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Summaries for Patients are a service provided by Annals to help patients better understand the complicated and often mystifying language of modern medicine.
SUMMARIES FOR PATIENTS
Rosiglitazone Treatment for Fat Redistribution and Metabolic Abnormalities Caused by Anti-HIV Therapy
18 May 2004 | Volume 140 Issue 10 | Page I-36
Summaries for Patients are presented for informational purposes only. These summaries are not a substitute for advice from your own medical provider. If you have questions about this material, or need medical advice about your own health or situation, please contact your physician. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the American College of Physicians.
The summary below is from the full report titled "Metabolic Effects of Rosiglitazone in HIV Lipodystrophy. A Randomized, Controlled Trial." It is in the 18 May 2004 issue of Annals of Internal Medicine (volume 140, pages 786-794). The authors are C. Hadigan, S. Yawetz, A. Thomas, F. Havers, P.E. Sax, and S. Grinspoon.
What is the problem and what is known about it so far?
Although medications that combat HIV infection (antiretroviral medications) have greatly improved survival and quality of life in patients infected with HIV, they can also produce troublesome side effects. When patients receive certain antiretroviral drugs, doctors frequently observe a change in the way that fat is distributed in the body, an effect that substantially changes the patient's appearance. Fat is lost from the face, arms, legs, and buttocks (lipoatrophy) and is redistributed to the belly, breasts, and back of the neck. The fat redistribution pattern is known as lipodystrophy. Doctors have determined that some of the important reasons for lipodystrophy involve a change in the way the body processes dietary fats and sugars. In addition to interfering with the body's ability to form fat tissue in a normal fashion, antiretroviral drugs decrease the patient's sensitivity to insulin (the hormone that allows cells to use sugar). This effect causes the body to release more insulin into the bloodstream, a condition known as hyperinsulinemia. Hyperinsulinemia also occurs in diabetic people. For this reason, a drug used to treat diabetes (rosiglitazone) has been suggested as a possible way to treat or prevent HIV lipodystrophy.
Why did the researchers do this particular study?
To find out whether rosiglitazone could block hyperinsulinemia and lipoatrophy in patients with HIV lipodystrophy.
Who was studied?
28 HIV-infected patients and hyperinsulinemia and lipoatrophy who were receiving antiviral medications.
How was the study done?
All patients underwent initial testing of their blood levels of fat, sugar, insulin, and other chemicals involved in metabolizing these substances. The amount of fat in the legs and belly was measured by performing computed tomography (which can accurately measure the amount and location of fat). Patients were then randomly assigned to receive either rosiglitazone or placebo. Neither the patients nor the doctors knew which pill patients were being given. After 3 months of treatment, the tests were repeated.
What did the researchers find?
Both the rosiglitazone group and the placebo group started out with the same severity of abnormalities of sugar metabolism and fat distribution. Rosiglitazone treatment statistically significantly improved the way sugar was metabolized by the body and decreased hyperinsulinemia. Similarly, rosiglitazone improved fat metabolism and increased fat deposition in the legs when compared with patients who received placebo. No statistically significant differences were found in belly fat between the 2 groups after treatment.
What were the limitations of the study?
The small size and short duration of the study prevent firm conclusions about the clinical usefulness of rosiglitazone in patients with HIV lipodystrophy. In addition, the study did not determine whether rosiglitazone decreases the risk for heart attacks and strokes.
What are the implications of the study?
Rosiglitazone may help block some of the adverse effects of antiretroviral therapy in patients with HIV infection.
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  J. Fuller A 39-Year-Old Man With HIV-Associated Lipodystrophy JAMA, September 3, 2008; 300(9): 1056 - 1066. [Abstract] [Full Text] [PDF]
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J. Lo, S. M. You, B. Canavan, J. Liebau, G. Beltrani, P. Koutkia, L. Hemphill, H. Lee, and S. Grinspoon Low-Dose Physiological Growth Hormone in Patients With HIV and Abdominal Fat Accumulation: A Randomized Controlled Trial JAMA, August 6, 2008; 300(5): 509 - 519. [Abstract] [Full Text] [PDF]
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 T. T. Brown Approach to the Human Immunodeficiency Virus-Infected Patient with Lipodystrophy J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 2937 - 2945. [Abstract] [Full Text] [PDF]
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 S. K. Grinspoon, C. Grunfeld, D. P. Kotler, J. S. Currier, J. D. Lundgren, M. P. Dube, S. E. Lipshultz, P. Y. Hsue, K. Squires, M. Schambelan, et al. State of the Science Conference: Initiative to Decrease Cardiovascular Risk and Increase Quality of Care for Patients Living With HIV/AIDS: Executive Summary Circulation, July 8, 2008; 118(2): 198 - 210. [Full Text] [PDF]
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 L. Mandel and D. Alfi Drug-induced paraparotid fat deposition in patients with HIV: Case reports J Am Dent Assoc, February 1, 2008; 139(2): 152 - 157. [Abstract] [Full Text] [PDF]
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 K. Samaras Metabolic consequences and therapeutic options in highly active antiretroviral therapy in human immunodeficiency virus-1 infection J. Antimicrob. Chemother., February 1, 2008; 61(2): 238 - 245. [Abstract] [Full Text] [PDF]
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 J. Falutz, S. Allas, K. Blot, D. Potvin, D. Kotler, M. Somero, D. Berger, S. Brown, G. Richmond, J. Fessel, et al. Metabolic Effects of a Growth Hormone-Releasing Factor in Patients with HIV N. Engl. J. Med., December 6, 2007; 357(23): 2359 - 2370. [Abstract] [Full Text] [PDF]
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 S. Gavi, J. J. Feiner, M. M. Melendez, D. C. Mynarcik, M. C. Gelato, and M. A. McNurlan Limb Fat to Trunk Fat Ratio in Elderly Persons Is a Strong Determinant of Insulin Resistance and Adiponectin Levels J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2007; 62(9): 997 - 1001. [Abstract] [Full Text] [PDF]
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C. G. Morse and J. A. Kovacs Metabolic and skeletal complications of HIV infection: the price of success. JAMA, August 16, 2006; 296(7): 844 - 854. [Abstract] [Full Text] [PDF]
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J. H. Lee, J. L. Chan, E. Sourlas, V. Raptopoulos, and C. S. Mantzoros Recombinant Methionyl Human Leptin Therapy in Replacement Doses Improves Insulin Resistance and Metabolic Profile in Patients with Lipoatrophy and Metabolic Syndrome Induced by the Highly Active Antiretroviral Therapy J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2605 - 2611. [Abstract] [Full Text] [PDF]
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 Z. T. Bloomgarden Aspects of type 2 diabetes and related insulin-resistant States. Diabetes Care, March 1, 2006; 29(3): 732 - 740. [Full Text] [PDF]
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 J. P.H. van Wijk, E. J.P. de Koning, M. C. Cabezas, J. op't Roodt, J. Joven, T. J. Rabelink, and A. I. Hoepelman Comparison of Rosiglitazone and Metformin for Treating HIV Lipodystrophy: A Randomized Trial Ann Intern Med, September 6, 2005; 143(5): 337 - 346. [Abstract] [Full Text] [PDF]
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M. Oette, M. Kurowski, T. Feldt, A. Kroidl, A. Sagir, C. Vogt, M. Wettstein, and D. Haussinger Impact of rosiglitazone treatment on the bioavailability of antiretroviral compounds in HIV-positive patients J. Antimicrob. Chemother., August 1, 2005; 56(2): 416 - 419. [Abstract] [Full Text] [PDF]
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D. Kamin, C. Hadigan, M. Lehrke, S. Mazza, M. A. Lazar, and S. Grinspoon Resistin Levels in Human Immunodeficiency Virus-Infected Patients with Lipoatrophy Decrease in Response to Rosiglitazone J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3423 - 3426. [Abstract] [Full Text] [PDF]
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A. Martin and P. W. G. Mallon Therapeutic approaches to combating lipoatrophy: do they work? J. Antimicrob. Chemother., May 1, 2005; 55(5): 612 - 615. [Abstract] [Full Text] [PDF]
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S. Grinspoon and A. Carr Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults N. Engl. J. Med., January 6, 2005; 352(1): 48 - 62. [Full Text] [PDF]
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N. Mikhail Rosiglitazone for Treatment of HIV Lipodystrophy Ann Intern Med, November 2, 2004; 141(9): 739 - 739. [Full Text] [PDF]
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 Other articles noted Evid. Based Med., September 1, 2004; 9(5): e5 - e5. [Full Text] [PDF]
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P. Koutkia, B. Canavan, J. Breu, M. Torriani, J. Kissko, and S. Grinspoon Growth Hormone-Releasing Hormone in HIV-Infected Men With Lipodystrophy: A Randomized Controlled Trial JAMA, July 14, 2004; 292(2): 210 - 218. [Abstract] [Full Text] [PDF]
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