AIDS-related lipodystrophy/insulin resistance syndrome

Hormone and Metabolic Research

Volumn 35, Issue 3, 2003, Pages 129-136

  Kino, T ^a   Mirani, M ^a   Alesci, S ^a   Chrousos, G P ^a  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

Author keywords

Adipose Calls; AIDS; Fat Distribution; Pseudo Cushing

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE; ALPHA INTERFERON; ANTIVIRUS AGENT; APOLIPOPROTEIN B; ATORVASTATIN; CORTICOTROPIN; CYCLIN T1; CYTOKINE; GEMFIBROZIL; GLUCOCORTICOID; GLUCOSE TRANSPORTER 4; GROWTH HORMONE; HYDROCORTISONE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERLEUKIN 1; INTERLEUKIN 6; LEPTIN; LOW DENSITY LIPOPROTEIN RECEPTOR; METFORMIN; MITOCHONDRIAL DNA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROTEINASE INHIBITOR; REACTIVE OXYGEN METABOLITE; RETINOIC ACID BINDING PROTEIN; RNA DIRECTED DNA POLYMERASE INHIBITOR; STEROL REGULATORY ELEMENT BINDING PROTEIN; TRANSACTIVATOR PROTEIN; TUMOR NECROSIS FACTOR ALPHA; VPR PROTEIN; ZIDOVUDINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ADRENAL FUNCTION; ATHEROSCLEROSIS; BODY FAT; CALORIC INTAKE; CARBOHYDRATE INTOLERANCE; CARDIOVASCULAR RISK; CLINICAL FEATURE; CUSHING SYNDROME; CYTOKINE PRODUCTION; DIABETES MELLITUS; DISEASE ASSOCIATION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA REPLICATION; DYSLIPIDEMIA; ENZYME ACTIVITY; GENE MUTATION; GLUCOSE METABOLISM; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HYPERLIPIDEMIA; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIFE EXPECTANCY; LIPID METABOLISM; LIPODYSTROPHY; LIPOMATOSIS; LONG TERMINAL REPEAT; MORTALITY; MYOPATHY; MYOSITIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUALITY OF LIFE; REVIEW; RHABDOMYOLYSIS; SIDE EFFECT; SIGNAL TRANSDUCTION; TARGET ORGAN; TRIACYLGLYCEROL BLOOD LEVEL;

11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1; ACQUIRED IMMUNODEFICIENCY SYNDROME; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CYTOKINES; GENE PRODUCTS, TAT; GENE PRODUCTS, VPR; GLUCOCORTICOIDS; HIV PROTEASE INHIBITORS; HIV-ASSOCIATED LIPODYSTROPHY SYNDROME; HUMANS; METABOLIC SYNDROME X; MITOCHONDRIAL DISEASES;

DNA VIRUSES; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 0037617482     PISSN: 00185043     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2003-39072     Document Type: Review

References (110)

1. Pantaleo G, Graziosi C, Fauci AS. New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 1993; 328: 327-335
2. Tashima KT, Flanigan TP. Antiretroviral therapy in the year 2000. Infect Dis Clin North Am 2000; 14: 827-849
3. Morris AS, Cu-Uvin S, Harwell JI, Garb J, Zorrilla C, Vajaranant M, Dobles AR, Jones TB, Carlan S, Allen DY. Multicenter review of protease inhibitors in 89 pregnancies. J Acquir Immune Defic Syndr 2000; 25: 306-311
4. Kaufmann GR, Cooper DA. Antiretroviral therapy of HIV-1 infection: established treatment strategies and new therapeutic options. Curr Opin Microbiol 2000; 3: 508-514
5. Harrington M, Carpenter CC. Hit HIV-1 hard, but only when necessary. Lancet 2000; 355: 2147-2152
6. Vella S, Palmisano L. Antiretroviral therapy: state of the HAART. Antiviral Res 2000; 45: 1-7
7. de Luca A, Murri R, Damiano F, Ammassari A, Antinori A. "Buffalo hump" in HIV-1 infection. Lancet 1998; 352: 320
8. Miller KK, Daly PA, Sentochnik D, Doweiko J, Samore M, Basgoz NO, Grinspoon SK. Pseudo-Cushing's syndrome in human immunodeficiency virus-infected patients. Clin Infect Dis 1998; 27: 68-72
9. Lo JC, Mulligan K, Tai VW, Algren H, Schambelan M. "Buffalo hump" in men with HIV-1 infection. Lancet 1998; 351: 867-870
10. Stocker DN, Meier PJ, Stoller R, Fattinger KE. "Buffalo hump" in HIV-1 infection. Lancet 1998; 352: 320-321
11. Saint-Marc T, Touraine JL. "Buffalo hump" in HIV-1 infection. Lancet 1998; 352: 319-320
12. Christeff N, Melchior JC, de Truchis P, Perronne C, Nunez EA, Gougeon ML. Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations. AIDS 1999; 13: 2251-2260
13. Dornier C, Posth M, Granel F, Barbaud A, Schmutz JL. "Buffalo hump" related to indinavir treatment. Ann Dermatol Venereol 1999; 126: 720-722
14. Graham NM. Metabolic disorders among HIV-infected patients treated with protease inhibitors: a review. J Acquit Immune Defic Syndr 2000; 25: 4-11
15. Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000; 356: 1423-1430
16. Behrens GM, Stoll M, Schmidt RE. Lipodystrophy syndrome in HIV infection: what is it, what causes it and how can it be managed? Drug Saf 2000; 23: 57-76
17. Qaqish RB, Fisher E, Rublein J, Wohl DA. HIV-associated lipodystrophy syndrome. Pharmacotherapy 2000; 20: 13-22
18. Hadigan C, Meigs JB, Corcoran C, Rietschel P, Piecuch S, Basgoz N, Davis B, Sax P, Stanley T, Wilson PW, D'Agostino RB, Grinspoon S. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001; 32: 130-139
19. Jain RG, Furfine ES, Pedneault L, White AJ, Lenhard JM. Metabolic complications associated with antiretroviral therapy. Antiviral Res 2001; 51: 151-177
20. 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
21. Beisiegel U, Weber W, Ihrke G, Herz J, Stanley KK. The LDL-receptor-related protein, LRP, is an apolipoprotein E-binding protein. Nature 1989; 341: 162-164
22. Erkelens DW. Metabolic basis for hypertriglyceridaemia in familial combined hyperlipidaemia. Eur Heart J 1998; 19 Suppl H: H23-26
23. Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J 1996; 10: 940-954
24. Schutt M, Meier M, Meyer M, Klein J, Aries SP, Klein HH. The HIV-1 protease inhibitor indinavir impairs insulin signalling in HepG2 hepatoma cells. Diabetologia 2000; 43: 1145-1148
25. Petit JM, Duong M, Duvillard L, Piroth L, Grappin M, Verges B, Chavanet P, Brun JM, Pottier H. 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: 367-372
26. Lenhard JM, Weiel JE, Paulik MA, Furfine ES. Stimulation of vitamin A(1) acid signaling by the HIV protease inhibitor indinavir. Biochem Pharmacol 2000; 59: 1063-1068
27. Nguyen AT, Gagnon A, Angel JB, Sorisky A. Ritonavir increases the level of active ADD-1/SREBP-1 protein during adipogenesis. AIDS 2000; 14: 2467-2473
28. Dowell P, Flexner C, Kwiterovich PO, Lane MD. Suppression of preadipocyte differentiation and promotion of adipocyte death by HIV protease inhibitors. J Biol Chem 2000; 275: 41 325-41 332
29. Cossarizza A, Mussini C, Vigano A. Mitochondria in the pathogenesis of lipodystrophy induced by anti-HIV antiretroviral drugs: actors or bystanders? BioEssays 2001; 23: 1070-1080
30. Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem 2000; 275: 20251-20254
31. Jiminez-Exposito MJ, Paul A, Laville A, Masana L. Non-activity of hepatic lipase during a treatment with ritonavirProceedings of the 6th European Conference on Clinical Aspects and Treatment of HIV Infection Hamberg, Germany: 1997
32. Zhang B, MacNaul K, Szalkowski D, Li Z, Berger J, Moller DE. Inhibition of adipocyte differentiation by HIV protease inhibitors. J Clin Endocrinol Metab 1999; 84: 4274-4277
33. Lenhard JM, Furfine ES, Jain RG, Ittoop O, Orband-Miller LA, Blanchard SG, Paulik MA, Weiel JE. HIV protease inhibitors block adipogenesis and increase lipolysis in vitro. Antiviral Res 2000; 47: 121-129
34. Wentworth JM, Burris TP, Chatterjee VK. HIV protease inhibitors block human preadipocyte differentiation, but not via the PPARgamma/RXR heterodimer. J Endocrinol 2000; 164: R7-10
35. Baldo A, Sniderman AD, St-Luce S, Avramoglu RK, Maslowska M, Hoang B, Monge JC, Bell A, Mulay S, Cianflone K. The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis. J Clin Invest 1993; 92: 1543-1547
36. Liang JS, Distler O, Cooper DA, Jamil H, Deckelbaum RJ, Ginsberg HN, Sturley SL. 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
37. Behrens G, Schmidt HH, Stoll M, Schmidt RE. ApoE genotype and protease-inhibitor-associated hyperlipidaemia. Lancet 1999; 354: 76
38. 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 antiretroviral-therapy-related lipodystrophy. Lancet 1999; 354: 1112-1115
39. Ujpal M, Nemeth ZS, Reichwein A, Szabo GY. Long-term results following surgical treatment of benign symmetric lipomatosis (BSL). Int J Oral Maxillofac Surg 2001; 30: 479-483
40. Klopstock T, Naumann M, Seibel P, Shalke B, Reiners K, Reichmann H. Mitochondrial DNA mutations in multiple symmetric lipomatosis. Mol Cell Biochem 1997; 174: 271-275
41. Klopstock T, Naumann M, Schalke B, Bischof F, Seibel P, Kottlors M, Eckert P, Reiners K, Toyka KV, Reichmann H. Multiple symmetric lipomatosis: abnormalities in complex IV and multiple deletions in mitochondrial DNA. Neurology 1994; 44: 862-866
42. Brinkman K, ter Hofstede HJ, Burger DM, Smeitink JA, Koopmans PP. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 1998; 12: 1735-1744
43. Dalakas MC, Illa I, Pezeshkpour GH, Laukaitis JP, Cohen B, Griffin JL. Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med 1990; 322: 1098-1105
44. Flomenbaum M, Soeiro R, Udem SA, Kress Y, Factor SM. Proliferative membranopathy and human immunodeficiency virus in AIDS hearts. J Acquit Immune Defic Syndr 1989; 2: 129-135
45. Yanovski JA, Miller KD, Kino T, Friedman TC, Chrousos GP, Tsigos C, Falloon J. Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. J Clin Endocrinol Metab 1999; 84: 1925-1931
46. Shikuma C, Hu N, Milne C, Yost F, Shimizu S, Shiramizu B. Analysis of subcutaneous adipose tissue mitochondrial DNA from individuals with HARRT-associated lipodystrophy8th Conference on Retroviruses and Opportunistic Infections Chicago: 2001: 244
47. Ledru E, Christeff N, Patey O, de Truchis P, Melchior JC, Gougeon ML. Alteration of tumor necrosis factor-alpha T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus-associated lipodystrophy syndrome. Blood 2000; 95: 3191-3198
48. Sethi JK, Hotamisligil GS. The role of TNF alpha in adipocyte metabolism. Semin Cell Dev Biol 1999; 10: 19-29
49. Chrousos GP. The stress response and immune function: clinical implications. The 1999 Novera H. Spector Lecture. Ann N Y Acad Sci 2000; 917: 38-67
50. Orban Z, Remaley AT, Sampson M, Trajanoski Z, Chrousos GP. The differential effect of food intake and beta-adrenergic stimulation on adipose-derived hormones and cytokines in man. J Clin Endocrinol Metab 1999; 84: 2126-2133
51. Vgontzas AN, Papanicolaou DA, Bixler EO, Hopper K, Lotsikas A, Lin HM, Kales A, Chrousos GP. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 2000; 85: 1151-1158
52. Christeff N, Melchior JC, de Truchis P, Perronne C, Gougeon ML. Increased serum interferon alpha in HIV-1 associated lipodystrophy syndrome. Eur J Clin Invest 2002; 32: 43-50
53. Feingold KR, Grunfeld C. Role of cytokines in inducing hyperlipidemia. Diabetes 1992; 41 Suppl. 2: 97-101
54. Grimble RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care 2002; 5: 551-559
55. Graham NM. Metabolic disorders among HIV-infected patients treated with protease inhibitors: a review. J Acquit Immune Defic Syndr 2000; 25: S4-S11
56. Moyle G. Mitochondrial toxicity hypothesis for lipoatrophy: a refutation. AIDS 2001; 15: 413-415
57. Diederich S, Grossmann C, Hanke B, Quinkler M, Herrmann M, Bahr V, Oelkers W. In the search for specific inhibitors of human 11beta-hydroxysteroid-dehydrogenases (11beta-HSDs): chenodeoxycholic acid selectively inhibits 11beta-HSD-I. Eur J Endocrinol 2000; 142: 200-207
58. Seckl JR, Walker BR. Minireview: 11beta-hydroxysteroid dehydrogenase type 1 - a tissue-specific amplifier of glucocorticoid action. Endocrinology 2001; 142: 1371-1376
59. Tomlinson JW, Moore J, Cooper MS, Bujalska I, Shahmanesh M, Burt C, Strain A, Hewison M, Stewart PM. Regulation of expression of 11betahydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines. Endocrinology 2001; 142: 1982-1989
60. Escher G, Galli I, Vishwanath BS, Frey BM, Frey FJ. Tumor necrosis factor alpha and interleukin 1beta enhance the cortisone/cortisol shuttle. J Exp Med 1997; 186: 189-198
61. Pavlakis GN. The molecular biology of HIV-1, AIDS: Diagnosis, Treatment and Prevention. DeVita VT, Hellman S, Rosenberg SA (eds). Philadelphia: Lippincott Raven, 1996; 4 Edition: 45-74
62. Cohen EA, Subbramanian RA, Gottlinger HG. Role of auxiliary proteins in retroviral morphogenesis. Curr Top Microbiol Immunol 1996; 214: 219-235
63. Emerman M. HIV-1, Vpr and the cell cycle. Curr Biol 1996; 6: 1096-1103
64. Stewart SA, Poon B, Jowett JB, Xie Y, Chen IS. Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells. Proc Natl Acad Sci U S A 1999; 96: 12039-12043
65. Ayyavoo V, Mahalingam S, Rafaeli Y, Kudchodkar S, Chang D, Nagashunmugam T, Williams WV, Weiner DB. HIV-1 viral protein R (Vpr) regulates viral replication and cellular proliferation in T cells and monocytoid cells in vitro. J Leukoc Biol 1997; 62: 93-99
66. Goh WC, Rogel ME, Kinsey CM, Michael SF, Fultz PN, Nowak MA, Hahn BH, Emerman M. HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat Med 1998; 4: 65-71
67. Gibbs JS, Lackner AA, Lang SM, Simon MA, Sehgal PK, Daniel MD, Desrosiers RC. Progression to AIDS in the absence of a gene for vpr or vpx. J Virol 1995; 69: 2378-2383
68. Sawaya BE, Khalili K, Gordon J, Taube R, Amini S. Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. J Biol Chem 2000; 275: 35209-35214
69. He J, Choe S, Walker R, di Marzio P, Morgan DO, Landau NR. Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol 1995; 69: 6705-6711
70. Jowett JB, Planelles V, Poon B, Shah NP, Chen ML, Chen IS. The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle. J Virol 1995; 69: 6304-6313
71. Re F, Braaten D, Franke EK, Luban J. Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B. J Virol 1995; 69: 6859-6864
72. Heinzinger NK, Bukinsky MI, Haggerty SA, Ragland AM, Kewalramani V, Lee MA, Gendelman HE, Ratner L, Stevenson M, Emerman M. The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc Natl Acad Sci U S A 1994; 91: 7311-7315
73. Vodicka MA, Koepp DM, Silver PA, Emerman M. HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes Dev 1998; 12: 175-185
74. Popov S, Rexach M, Zybarth G, Reiling N, Lee MA, Ratner L, Lane CM, Moore MS, Blobel G, Bukrinsky M. Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. EMBO J 1998; 17: 909-917
75. Levy DN, Refaeli Y, Weiner DB. Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency. J Virol 1995; 69: 1243-1252
76. Henklein P, Bruns K, Sherman MP, Tessmer U, Licha K, Kopp J, de Noronha CM, Greene WC, Wray V, Schubert U. Functional and structural characterization of synthetic HIV-1 vpr that transduces cells, localizes to the nucleus, and induces G2 cell cycle arrest. J Biol Chem 2000; 275: 32016-32026
77. Kino T, Gragerov A, Kopp JB, Stauber RH, Pavlakis GN, Chrousos GP. The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor. J Exp Med 1999; 189: 51-62
78. Kino T, Gragerov A, Slobodskaya O, Tsopanomichalou M, Chrousos GP, Pavlakis GN. Human immunodeflciency virus type-1 (HIV-1) accessory protein Vpr induces transcription of the HIV-1 and glucocorticoid-responsive promoters by binding directly to p300/CBP coactivators. J Virol 2002; 76: 9724-9734
79. Wei P, Garber ME, Fang SM, Fischer WH, Jones KA. A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell 1998; 92: 451-462
80. Kino T, Slobodskaya O, Pavlakis GN, Chrousos GP. Nuclear receptor coactivator p160 proteins enhance the HIV-1 long terminal repeat promoter by bridging promoter-bound factors and the Tat-P-TEFb complex. J Biol Chem 2002; 277: 2396-2405
81. Fawell S, Seery J, Daikh Y, Moore C, Chen LL, Pepinsky B, Barsoum J. Tat-mediated delivery of heterologous proteins into cells. Proc Natl Acad Sci U S A 1994; 91: 664-668
82. Willson TM, Lambert MH, Kliewer SA. Peroxisome proliferator-activated receptor gamma and metabolic disease. Annu Rev Biochem 2001; 70: 341-367
83. Jacob S, Stumvoll M, Becket R, Koch M, Nielsen M, Loblein K, Maerker E, Volk A, Renn W, Balletshofer B, Machicao F, Rett K, Haring HU. The PPARgamma2 polymorphism pro12Ala is associated with better insulin sensitivity in the offspring of type 2 diabetic patients. Horm Metab Res 2000; 32: 413-416
84. Shrivastav S, Kino T, Chrousos GP, Kopp JB. HIV-1 Vpr binds and inhibits pPAR-g: Implications for HIV-associated Insulin resistance and lipodystrophy2000 International Meeting of the Institute of Human Virology Baltimore, MA: 2000
85. Kino T, Chrousos GP. Acquired immunodeficiency syndrome-related insulin resistance and lipodystrophy: a multifactorial viral and iatrogenic condition. Endocr Pract 2001; 7: 480-484
86. Kino T, Gragerov A, Pavlakis GN, Chrousos GP. HIV-1 accessory protein Vpr antagonizes insulin"s effect on the cytosolic translocation of FKHR and promotes its transcriptional activity: potential contribution of Vpr to insulin resistance of AIDS patients. 83rd Endocrine Society Annual Meeting Denver: 2001: 95
87. Nakae J, Barr V, Accili D. Differential regulation of gene expression by insulin and IGF-1 receptors correlates with phosphorylation of a single amino acid residue in the forkhead transcription factor FKHR. EMBO J 2000; 19: 989-996
88. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999; 96: 857-868
89. Green ML. Evaluation and management of dyslipidemia in patients with HIV infection. J Gen Intern Med 2002; 17: 797-810
90. Negredo E, Ribalta J, Paredes R, Ferre R, Sirera G, Ruiz L, Salazar J, Reiss P, Masana L, Clotet B. Reversal of atherogenic lipoprotein profile in HIV-1 infected patients with lipodystrophy after replacing protease inhibitors by nevirapine. AIDS 2002; 16: 1383-1389
91. Wensing AM, Reedijk M, Richter C, Boucher CA, Borleffs JC. Replacing ritonavir by nelfinavir or nelfinavir/saquinavir as part of highly active antiretroviral therapy leads to an improvement of triglyceride levels. AIDS 2001; 15: 2191-2193
92. Walli RK, Michl GM, Bogner JR, Goebel FD. Improvement of HAART-associated insulin resistance and dyslipidemia after replacement of protease inhibitors with abacavir. Eur J Med Res 2001; 6: 413-421
93. Barreiro P, Soriano V, Blanco F, Casimiro C, de la Cruz JJ, Gonzalez-Lahoz J. Risks and benefits of replacing protease inhibitors by nevirapine in HIV-infected subjects under long-term successful triple combination therapy. AIDS 2000; 14: 807-812
94. Henry K, Melroe H, Huebesch J, Hermundson J, Simpson J. Atorvastatin and gemfibrozil for protease-inhibitor-related lipid abnormalities. Lancet 1998; 352: 1031-1032
95. Moyle GJ, Lloyd M, Reynolds B, Baldwin C, Mandalia S, Gazzard BG. Dietary advice with or without pravastatin for the management of hypercholesterolaemia associated with protease inhibitor therapy. AIDS 2001; 15: 1503-1508
96. Miller J, Brown D, Amin J, Kent-Hughes J, Law M, Kaldor J, Cooper DA, Carr A. A randomized, double-blind study of gemfibrozil for the treatment of protease inhibitor-associated hypertriglyceridaemia. AIDS 2002; 16: 2195-2200
97. Murillas J, Martin T, Ramos A, Portero JL. Atorvastatin for protease inhibitor-related hyperlipidaemia. AIDS 1999; 13: 1424-1425
98. Baldini F, di Giambenedetto S, Cingolani A, Murri R, Ammassari A, de Luca A. Efficacy and tolerability of pravastatin for the treatment of HIV-1 protease inhibitor-associated hyperlipidaemia: a pilot study. AIDS 2000; 14: 1660-1662
99. Fichtenbaum CJ, Gerber JG. Interactions Between Antiretroviral Drugs and Drugs Used for the Therapy of the Metabolic Complications Encountered During HIV Infection. Clin Pharmacokinet 2002; 41: 1195-1211
100. Hadigan C, Corcoran C, Basgoz N, Davis B, Sax P, Grinspoon S. Metformin in the treatment of HIV lipodystrophy syndrome: A randomized controlled trial. JAMA 2000; 284: 472-477
101. Hadigan C, Meigs JB, Rabe J, D'Agostino RB, Wilson PW, Lipinska I, Tofler GH, Grinspoon SS. Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance. J Clin Endocrinol Metab 2001; 86: 939-943
102. Hadigan C, Miller K, Corcoran C, Anderson E, Basgoz N, Grinspoon S. Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women. J Clin Endocrinol Metab 1999; 84: 1932-1937
103. Hadigan C, Rabe J, Grinspoon S. Sustained benefits of metformin therapy on markers of cardiovascular risk in human immunodeficiency virus-infected patients with fat redistribution and insulin resistance. J Clin Endocrinol Metab 2002; 87: 4611-4615
104. Alessi MC, Morange P, Juhan-Vague I. Fat cell function and fibrinolysis. Horm Metab Res 2000; 32: 504-508
105. Gervasoni C, Ridolfo AL, Rovati L, Vaccarezza M, Cassana L, Galli M. Maintenance of breast size reduction after mastoplasty and switch to a protease inhibitor-sparing regimen in an HIV-positive woman with highly active antiretroviral therapy-associated massive breast enlargement. AIDS Patient Care STDS 2002; 16: 307-311
106. Talmor M, Hoffman LA, LaTrenta GS. Facial atrophy in HIV-related fat redistribution syndrome: anatomic evaluation and surgical reconstruction. Ann Plast Surg 2002; 49: 11-17
107. Walther RA. Facial lipodystrophy in patients with HIV infections troublesome to treat, Lakartidningen 2002; 99: 3826-3829
108. Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, Wagner AJ, DePaoli AM, Reitman ML, Taylor SI, Gorden P, Garg A. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002; 346: 570-578
109. Estrada V, Serrano-Rios M, Martinez LarradMT, Villar NG, Gonzalez Lopez A, Tellez MJ, Fernandez C. Leptin and adipose tissue maldistribution in HIV-infected male patients with predominant fat loss treated with antiretroviral therapy. J Acquir Immune Defic Syndr 2002; 29: 32-40
110. Garg A. Lipodystrophies. Am J Med 2000; 108: 143-152