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8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIVSan Francisco, California - September 24 - 26, 2006 |
EFFECTS OF ANTI-INFLAMMATORY THERAPY ON BODY COMPOSITION AND METABOLIC ALTERATIONS IN HIV LIPODYSTROPHY: A PILOT STUDY
Antiviral Therapy 2006; 11:L24 (abstract no. 34)
G Ionescu1, S Reka2, JB Albu1, ES Engelson1 and DP Kotler1
1St. Luke’s Roosevelt Hospital Center, New York, NY, USA; 2SUNYDownstate Medical Center, Brooklyn, NY, USA
BACKGROUND: Dysregulated inflammatory response may promote HIV lipodystrophy (HIVL). The effects of antiinflammatory therapy are unknown.
AIMS: We studied the in vivo effects of choline magnesium salicylate (trilisate) for 6 months on body fat distribution, on metabolism, and on systemic inflammation in a prospective, open-label pilot study. Subjects with HIVL were included. The primary endpoint was change in body fat distribution. Secondary endpoints were changes in glucose and lipid metabolism, and in serum cytokines.
METHODS: After baseline studies, trilisate was initiated at a dose of 1.5 g bid, adjusted monthly to maintain an antinflammatory salicylate concentration of 20 mg/dl, or 1.48 mM. Body composition was evaluated by DXA. Glucose disposal rate was determined during a low-dose euglycaemic hyperinsulinemic clamp. Fasting serum lipids and soluble TNF receptor concentrations were measured. Safety was ensured by monthly serum salicylate levels and liver and renal chemistries.
RESULTS: Seven subjects initiated the study; 4 males and 2 females completed it. None were taking zidovudine, stavudine, or antidiabetic drugs, while all took hypolipidemic therapy. Average salicylate concentration throughout the study was 11 mg/dl. Baseline mean DXA trunk/limb fat was 4.7 and did not change significantly following therapy. Fasting blood glucose decreased from 108 to 90 mg/dl at the end of the study (P<0.05). Fasting insulin increased non-significantly from 22.1 to 23.2 mU/ml without significant changes in glucose disposal rate, or fatty acid levels during the clamp. Serum lipids rose nonsignificantly. Mean baseline sTNFR 1 and 2 were increased, compared to historical controls, and did not change with therapy. One female subject experienced an asymptomatic, three-fold elevation in ALT and AST, with a therapeutic level of salicylate (20 mg/dl). Following a 25%-dose reduction, liver enzymes normalized.
DISCUSSION: Standard doses of trilisate are safe in HIVL, for a limited time. Therapy did not affect body composition, glucose disposal, or serum lipids. These results may be due to an inadequate salycilate level and subsequent lack of anti-inflammatory effect, as soluble TNF receptor levels did not change. However, fasting glucose concentration decreased significantly, which may be explained by decreased gluconeogenesis, a reported salicylate effect, rather than changes in insulin sensitivity.
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2006-09-24
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