Adverse metabolic consequences of HIV protease inhibitor therapy: The search for a central mechanism

American Journal of Physiology - Endocrinology and Metabolism

Volumn 280, Issue 4 43-4, 2001, Pages

  Hruz, Paul W ^a   Murata, Haruhiko ^a   Mueckler, Mike ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Adipogenesis; Glucose transport; Human immunodeficiency virus; Lipodystrophy; Metabolic complications

Indexed keywords

GLUCOSE; PROTEINASE INHIBITOR;

ADIPOSE TISSUE; ANTIMICROBIAL THERAPY; GLUCOSE TRANSPORT; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERLIPIDEMIA; INSULIN RESISTANCE; LIPOATROPHY; METABOLIC DISORDER; PATHOGENESIS; PRIORITY JOURNAL; PROTEINASE INHIBITION; REVIEW;

EID: 0034996070     PISSN: 01931849     EISSN: None     Source Type: Journal    
DOI: 10.1152/ajpendo.2001.280.4.e549     Document Type: Review

References (43)

1. Abbott Laboratories. Norvir (ritonavir capsules) Product Monograph. North Chicago, IL, 2000.
2. Bonfanti P, Valsecchi L, Parazzini F, Carradori S, Pusterla L, Fortuna P, Timillero L, Alessi F, Ghiselli G, Gabbuti A, Di Cintio E, Martinelli C, Faggion I, Landonio S, and Quirino T. Incidence of adverse reactions in HIV patients treated with protease inhibitors: a cohort study. Coordinamento Italiano Studio Allergia e Infezione da HIV (CISAI) Group. J Acquir Immune Defic Syndr Hum Retrovirol 23: 236-245, 2000.
3. Bouchard C, Despres JP, and Mauriege P. Genetic and nongenetic determinants of regional fat distribution. Endocr Rev 14: 72-93, 1993.
4. Burant CF, Sreenan S, Hirano K, Tai TA, Lohmiller J, Lukens J, Davidson NO, Ross S, and Graves RA. Troglitazone action is independent of adipose tissue. J Clin Invest 100: 2900-2908, 1997.
5. Carr A, Miller J, Law M, and Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS 14: F25-F32, 2000.
6. Carr A, Samaras K, Chisholm DJ, and Cooper DA. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 351: 1881-1883, 1998.
7. Domingo P, Matias-Guiu X, Pujol RM, Francia E, Lagarda E, Sambeat MA, and Vazquez G. Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy. AIDS 13: 2261-2267, 1999.
8. Dowell P, Flexner C, Kwiterovich PO, and Lane DM. Suppression of preadipocyte differentiation and promotion of adipocyte death by HIV protease inhibitors. J Biol Chem. 275: 41325-41332, 2000.
9. James DE, Strube M, and Mueckler M. Molecular cloning and characterization of an insulin regulatable glucose transporter. Nature 338: 83-87, 1989.
10. Katz EB, Stenbit AE, Hatton K, DePinho R, and Charron MJ. Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature 377: 151-155, 1995.
11. Lenhard JM, Furfine ES, Jain RG, Ittoop O, Orband-Miller LA, Blanchard SG, Paulik MA, and Weiel JE. HIV protease inhibitors block adipogenesis and increase lipolysis in vitro. Antiviral Res 47: 121-129, 2000.
12. Lenhard JM, Weiel JE, Paulik MA, and Furfine ES. Stimulation of vitamin A1 acid signaling by the HIV protease inhibitor indinavir. Biochem Pharmacol 59: 1063-1068, 2000.
13. Madge S, Kinloch-de-Loes S, Mercey D, Johnson MA, and Weller IV. Lipodystrophy in patients naive to HIV protease inhibitors. AIDS 13: 735-737, 1999.
14. Marshall BA, Hansen PA, Ensor NJ, Ogden MA, and Mueckler M. GLUT-1 or GLUT-4 transgenes in obese mice improve glucose tolerance but do not prevent insulin resistance. Am J Physiol Endocrinol Metab 276: E390-E400, 1999.
15. Martinez E, Conget I, Lozano L, Casamitjana R, and Gatell J. Reversion of metabolic abnormalities after switching from HIV-1 protease inhibitors to nevirapine. AIDS 13: 805-810, 1999.
16. Martinez E and Gatell J. Metabolic abnormalities and use of HIV-1 protease inhibitors. Lancet 352: 821-822, 1998.
17. Merck & Co. Crivixan (Indinavir Sulfate) Capsules Product Monograph. West Point, PA, 1997.
18. Moitra J, Mason MM, Olive M, Krylov D, Gavrilova O, Marcus-Samuels B, Feigenbaum L, Lee E, Aoyama T, Eckhaus M, Reitman ML, and Vinson C. Life without white fat: a transgenic mouse. Genes Dev 12: 3168-3181, 1998.
19. Montague CT and O'Rahilly S. The perils of portliness: causes and consequences of visceral adiposity. Diabetes 49: 883-888, 2000.
20. Mueckler M. Glucose transport and glucose homeostasis: new insights from transgenic mice. News Physiol Sci 10: 22-29, 1995.
21. Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, Lo JC, and Schambelan M. 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 Hum Retrovirol 23: 35-43, 2000.
22. Murata H, Hruz PW, and Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem 275: 20251-20254, 2000.
23. Noor M, Lo JC, Mulligan K, Halvorsen R, Schwarz JM, Shambelan M, and Grunfeld C. Metabolic effects of indinavir in healthy HIV-seronegative subjects. Antiviral Therapy 5: 8, 2000.
24. Palella, FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, and Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338: 853-860, 1998.
25. Penzak SR and Chuck SK. Hyperlipidemia associated with HIV protease inhibitor use: pathophysiology, prevalence, risk factors and treatment. Scand J Infect Dis 32: 111-123, 2000.
26. Petit JM, Duong M, Duvillard L, Piroth L, Grappin M, Verges B, Chavanet P, Brun JM, and Portier 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 32: 367-372, 2000.
27. Rosen ED, Walkey CJ, Puigserver P, and Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev 14: 1293-1307, 2000.
28. Rossetti L, Stenbit AE, Chen W, Hu M, Barzilai N, Katz EB, and Charron MJ. Peripheral but not hepatic insulin resistance in mice with one disrupted allele of the glucose transporter type 4 (GLUT4) gene. J Clin Invest 100: 1831-1839, 1997.
29. Safrin S and Grunfeld C. Fat distribution and metabolic changes in patients with HIV infection. AIDS 13: 2493-2505, 1999.
30. Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang J, Gastaut J, and Touraine J. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue tharapy. AIDS 13: 1659-1667, 1999.
31. Saint-Marc T, Partisani M, Poizot-Martin I, Rouviere O, Bruno F, Avellaneda R, Lang J, Gastaut J, and Touraine J. Fat distribution evaluated by computed tomography and metabolic abnormalities in patients undergoing antiretroviral therapy: preliminary results of the LIPOCO study. AIDS 14: 37-49, 2000.
32. Schwarcz SK, Hsu LC, Vittinghoff E, and Katz MH. Impact of protease inhibitors and other antiretroviral treatments on acquired immunodeficiency syndrome survival in San Francisco, California, 1987-1996. Am J Epidemiol 152: 178-185, 2000.
33. Seip M and Trygstad O. Generalized lipodystrophy, congenital and acquired (lipoatrophy). Acta Paediatr Scand 413: 2-28, 1996.
34. Shimomura I, Hammer RE, Richardson JA, Ikemoto S, Bashmakov Y, Goldstein JL, and Brown MS. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev 12: 3182-3194, 1998.
35. Stricker RB and Goldberg B. Fat accumulation and HIV-1 protease inhibitors. Lancet 352: 1392, 1998.
36. Thiebaut R, Dabis F, Malvy D, Jacqmin-Gadda H, Mercie P, and Valentin VD. Serum triglycerides, HIV infection, and highly active antiretroviral therapy, Aquitaine Cohort, France, 1996 to 1998. Groupe d'Epidemiologie Clinique du Sida en Aquitaine (GECSA). J Acquir Immune Defic Syndr Hum Retrovirol 23: 261-265, 2000.
37. Tomasselli AG and Heinrikson RL. Targeting the HIV-protease in AIDS therapy: a current clinical perspective. Biochim Biophys Acta 1477: 189-214, 2000.
38. Tsiodras S, Mantzoros C, Hammer S, and Samore M. Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy: a 5-year cohort study. Arch Intern Med 160: 2050-2056, 2000.
39. Walli R, Michl GM, Muhlbayer D, Brinkmann L, and Goebel FD. Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated diabetes mellitus. Res Exp Med (Berl) 199: 253-262, 2000.
40. Wentworth JM, Burris TP, and Chatterjee VKK. HIV protease inhibitors block human preadipocyte differentiation, but not via the PPAR/RXR heterodimer. J Endocrinol 164: R7-R10, 1999.
41. Yanovski JA, Miller KD, Kino T, Friedman TC, Chrousos GP, Tsigos C, and Falloon J. Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. J Clin Endocrinol Metab 84: 1925-1931, 1999.
42. Ye JM, Samara K, Bonner KM, Cooney DJ, Chisholm DJ, and Kraegen EW. Ritonovir has paradoxical effects on lipid metabolism and insulin sensitivity in rats compared with humans. AIDS 12: 2236-2237, 1998.
43. Zhang B, Macnaul K, Szalkowski D, Li Z, Berger J, and Moller D. Inhibition of adipocyte differentiation by HIV protease inhibitors. J Clin Endocrinol Metab 84: 4274-4277, 1999.