Metabolic Effects of Rosiglitazone in HIV Lipodystrophy

A Randomized, Controlled Trial

  1. Colleen Hadigan, MD, MPH;
  2. Sigal Yawetz, MD;
  3. Abraham Thomas, MD;
  4. Fiona Havers, MA;
  5. Paul E. Sax, MD; and
  6. Steven Grinspoon, MD
  1. From Massachusetts General Hospital and Brigham and Women's Hospital, Boston, Massachusetts.

    Abstract

    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-γ signaling.

    Objective: To investigate the effects of rosiglitazone (4 mg/d), a peroxisome proliferator–activated receptor-γ 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-γ 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.

    Article and Author Information

    • 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.

    Responses to this article

    • Rosiglitazone for treatment of HIV lipodystrophy
      • Nasser Mikhail
      Ann Intern Med published online October 26, 2009
    • In Response:
      • Colleen Hadigan and
      • Steven Grinspoon, MD
      Ann Intern Med published online October 26, 2009

    Summary for Patients

    • Summaries for Patients:Rosiglitazone Treatment for Fat Redistribution and Metabolic Abnormalities Caused by Anti-HIV Therapy Ann Intern Med May 18, 2004 140:I-36
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    1. Ann Intern Med May 18, 2004 vol. 140 no. 10 786-794
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