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ARTICLE

Metabolic Effects of Rosiglitazone in HIV Lipodystrophy

A Randomized, Controlled Trial

Colleen Hadigan, MD, MPH; Sigal Yawetz, MD; Abraham Thomas, MD; Fiona Havers, MA; Paul E. Sax, MD; and Steven Grinspoon, MD

18 May 2004 | Volume 140 Issue 10 | Pages 786-794

Background: Patients with HIV infection who are treated with antiretroviral agents often lose subcutaneous fat and have metabolic abnormalities, including insulin resistance and reduced adiponectin levels, which may be related to disrupted subcutaneous adipogenesis and altered peroxisome proliferator–activated receptor- signaling.

Objective: To investigate the effects of rosiglitazone (4 mg/d), a peroxisome proliferator–activated receptor- agonist, in HIV-infected men and women with hyperinsulinemia and lipoatrophy.

Design: A randomized, double-blind, placebo-controlled, 3-month study.

Setting: University hospital.

Patients: 28 HIV-infected men and women with hyperinsulinemia and lipoatrophy.

Measurements: Insulin sensitivity measured by euglycemic hyperinsulinemic clamp testing; subcutaneous leg fat area measured by computed tomography; adiponectin, free fatty acid, and lipid levels; and safety variables.

Results: Rosiglitazone, when compared with placebo, improved insulin sensitivity (mean [±SD] change, 1.5 ± 2.1 mg of glucose/kg of lean body mass per minute vs. –0.4 ± 1.6 mg/kg per minute; P = 0.02), increased adiponectin levels (mean [±SD], 2.2 ± 2.2 µg/mL vs. 0.1 ± 1.1 µg/mL; P = 0.006), and reduced free fatty acid levels (mean [±SD], –0.09 ± 0.1 mmol/L vs. 0.01 ± 0.1 mmol/L; P = 0.02). Mean percentage (±SD) of body fat (1.38% ± 3.03% vs. –0.83% ± 2.76%; P = 0.03) and subcubaneous leg fat area (2.3 ± 8.4 cm² vs. –0.9 ± 1.9 cm²; P = 0.02) increased significantly with rosiglitazone compared with placebo. Mean total cholesterol levels (±SD) also increased with rosiglitazone compared with placebo (0.6 ± 1.0 mmol/L [25 ± 37 mg/dL] vs. –0.4 ± 0.6 mmol/L [–15 ± 25 mg/dL]; P = 0.007).

Limitations: The study was relatively small and of short duration.

Conclusions: The authors demonstrated positive effects of rosiglitazone on lipoatrophy; insulin sensitivity; and metabolic indices, including adiponectin levels, in HIV-infected patients with lipoatrophy and insulin resistance. Peroxisome proliferator–activated receptor- agonists may correct the metabolic abnormalities associated with disrupted adipogenesis in this population. Further studies must determine the clinical utility of such agents in HIV-infected patients.

Editors' Notes Context Antiretroviral therapy often causes metabolic abnormalities characterized by lipoatrophy and HIV lipodystrophy. Thiazolidinediones (such as rosiglitazone) are peroxisome proliferator–activated receptor- agonists that improve insulin sensitivity and stimulate adipogenesis. Contribution In a randomized, double-blind, placebo-controlled study of HIV-infected individuals, rosiglitazone improved insulin sensitivity, increased adiponectin levels, decreased free fatty acid levels, and improved peripheral fat deposition during 3 months of treatment with antiretroviral agents. Implications Rosiglitazone seems to reverse some of the metabolic abnormalities that accompany antiretroviral therapy and may help prevent or moderate HIV lipodystrophy. Cautions The small sample size and short duration of treatment limit the generalizability of the findings. –The Editors

 

Author and Article Information

From Massachusetts General Hospital and Brigham and Women's Hospital, Boston, Massachusetts.

Acknowledgments: The investigators thank the nursing and bionutrition staffs at the Massachusetts Institute of Technology and Brigham and Women's General Clinical Research Center for their dedicated patient care and David Schoenfeld, PhD, and Hang Lee, PhD, for their statistical expertise in preparing this manuscript.

Grant Support: By National Institutes of Health grants RO1 DK 59535, K23 DK 02844, M01-RR300088, and M01-RR02635. Dr. Grinspoon has received unrestricted educational grant support from GlaxoSmithKline, and Dr. Sax has received research grant support and speaker's honoraria from GlaxoSmithKline.

Potential Financial Conflicts of Interest:Honoraria: P.E. Sax (GlaxoSmithKline); Grant received: P.E. Sax (GlaxoSmithKline), S. Grinspoon (GlaxoSmithKline).

Requests for Single Reprints: Colleen Hadigan, MD, MPH, Program of Nutritional Metabolism, Massachusetts General Hospital, 55 Fruit Street LON207, Boston, MA 02114; e-mail, chadigan{at}partners.org.

Current Author Addresses: Drs. Hadigan and Grinspoon and Ms. Havers: Program in Nutritional Metabolism, Massachusetts General Hospital, 55 Fruit Street LON207, Boston, MA 02114.

Drs. Yawetz and Sax: Division of Infectious Disease, Brigham and Women's Hospital, 75 Francis Street, PBB-A-4, Boston, MA 02115.

Dr. Thomas: Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, RFB-2, Boston, MA 02115.

Author Contributions: Conception and design: C. Hadigan, S. Yawetz, A. Thomas, S. Grinspoon.

Analysis and interpretation of the data: C. Hadigan, A. Thomas, F. Havers, P.E. Sax, S. Grinspoon.

Drafting of the article: C. Hadigan, F. Havers, P.E. Sax, S. Grinspoon.

Critical revision of the article for important intellectual content: C. Hadigan, A. Thomas, P.E. Sax, S. Grinspoon.

Final approval of the article: C. Hadigan, P.E. Sax, S. Grinspoon.

Provision of study materials or patients: P.E. Sax.

Statistical expertise: C. Hadigan.

Obtaining of funding: C. Hadigan, S. Grinspoon.

Administrative, technical, or logistic support: A. Thomas.

Collection and assembly of data: C. Hadigan, S. Yawetz, F. Havers.

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Summaries for Patients
Rosiglitazone Treatment for Fat Redistribution and Metabolic Abnormalities Caused by Anti-HIV Therapy

Annals 2004 140: I-36. [Full Text]  

Letters
Rosiglitazone for Treatment of HIV Lipodystrophy
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Annals 2004 141: 739. [Full Text]  

Letters
Rosiglitazone for Treatment of HIV Lipodystrophy
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