196     EISSN: None     Source Type: Journal    
DOI: 10.1089/met.2009.0705.diss     Document Type: Review

References (122)

1. Pneumocystis pneumonia-Los Angeles. MMWR 1981;30: 250-252.
2. UNAIDS, WHO. AIDS epidemic update: December 2007. Geneva: Joint UN Programme on HIV/AIDS, World Health Organization; 2007.
3. Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR, Sax PE, Weinstein MC, Freedberg KA. The survival benefi ts of AIDS treatment in the United States. J Infect Dis 2006;194:11-19.
4. Friis-Moller N, Sabin CA, Weber R, d'Arminio Monforte A, El-Sadr WM, Reiss P, Thiebaut R, Morfeldt L, De Wit S, Pradier C, Calvo G, Law MG, Kirk O, Phillips AN, Lundgren JD. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003;349:1993-2003.
5. Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005;352:48-62. (Pubitemid 40075680)
6. Lohse N, Hansen AB, Pedersen G, Kronborg G, Gerstoft J, Sorensen HT, Vaeth M, Obel N. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med 2007;146:87-95.
7. Penzak SR, Chuck SK. Hyperlipidemia associated with HIV protease inhibitor use: Pathophysiology, prevalence, risk factors and treatment. Scand J Infect Dis 2000;32:111-123.
8. Constans J, Pellegrin JL, Peuchant E, Dumon MF, Pellegrin I, Sergeant C, Simonoff M, Brossard G, Barbeau P, Fleury H, et al. Plasma lipids in HIV-infected patients: A prospective study in 95 patients. Eur J Clin Invest 1994;24:416-420.
9. Asztalos BF, Schaefer EJ, Horvath KV, Cox CE, Skinner S, Gerrior J, Gorbach SL, Wanke C. Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients. Atherosclerosis 2006;184:72-77.
10. Rose H, Woolley I, Hoy J, Dart A, Bryant B, Mijch A, Sviridov D. HIV infection and high-density lipoprotein: The effect of the disease vs the effect of treatment. Metabolism 2006;55:90-95.
11. Zangerle R, Sarcletti M, Gallati H, Reibnegger G, Wachter H, Fuchs D. Decreased plasma concentrations of HDL cholesterol in HIV-infected individuals are associated with immune activation. J Acq Immune Defi c Syndr 1994;7:1149-1156.
12. Meininger G, Hadigan C, Laposata M, Brown J, Rabe J, Louca J, Aliabadi N, Grinspoon S. Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodefi ciency virus-infected subjects with fat redistribution. Metabolism 2002;51:260-266.
13. Sekhar RV, Jahoor F, White AC, Pownall HJ, Visnegarwala F, Rodriguez-Barradas MC, Sharma M, Reeds PJ, Balasubramanyam A. Metabolic basis of HIV-lipodystrophy syndrome. Am J Physiol Endocrinol Metab 2002;283:E332-E337.
14. Reeds DN, Yarasheski KE, Fontana L, Cade WT, Laciny E, DeMoss A, Patterson BW, Powderly WG, Klein S. Alterations in liver, muscle, and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia. Am J Physiol Endocrinol Metab 2006;290:E47-E53.
15. Mujawar Z, Rose H, Morrow MP, Pushkarsky T, Dubrovsky L, Mukhamedova N, Fu Y, Dart A, Orenstein JM, Bobryshev YV, Bukrinsky M, Sviridov D. Human immunodefi ciency virus impairs reverse cholesterol transport from macrophages. PLoS Biol 2006;4:e365.
16. Haugaard SB, Andersen O, Pedersen SB, Dela F, Fenger M, Richelsen B, Madsbad S, Iversen J. Tumor necrosis factor alpha is associated with insulin-mediated suppression of free fatty acids and net lipid oxidation in HIV-infected patients with lipodystrophy. Metabolism 2006;55:175-182.
17. El-Sadr WM, Mullin CM, Carr A, Gibert C, Rappoport C, Visnegarwala F, Grunfeld C, Raghavan SS. Effects of HIV disease on lipid, glucose and insulin levels: Results from a large antiretroviral-naive cohort. HIV Med 2005;6:114-121.
18. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, Cooper DA. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS (London, England) 1998;12:F51-F58.
19. Capaldini L. Protease inhibitors' metabolic side effects: Cholesterol, triglycerides, blood sugar, and "Crix belly." Interview with Lisa Capaldini, M.D. Interview by John S. James. AIDS Treat News 1997:1-4.
20. Kino T, Mirani M, Alesci S, Chrousos GP. AIDS-related lipodystrophy/ insulin resistance syndrome. Horm Metab Res 2003;35:129-136.
21. Barbaro G. Metabolic and cardiovascular complications of highly active antiretroviral therapy for HIV infection. Curr HIV Res 2006;4:79-85.
22. Reeds DN, Mittendorfer B, Patterson BW, Powderly WG, Yarasheski KE, Klein S. Alterations in lipid kinetics in men with HIV-dyslipidemia. Am J Physiol Endocrinol Metab 2003;285:E490-E497.
23. Schmitz M, Michl GM, Walli R, Bogner J, Bedynek A, Seidel D, Goebel FD, Demant T. Alterations of apolipoprotein B metabolism in HIV-infected patients with antiretroviral combination therapy. J Acq Immune Defi c Syndr 2001;26:225-235.
24. Shahmanesh M, Das S, Stolinski M, Shojaee-Moradie F, Jackson NC, Jefferson W, Cramb R, Nightingale P, Umpleby AM. Antiretroviral treatment reduces very-low-density lipoprotein and intermediate-density lipoprotein apolipoprotein B fractional catabolic rate in human immunodefi ciency virusinfected patients with mild dyslipidemia. J Clin Endocrinol Metab 2005;90:755-760.
25. Baril L, Beucler I, Valantin MA, Bruckert E, Bonnefont-Rousselot D, Coutellier A, Caumes E, Katlama C, Bricaire F. Low lipolytic enzyme activity in patients with severe hypertriglyceridemia on highly active antiretroviral therapy. AIDS (London, England) 2001;15:415-417.
26. Periard D, Telenti A, Sudre P, Cheseaux JJ, Halfon P, Reymond MJ, Marcovina SM, Glauser MP, Nicod P, Darioli R, Mooser V. Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. The Swiss HIV Cohort Study. Circulation 1999;100:700-705.
27. Anuurad E, Thomas-Geevarghese A, Devaraj S, Albu J, Minolfo R, El-Sadr WM, Lu G, Karmally W, Berglund L. Increased lipoprotein remnant cholesterol levels in HIV-positive patients during antiretroviral therapy. Atherosclerosis 2008;198:192-197.
28. Shikuma CM, Yang Y, Glesby MJ, Meyer WA, 3rd, Tashima KT, Ribaudo HJ, Webb N, Bastow B, Kuritzkes DR, Gulick RM. Metabolic effects of protease inhibitor-sparing antiretroviral regimens given as initial treatment of HIV-1 Infection (AIDS Clinical Trials Group Study A5095). J Acq Immune Defi c Syndr 2007;44:540-550.
29. Friis-Moller N, Weber R, Reiss P, Thiebaut R, Kirk O, d'Arminio Monforte A, Pradier C, Morfeldt L, Mateu S, Law M, El-Sadr W, De Wit S, Sabin CA, Phillips AN, Lundgren JD. Cardiovascular disease risk factors in HIV patients-association with antiretroviral therapy. Results from the DAD study. AIDS (London, England) 2003;17:1179-1193.
30. Llibre JM, Domingo P, Palacios R, Santos J, Perez-Elias MJ, Sanchez-de la Rosa R, Miralles C, Antela A, Moreno S. Sustained improvement of dyslipidaemia in HAART-treated patients replacing stavudine with tenofovir. AIDS (London, England) 2006;20:1407-1414.
31. John M, Moore CB, James IR, Nolan D, Upton RP, McKinnon EJ, Mallal SA. Chronic hyperlactatemia in HIV-infected patients taking antiretroviral therapy. AIDS (London, England) 2001;15:717-723.
32. Brinkman K, Smeitink JA, Romijn JA, Reiss P. Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviraltherapy- related lipodystrophy. Lancet 1999;354:1112-1115.
33. Kakuda TN, Brundage RC, Anderson PL, Fletcher CV. Nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity as an etiology for lipodystrophy. AIDS (London, England) 1999;13:2311-2312.
34. Fontas E, van Leth F, Sabin CA, Friis-Moller N, Rickenbach M, d'Arminio Monforte A, Kirk O, Dupon M, Morfeldt L, Mateu S, Petoumenos K, El-Sadr W, de Wit S, Lundgren JD, Pradier C, Reiss P. Lipid profi les in HIV-infected patients receiving combination antiretroviral therapy: Are different antiretroviral drugs associated with different lipid profi les? J Infect Dis 2004;189:1056-1074.
35. Dube MP, Stein JH, Aberg JA, Fichtenbaum CJ, Gerber JG, Tashima KT, Henry WK, Currier JS, Sprecher D, Glesby MJ. Guidelines for the evaluation and management of dyslipidemia in human immunodefi ciency 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.
36. van Leth F, Phanuphak P, Stroes E, Gazzard B, Cahn P, Raffi F, Wood R, Bloch M, Katlama C, Kastelein JJ, Schechter M, Murphy RL, Horban A, Hall DB, Lange JM, Reiss P. Nevirapine and efavirenz elicit different changes in lipid profi les in antiretroviral- therapy-naive patients infected with HIV-1. PLoS Med 2004;1:e19.
37. Shor-Posner G, Basit A, Lu Y, Cabrejos C, Chang J, Fletcher M, Mantero-Atienza E, Baum MK. Hypocholesterolemia is associated with immune dysfunction in early human immunodefi - ciency virus-1 infection. Am J Med 1993;94:515-519.
38. Samaras K, Wand H, Law M, Emery S, Cooper D, Carr A. Prevalence of metabolic syndrome in HIV-infected patients receiving highly active antiretroviral therapy using International Diabetes Foundation and Adult Treatment Panel III criteria: Associations with insulin resistance, disturbed body fat compartmentalization, elevated C-reactive protein, and [corrected] hypoadiponectinemia. Diabetes Care 2007;30:113-119. (Pubitemid 46052508)
39. Jacobson DL, Tang AM, Spiegelman D, Thomas AM, Skinner S, Gorbach SL, Wanke C. 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 Acq Immune Defi c Syndr 2006;43:458-466.
40. Wand H, Calmy A, Carey DL, Samaras K, Carr A, Law MG, Cooper DA, Emery S. Metabolic syndrome, cardiovascular disease and type 2 diabetes mellitus after initiation of antiretroviral therapy in HIV infection. AIDS (London, England) 2007;21:2445-2453.
41. Carr A. HIV lipodystrophy: Risk factors, pathogenesis, diagnosis and management. AIDS (London, England) 2003;17(Suppl 1):S141-S148.
42. Fisher SD, Miller TL, Lipshultz SE. Impact of HIV and highly active antiretroviral therapy on leukocyte adhesion molecules, arterial infl ammation, dyslipidemia, and atherosclerosis. Atherosclerosis 2006;185:1-11.
43. Guardiola M, Ferre R, Salazar J, Alonso-Villaverde C, Coll B, Parra S, Masana L, Ribalta J. Protease inhibitor-associated dyslipidemia in HIV-infected patients is strongly infl uenced by the APOA5-1131TšC gene variation. Clin Chem 2006;52: 1914-1919.
44. Berthold HK, Parhofer KG, Ritter MM, Addo M, Wasmuth JC, Schliefer K, Spengler U, Rockstroh JK. Infl uence of protease inhibitor therapy on lipoprotein metabolism. J Intern Med 1999;246:567-575.
45. Fessel WJ, Follansbee SE, Rego J. High-density lipoprotein cholesterol is low in HIV-infected patients with lipodystrophic fat expansions: Implications for pathogenesis of fat redistribution. AIDS (London, England) 2002;16:1785-1789.
46. Pernerstorfer-Schoen H, Jilma B, Perschler A, Wichlas S, Schindler K, Schindl A, Rieger A, Wagner OF, Quehenberger P. Sex differences in HAART-associated dyslipidaemia. AIDS (London, England) 2001;15:725-734.
47. Riddler SA, Smit E, Cole SR, Li R, Chmiel JS, Dobs A, Palella F, Visscher B, Evans R, Kingsley LA. Impact of HIV infection and HAART on serum lipids in men. JAMA 2003;289:2978-2982.
48. Feingold KR, Krauss RM, Pang M, Doerrler W, Jensen P, Grunfeld C. The hypertriglyceridemia of acquired immunode- fi ciency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B. J Clin Endocrinol Metab 1993;76:1423-1427.
49. Constans J, Pellegrin JL, Peuchant E, Dumon MF, Simonoff M, Clerc M, Leng B, Conri C. High plasma lipoprotein (a) in HIVpositive patients. Lancet 1993;341:1099-1100.
50. Kritz H, Efthimiou Y, Stamatopoulos J, Najemnik C, Sinzinger H. Association of lipoprotein(a), prostaglandin I(2)- synthesis stimulating plasma factor, biological half-life of prostaglandin I(2)and high-density lipoproteins in HIV-1 infection of different stages. Prostaglandins, Leukot Essent Fatty Acids 2000; 63:309-314.
51. Rimland D, Guest JL, Hernandez-Ramos I, Del Rio C, Le NA, Brown WV. Antiretroviral therapy in HIV-positive women is associated with increased apolipoproteins and total cholesterol. J Acq Immune Defi c Syndr 2006;42:307-313.
52. Bard JM, Lassalle R, Capeau J, Bach-Ngohou K, Nazih- Sanderson F, Remy G, Reynes J, Ecobichon JL, Saves M, Raffi F. Association of apolipoproteins C3 and E with metabolic changes in HIV-infected adults treated with a proteaseinhibitor- containing antiretroviral therapy. Antivir Ther 2006;11:361-370.
53. Bonnet F, Balestre E, Thiebaut R, Mercie P, Dupon M, Morlat P, Dabis F. Fibrates or statins and lipid plasma levels in 245 patients treated with highly active antiretroviral therapy. Aquitaine Cohort, France, 1999-2001. HIV Med 2004;5:133-139.
54. Grunfeld C, Doerrler W, Pang M, Jensen P, Weisgraber KH, Feingold KR. Abnormalities of apolipoprotein E in the acquired immunodefi ciency syndrome. J Clin Endocrinol Metab 1997;82:3734-3740.
55. Stefas E, Rucheton M, Graafl and H, Moynier M, Sompeyrac C, Bahraoui EM, Veas F. Human plasmatic apolipoprotein H binds human immunodefi ciency virus type 1 and type 2 proteins. AIDS Res Hum Retrovir 1997;13:97-104.
56. Carpentier A, Patterson BW, Uffelman KD, Salit I, Lewis GF. Mechanism of highly active anti-retroviral therapy-induced hyperlipidemia in HIV-infected individuals. Atherosclerosis 2005;178:165-172.
57. Petit JM, Duong M, Florentin E, Duvillard L, Chavanet P, Brun JM, Portier H, Gambert P, Verges B. Increased VLDL-apoB and IDL-apoB production rates in nonlipodystrophic HIV-infected patients on a protease inhibitor-containing regimen: A stable isotope kinetic study. J Lipid Res 2003;44:1692-1697.
58. Purnell JQ, Zambon A, Knopp RH, Pizzuti DJ, Achari R, Leonard JM, Locke C, Brunzell JD. Effect of ritonavir on lipids and post-heparin lipase activities in normal subjects. AIDS (London, England) 2000;14:51-57.
59. Sekhar RV, Jahoor F, Pownall HJ, Rehman K, Gaubatz J, Iyer D, Balasubramanyam A. Severely dysregulated disposal of postprandial triacylglycerols exacerbates hypertriacylglycerolemia in HIV lipodystrophy syndrome. Am J Clin Nutr 2005;81:1405-1410.
60. van Wijk JP, Cabezas MC, de Koning EJ, Rabelink TJ, van der Geest R, Hoepelman IM. In vivo evidence of impaired peripheral fatty acid trapping in patients with human immunodefi - ciency virus-associated lipodystrophy. J Clin Endocrinol Metab 2005;90:3575-3582.
61. Miserez AR, Muller PY, Spaniol V. Indinavir inhibits sterolregulatory element-binding protein-1c-dependent lipoprotein lipase and fatty acid synthase gene activations. AIDS (London, England) 2002;16:1587-1594.
62. Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1998;351:1881-1883. (Pubitemid 28279721)
63. Hu C, Oliver JA, Goldberg MR, Al-Awqati Q. LRP: A new adhesion molecule for endothelial and smooth muscle cells. Am J Physiol Renal Physiol 2001;281:F739-F750.
64. Zimmermann R, Panzenbock U, Wintersperger A, Levak- Frank S, Graier W, Glatter O, Fritz G, Kostner GM, Zechner R. Lipoprotein lipase mediates the uptake of glycated LDL in fi broblasts, endothelial cells, and macrophages. Diabetes 2001;50:1643-1653.
65. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: A cohort study. Lancet 1999;353:2093-2099.
66. Fauvel J, Bonnet E, Ruidavets JB, Ferrieres J, Toffoletti A, Massip P, Chap H, Perret B. An interaction between apo C-III variants and protease inhibitors contributes to high triglyceride/ low HDL levels in treated HIV patients. AIDS (London, England) 2001;15:2397-2406.
67. Tarr PE, Taffe P, Bleiber G, Furrer H, Rotger M, Martinez R, Hirschel B, Battegay M, Weber R, Vernazza P, Bernasconi E, Darioli R, Rickenbach M, Ledergerber B, Telenti A. Modeling the infl uence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. J Infect Dis 2005;191:1419-1426.
68. Foulkes AS, Wohl DA, Frank I, Puleo E, Restine S, Wolfe ML, Dube MP, Tebas P, Reilly MP. Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy. PLoS Med 2006;3:e52.
69. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodefi ciency virus disease. J Clin Endocrinol Metab 2007;92:2506-2512.
70. Currier JS, Taylor A, Boyd F, Dezii CM, Kawabata H, Burtcel B, Maa JF, Hodder S. Coronary heart disease in HIV-infected individuals. J Acquired Immune Defi c Syndr 2003;33:506-512.
71. Bozzette SA, Ake CF, Tam HK, Chang SW, Louis TA. Cardiovascular and cerebrovascular events in patients treated for human immunodefi ciency virus infection. N Engl J Med 2003;348:702-710.
72. Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, De Wit S, Law M, D'Arminio Monforte A, Friis-Moller N, Kirk O, Pradier C, Weller I, Phillips AN, Lundgren JD. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: A multi-cohort collaboration. Lancet 2008;371:1417-1426.
73. Klein D, Hurley LB, Quesenberry CP, Jr., Sidney S. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acq Immune Defi c Syndr 2002;30:471-477.
74. Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, Thiebaut R, De Wit S, Kirk O, Fontas E, Law MG, Phillips A, Lundgren JD. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007;356:1723-1735.
75. Mary-Krause M, Cotte L, Simon A, Partisani M, Costagliola D. Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS (London, England) 2003;17:2479-2486.
76. Bonnet D, Aggoun Y, Szezepanski I, Bellal N, Blanche S. Arterial stiffness and endothelial dysfunction in HIV-infected children. AIDS (London, England) 2004;18:1037-1041.
77. Hsue PY, Lo JC, Franklin A, Bolger AF, Martin JN, Deeks SG, Waters DD. Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection. Circulation 2004;109:1603-1608.
78. Depairon M, Chessex S, Sudre P, Rodondi N, Doser N, Chave JP, Riesen W, Nicod P, Darioli R, Telenti A, Mooser V. Premature atherosclerosis in HIV-infected individuals-focus on protease inhibitor therapy. AIDS (London, England) 2001;15: 329-334.
79. Currier JS, Kendall MA, Zackin R, Henry WK, Alston-Smith B, Torriani FJ, Schouten J, Mickelberg K, Li Y, Hodis HN. Carotid artery intima-media thickness and HIV infection: Traditional risk factors overshadow impact of protease inhibitor exposure. AIDS (London, England) 2005;19:927-933.
80. Maggi P, Serio G, Epifani G, Fiorentino G, Saracino A, Fico C, Perilli F, Lillo A, Ferraro S, Gargiulo M, Chirianni A, Angarano G, Regina G, Pastore G. Premature lesions of the carotid vessels in HIV-1-infected patients treated with protease inhibitors. AIDS (London, England) 2000;14:F123-F128.
81. Coplan PM, Nikas A, Japour A, Cormier K, Maradit-Kremers H, Lewis R, Xu Y, DiNubile MJ. Incidence of myocardial infarction in randomized clinical trials of protease inhibitor-based antiretroviral therapy: An analysis of four different protease inhibitors. AIDS Res Hum Retrovir 2003;19:449-455.
82. Sellmeyer DE, Grunfeld C. Endocrine and metabolic disturbances in human immunodefi ciency virus infection and the acquired immune defi ciency syndrome. Endocr Rev 1996;17: 518-532.
83. Hofbauer LC, Heufelder AE. Endocrine implications of human immunodefi ciency virus infection. Medicine 1996;75:262-278.
84. Hoshino Y, Yamashita N, Nakamura T, Iwamoto A. Prospective examination of adrenocortical function in advanced AIDS patients. Endocr J 2002;49:641-647.
85. Merenich JA, McDermott MT, Asp AA, Harrison SM, Kidd GS. Evidence of endocrine involvement early in the course of human immunodefi ciency virus infection. J Clin Endocrinol Metab 1990;70:566-571.
86. Mayo J, Collazos J, Martinez E, Ibarra S. Adrenal function in the human immunodefi ciency virus-infected patient. Arch Intern Med 2002;162:1095-1098.
87. Madge S, Smith CJ, Lampe FC, Thomas M, Johnson MA, Youle M, Vanderpump M. No association between HIV disease and its treatment and thyroid function. HIV Med 2007;8:22-27.
88. Hoffmann CJ, Brown TT. Thyroid function abnormalities in HIV-infected patients. Clin Infect Dis 2007;45:488-494.
89. Wilson LD, Truong MP, Barber AR, Aoki TT. Anterior pitutiary and pitutiary-dependent target organ function in men infected with the human immunodefi ciency virus. Metabolism 1996;45:738-746.
90. Dobs AS, Dempsey MA, Ladenson PW, Polk BF. Endocrine disorders in men infected with human immunodefi ciency virus. Am J Med 1988;84:611-616.
91. Asboe D, Catalan J, Mandalia S, Dedes N, Florence E, Schrooten W, Noestlinger C, Colebunders R. Sexual dysfunction in HIVpositive men is multi-factorial: A study of prevalence and associated factors. AIDS Care 2007;19:955-965.
92. Wunder DM, Fux CA, Bersinger NA, Mueller NJ, Hirschel B, Cavassini M, Elzi L, Schmid P, Bernasconi E, Mueller B, Furrer H. Androgen and gonadotropin patterns differ in HIV-1- infected men who develop lipoatrophy during antiretroviral therapy: A case-control study. HIV Med 2008;9:427-432.
93. Congote LF. Monitoring insulin-like growth factors in HIV infection and AIDS. Clin Chim Acta 2005;361:30-53.
94. Zapanti E, Terzidis K, Chrousos G. Dysfunction of the hypothalamic- pituitary-adrenal axis in HIV infection and disease. Hormones (Athens, Greece) 2008;7:205-216.
95. Cole SW. Psychosocial infl uences on HIV-1 disease progression: Neural, endocrine, and virologic mechanisms. Psychosomat Med 2008;70:562-568.
96. Lo JC, Schambelan M. Reproductive function in human immunodefi ciency virus infection. J Clin Endocrinol Metab 2001;86:2338-2343.
97. Cohan GR. HIV-associated hypogonadism. The AIDS Reader 2006;16:341-345, 348, 352-1344
98. Zandman-Goddard G, Shoenfeld Y. HIV and autoimmunity. Autoimmun Rev 2002;1:329-337.
99. Bhasin S, Singh AB, Javanbakht M. Neuroendocrine abnormalities associated with HIV infection. Endocrinol Metab Clinics N Am 2001;30:749-764, viii.
100. Triant VA, Brown TT, Lee H, Grinspoon SK. Fracture prevalence among human immunodefi ciency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 2008;93:3499-3504.
101. Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Lo Y, Klein RS. Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection. AIDS 2007;21:617-623.
102. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: A meta-analytic review. AIDS (London, England) 2006;20:2165-2174.
103. Cazanave C, Dupon M, Lavignolle-Aurillac V, Barthe N, Lawson-Ayayi S, Mehsen N, Mercie P, Morlat P, Thiebaut R, Dabis F. Reduced bone mineral density in HIV-infected patients: Prevalence and associated factors. AIDS 2008;22:395-402.
104. Bruera D, Luna N, David DO, Bergoglio LM, Zamudio J. Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy. AIDS 2003;17: 1917-1923.
105. Fausto A, Bongiovanni M, Cicconi P, Menicagli L, Ligabo EV, Melzi S, Bini T, Sardanelli F, Cornalba G, Monforte A. Potential predictive factors of osteoporosis in HIV-positive subjects. Bone 2006;38:893-897.
106. Amiel C, Ostertag A, Slama L, Baudoin C, N'Guyen T, Lajeunie E, Neit-Ngeilh L, Rozenbaum W, De Vernejoul MC. BMD is reduced in HIV-infected men irrespective of treatment. J Bone Miner Res 2004;19:402-409.
107. Garcia Aparicio AM, Munoz Fernandez S, Gonzalez J, Arribas JR, Pena JM, Vazquez JJ, Martinez ME, Coya J, Martin Mola E. Abnormalities in the bone mineral metabolism in HIV-infected patients. Clin Rheumatol 2006;25:537-539.
108. Landonio S, Quirino T, Bonfanti P, Gabris A, Boccassini L, Gulisano C, Vulpio L, Ricci E, Carrabba M, Vigevani GM. Osteopenia and osteoporosis in HIV+ patients, untreated or receiving HAART. Biomed Pharmacother 2004;58:505-508.
109. Tebas P, Powderly WG, Claxton S, Marin D, Tantisiriwat W, Teitelbaum SL, Yarasheski KE. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS (London, England) 2000;14:F63-F67.
110. Brown TT, Ruppe MD, Kassner R, Kumar P, Kehoe T, Dobs AS, Timpone J. Reduced bone mineral density in human immunodefi ciency virus-infected patients and its association with increased central adiposity and postload hyperglycemia. J Clin Endocrinol Metab 2004;89:1200-1206.
111. Caron M, Auclairt M, Vissian A, Vigouroux C, Capeau J. Contribution of mitochondrial dysfunction and oxidative stress to cellular premature senescence induced by antiretroviral thymidine analogues. Antiviral Ther 2008;13:27-38.
112. Varanasi SS, Francis RM, Berger CE, Papiha SS, Datta HK. Mitochondrial DNA deletion associated oxidative stress and severe male osteoporosis. Osteoporos Int 1999;10:143-149.
113. Chariot P, Drogou I, de Lacroix-Szmania I, Eliezer-Vanerot MC, Chazaud B, Lombes A, Schaeffer A, Zafrani ES. Zidovudineinduced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. J Hepatol 1999;30:156-160.
114. Carr A, Miller J, Eisman JA, Cooper DA. Osteopenia in HIVinfected men: Association with asymptomatic lactic acidemia and lower weight pre-antiretroviral therapy. AIDS (London, England) 2001;15:703-709.
115. Huang JS, Rietschel P, Hadigan CM, Rosenthal DI, Grinspoon S. Increased abdominal visceral fat is associated with reduced bone density in HIV-infected men with lipodystrophy. AIDS 2001;15:975-982.
116. von Muhlen D, Safi i S, Jassal SK, Svartberg J, Barrett-Connor E. Associations between the metabolic syndrome and bone health in older men and women: The Rancho Bernardo Study. Osteoporos Int 2007;18:1337-1344.
117. Ahmed LA, Schirmer H, Berntsen GK, Fonnebo V, Joakimsen RM. Features of the metabolic syndrome and the risk of non-vertebral fractures: The Tromso study. Osteoporos Int 2006;17:426-432.
118. Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 2007;166:495-505. (Pubitemid 47283633)
119. Huang JS, Mulkern RV, Grinspoon S. Reduced intravertebral bone marrow fat in HIV-infected men. AIDS 2002;16:1265-1269.
120. Wiercinska-Drapalo A, Jaroszewicz J, Tarasow E, Siergiejczyk L, Prokopowicz D. The possible association between serum cholesterol concentration and decreased bone mineral density as well as intravertebral marrow fat in HIV-1 infected patients. Infection 2007;35:46-48.
121. Jain RG, Lenhard JM. Select HIV protease inhibitors alter bone and fat metabolism ex vivo. J Biol Chem 2002;277:19247-19250.
122. Grinspoon SK, Grunfeld C, Kotler DP, Currier JS, Lundgren JD, Dube MP, Lipshultz SE, Hsue PY, Squires K, Schambelan M, Wilson PW, Yarasheski KE, Hadigan CM, Stein JH, Eckel RH. State of the science conference: Initiative to decrease cardiovascular risk and increase quality of care for patients living with HIV/AIDS: Executive summary. Circulation 2008;118:198-210.