5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 8–11 July 2003, Le Meridien Montparnasse, Paris, France

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ROSIGLITAZONE FOR PATIENTS WITH HIV LIPODYSTROPHY

Antiviral Therapy 2003; 8:L12 (abstract 12)

C Hadigan¹, S Yawetz², A Thomas³, F Havers¹, PE Sax² and S Grinspoon^1
1Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA; ²Infectious Diseases Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; and ³Endocrine Division, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA

Patients treated with antiretroviral therapy often demonstrate loss of subcutaneous fat and metabolic abnormalities, including insulin resistance. We investigated the effects of rosiglitazone on insulin sensitivity, subcutaneous fat and metabolic indices in patients with HIV lipodystrophy. We conducted a 3-month randomized double-blind placebo-controlled study of rosiglitazone (4 mg/day) in 28 HIV-infected subjects ages 18–60 years with hyperinsulinaemia and lipoatrophy. Insulin sensitivity was assessed by euglycaemic, hyperinsulinaemic clamp and metabolic indices included adiponectin and lipid profile. Body composition assessment included percent body fat and subcutaneous adipose tissue (SAT) area by computerized tomography (CT) scan of the abdomen. After 3 months, subjects continued on open-label extension with a dose escalation to 8 mg/day for an additional 3 months. Rosiglitazone resulted in improved insulin sensitivity, with increased glucose utilization (+1.7 ±0.6 vs –0.4 ±0.5 mg glucose/kg lean body mass/minute, P<0.02, mean change ± standard error of measurement [SEM]), increased percent body fat (1.38 ±0.76 vs –0.91 ±0.87, P=0.04) and adiponectin (2.3 ±0.6 vs 0.1 ±0.3 µg/ml, P<0.01, rosiglitazone vs placebo, respectively). SAT increased 8% (P=0.01) with rosiglitazone, but <1% with placebo. Self-reported lipoatrophy improved significantly with rosiglitazone (P=0.03). Total cholesterol increased with rosiglitazone compared to placebo (mean change +25 ±9 vs –16 ±8 mg/dl, P<0.01). With open-label extension, insulin sensitivity remained improved and SAT increased further for a net change of +12% from baseline after 6 months. These data demonstrate positive effects of rosiglitazone on insulin sensitivity and fat in HIV-infected patients with lipodystrophy and insulin resistance. Thiazolidinediones may provide an important therapeutic benefit. Studies are needed to identify optimal dose, duration of treatment, subpopulations most likely to benefit and choice of specific thiazolidinedione to minimize effects on cholesterol.

Presenting author: C Hadigan

2003-07-08
12

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