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Potential Therapies for the HIV-Associated Lipodystrophy Syndrome

  • Christine A. Wanke

Abstract

The HIV associated liposdystrophy syndrome consists of four parts that are likely to be related, but that appear to be able to exist independently in an HIV-infected individual (1, 2, 3, 4, 5, 6). These four components include: fat deposition (buffalo hump, visceral fat, breast enlargement), subcutaneous fat atrophy, disorders of glucose and insulin metabolism, most commonly manifest as glucose intolerance, and disorders of lipid and cholesterol metabolism, with elevations in total cholesterol, fasting triglycerides, and low density lipoprotein cholesterol (non-HDL cholesterol). The epidemiology and potential mechanisms for these are discussed in detail in other chapters in this book. It is clear that both of the body shape abnormalities are distressing to patients, and have lead to refusal to initiate anti-retroviral therapy or termination of ART by patients. In non-HIV-infected patients, visceral fat has a strong association with glucose intolerance and adverse cardiovascular events (7). In population studies, elevations in cholesterol and triglycerides and glucose intolerance/insulin resistance are associated with adverse outcomes as well (8, 9, 10, 11, 12). No definitive studies exist yet for HIV to assure us that the same ourcomes will occur with these metabolic abnormalities in the HIV infected patient, but there is sufficient concern that these association will hold, that interventions to attempt to control these metebolic abnormalities are being investigated.

Keywords

Recombinant Human Growth Hormone Protease Inhibitor Therapy Lipodystrophy Syndrome Buffalo Hump Body Shape Change 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Lo JC, Mulligan K, Tai VW, Algren H, Schambelan M. Buffalo Hump in men with HIV-1 infections. Lancet 1998; 351: 867–870.PubMedCrossRefGoogle Scholar
  2. 2.
    Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, Cooper DA. A syndrome of peripheral lipodystophy, hyperinsulinemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12 F51–58.CrossRefGoogle Scholar
  3. 3.
    Miller KD, Jones E, Yanovski JA, Shankar R, Feuerstein I, Falloon J. Visceral abdominal-fat accumulation assocaited with the use of indinavir. Lancet 1998; 351: 871–875.PubMedCrossRefGoogle Scholar
  4. 4.
    Walli R, Herfort O, Michl, Demant T, Jager H, Dieterle C, Bogner JR, Landgraf R, Goebel FD. Treatment with protease inhibitors associated with peripheral insulin resistance and impaired glucose tolerance in HIV-1 infected patients. AIDS 1998; 12: F167–173.CrossRefGoogle Scholar
  5. 5.
    Dube MP. Disorders of glucose metabolism in patients infected with human immunodeficiency virus. Clin Infectious Disease 2000; 31: 1467–1475.CrossRefGoogle Scholar
  6. 6.
    Safrin S, Grunfeld C. Fat distribution and metabolic changes in patients with HIV infection. AIDS 1999; 13:2493–2505.PubMedCrossRefGoogle Scholar
  7. 7.
    Bjorntorp P. Abdominal obesity and the development of non-insulin dependent diabetes mellitus. Diabetes Metab Rev 1998; 4: 615–622.CrossRefGoogle Scholar
  8. 8.
    Larsson B, Svardsudd K, Welin L, Wilhelmson L, Bjorntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: a 13 year follow-up of participants in the study of men born in 1913. BM J 1984; 288: 1401–1404.CrossRefGoogle Scholar
  9. 9.
    Pyorala M, Miettinen H, Laasko M, Puorala K. Hyperinsulinemia predicts coronary heart disease risk in healthy middle aged men: the 22 year follow up results of the Helsinki Policeman Study. Circulation 1998; 98: 398–404.PubMedCrossRefGoogle Scholar
  10. 10.
    Lean MEJ, Han TS, Seidell JC. Impairment of health and quality of life in people with large waist circumference. Lancet 1998; 351: 853–856.PubMedCrossRefGoogle Scholar
  11. 11.
    Seidell JC, Han TS, Feskens JM, Lean MEJ: Narrow hips and broad waist circumferences independently contribute to increased risk of non-insulin dependent diabetes mellitus. J internal Med 1997;242:401–406.PubMedCrossRefGoogle Scholar
  12. 12.
    Ohlson LO, Larsson B, Svardsudd K, Welin L, Erikson H, Wihelmsen L, Bjorntorp P, Tibblin G. The influence of body fat distribution on the incidence of diabetes mellitus. Diabetes 1985; 34: 1055–1058.PubMedCrossRefGoogle Scholar
  13. 13.
    Lichtenstein K, Ward D, Delaney K, Moorman A, Palella F, Young B, Wood K, Holmberg S. Clinical factors related to the severity of fat redistribution in the HIV outpatient study. 7th CROI, San Francisco, CA 2000.Google Scholar
  14. 14.
    Gerrior J, Kantaros J, Coakley E, Albrecht M, Wanke C. The fat redistribution syndrome in patients infected with HIV: measurements of body shape abnormalities. Journal of the American Dietetic Association 2001; 101: 1175–1180.PubMedCrossRefGoogle Scholar
  15. 15.
    Wood PD, Stefanick ML, Dreon DM, Frey-Hewitt B, Garay SC, Williams PT, Superko HR, Fortmann SP, Albers JJ, Vranizan KM, Ellsworth NM, Terry RB, Haskell WL. Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise. NEJM 1988; 319: 173–179.CrossRefGoogle Scholar
  16. 16.
    Wood PD, Stefanick ML, Williams PT, Haskell WL. The effects of plasma lipoproteins of a prudent weight reducing diet, withor without exercise, in overweight men and women. NEJM 1991;325:461–466.PubMedCrossRefGoogle Scholar
  17. 17.
    Wolver Tm, Jenkins DJ, Vuksan V, Jenkins AL, Wong GS, Josse RG. Benenflcial effect of low-glycemic index diet in overweight NIDDM subjects. Diabetes Care 1992; 15: 562–564.CrossRefGoogle Scholar
  18. 18.
    Saint-Marc T, Tournaine J. Effects of metformin on insulin resistance and central adiposity in patients receiving effective protease inhibitor therapy. AIDS 1999; 13: 1000–1002.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCrossRefGoogle Scholar
  20. 20.
    Roubenoff R, Weiss L, McDermott A, Heflin T, Cloutier GJ, Wood M, Gorbach SL. A pilot sutdy of exercise training to reduce trunk fat in adults with HIV-associated fat redistribution. AIDS 1999; 13: 1373–1375.PubMedCrossRefGoogle Scholar
  21. 21.
    Wanke CA, Gerrior J, Kantaros J, Coakley E, Albrecht M. Recombinant human growth hormone improves the fat redistribution syndrome in patients with HIV. AIDS 1999; 13: 2099–2103.PubMedCrossRefGoogle Scholar
  22. 22.
    Torres RA, Unger KW, Cadman J A, Kaaous JY. Recombinant human growth hormone improved truncal adiposity and buffalo humps in HIV positive patients on HA ART. AIDS 1999; 13:2479–2481.PubMedCrossRefGoogle Scholar
  23. 23.
    Engelson ES, Glesby M, Shikan J et al. Effest of recombinant human growth hormone on the treatment of visceral fat accumulation in HIV infection: J AIDS 2002; 30: 379–391.Google Scholar
  24. 24.
    Wolfert FG, Cetrulo CL, Nevarre DR. Suction assisted Lipectomy for lipodystrophy syndromes attributed to HIV-protease inhibitor use. Plastic and Reconstruction Surgery 1999; 104:1814–1820.CrossRefGoogle Scholar
  25. 25.
    Khanlou H, Adair M, Farthing C. Reduction of buffalo hump by switching to amprenavir in an HIV-infected patient. Archives Int Med 2000; 160: 3499–3500.CrossRefGoogle Scholar
  26. 26.
    Martinez E, Conget I, Loranzo L, Casamitjana R, Gatell JM. Reversion of metabolic abnormalities after swtiching from HIV-1 protease inhibitors to neviripine. AIDS 1999; 13:805–810.PubMedCrossRefGoogle Scholar
  27. 27.
    Marin P, Holmang S, Jonsson L, Sjostrom L, Kvist H, Holm G, Lindstedt G, Bjorntorp P. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obesity Relat Metab Disord 1992; 16: 991–997.Google Scholar
  28. 28.
    Dieterich D, Aymat R, Braun J, Mullen M, McMeeking A, Weisz K, Kreiswirth K, O’Brien K, Lawson, Hergenroeder P, Tirelli R. Incidence of body habitus changes in a cohort of 725 HIV-infected patients. 6th CROI, Chicago, Illinois 1999.Google Scholar
  29. 29.
    Arioglu E, Duncan-Morin J, Sebring N et al. Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Annals Internal Med 2000; 133: 263–274.Google Scholar
  30. 30.
    Stobel M, Muller P, Claudel P. Complete reversibility of severe nucleoside induced lipodystrophy. AIDS 1999; 13: 2606–2608.CrossRefGoogle Scholar
  31. 31.
    Barreiro P, Soriano V, Blanco F, Casimiro C, 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.PubMedCrossRefGoogle Scholar
  32. 32.
    Carr A, Workman C, Smith DE, Hoy J, et al. Abacavir subsitution for thymidine nucleoside analogues in HIV-infected patients with lipoatrophy: a randomized, controlled, open-label multicenter, 24 week study. JAMA, 2002; 288: 207–215.PubMedCrossRefGoogle Scholar
  33. 33.
    Noor MA, Lo JC, Mulligan K, Schwartz JM, Halvorsen RA, Schambelan M, Grundfeld C. Metabolic effects of indinavir in healthy HIV-seronegative men. AIDS 2001; 15: F 11–18.CrossRefGoogle Scholar
  34. 34.
    Noor MA, Seneviratne T, Aweeka FT, Lo JC, Schwarz JM, Mulligan K, Schambelan M, Grunfeld C. Inidinavir acutely inhibits insulin stimulated glucose disposal in humans: a randomized placebo controlled study. AIDS 2002; 16: F1–8.CrossRefGoogle Scholar
  35. 35.
    NCEP: 2nd report of the expert panel on detection, evaluation and treatment of high blood cholesterol in adults. Circulation 1994; 89: 1333–1445.CrossRefGoogle Scholar
  36. 36.
    Dube MP, Sprecher D, Henry WK, Aberg JA, Torrinani FJ, Hodis HN, Scouten J, Levin J, Myers G, Zachin R, Nevin T, Currier JS. Preliminary Guidelines for he evaluation and management of dyslipidemia in adults infected with the human immunodeficiency virus and receiving antiretroviral therapy. Clinical Infectious Disease 2000; 31: 1216–1224.CrossRefGoogle Scholar
  37. 37.
    Henry K, Melroe H, Huebesch J, Hermundson J, Simson J. Atorvastatin and gemfibrozil for protease inhibitor related abnormalities. Lancet 1998; 352: 1031–1032.PubMedCrossRefGoogle Scholar
  38. 38.
    Sullivan AK, Nelson MR. Marked hyperlipidemia on ritonavir therapy. AIDS 1997; 11: 938–939.PubMedCrossRefGoogle Scholar
  39. 39.
    Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, Lo JC, Schambelan M. Hyperlidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquired Immune Deficiency Syndrome 2000; 23: 35–43.Google Scholar
  40. 40.
    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 2000; 14:51–57.PubMedCrossRefGoogle Scholar
  41. 41.
    Murphy R, Brun S, King M, et al. Kaletra in ART naïve subjects: 4 year follow up study M97-720. Abstract H-165,42nd ICAAC, San Diego, California, 2002.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Christine A. Wanke
    • 1
  1. 1.Departments of Medicine and Community HealthTufts University School of MedicineBostonUSA

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