540   A Randomised, Double-Blind Study of Gemfibrozil (GF) for the Treatment of Protease Inhibitor-Associated Hypertriglyceridaemia.

J. Miller*¹, A. Carr², D. Brown¹, and D. A. Cooper².
¹Natl. Ctr. in HIV Epidemiology and Clin. Res., Univ. of New South Wales and²St. Vincent's Hosp., Sydney, NSW, Australia.

Background:A syndrome of lipodystrophy has been widely described in patients with HIV, especially those taking protease inhibitors (PIs). Hypertriglyceridaemia has been a predominant metabolic feature in these descriptions, frequently observed at levels associated with accelerated cardiac disease. Gemfibrozil is clinically indicated for the treatment of hypertriglyceridaemia.

Methods:To explore the safety and efficacy of a potential therapeutic intervention for patients with elevated triglycerides (TGs) we conducted a 16-week, randomised, double-blind, comparative study of low-saturated-fat diet alone versus low-saturated-fat diet with gemfibrozil (GF) 600 mg bid in patients with TGs >3 mmol/L and currently receiving PI therapy. Following a 4-week period of dietary intervention alone, patients were randomised to GF or matching placebo for 12 weeks. Efficacy measures included fasting lipids, free fatty acids, glucose, insulin and c-peptide.

Results:3 6 patients, all male, were randomised into the study (16 GF, 20 placebo). Median baseline TGs were 5.6 mmol/L, cholesterol 6.8 mmol/L, glucose 4.8 mmol/L and insulin 7.4 mU/L. Patients on GF had decreases in TGs over 12 weeks (-1.326 mmol/L) compared to placebo (+0.37 mmol/L) [p = 0.06]; however, only one patient had TGs return to normal range (<2.00 mmol/L). No significant changes in cholesterol, HDL cholesterol, free fatty acids, fasting glucose or insulin were observed. GF was well tolerated and did not appear to induce additional PI toxicity.

Conclusions:GF is safe and demonstrates modest efficacy for patients with PI-associated hypertriglyceridaemia. It appears unlikely that it will lower TGs sufficiently in this patient group, at least in the presence of continued PI use, to confer sufficient clinical benefit.