[21] Improved triglycerides and insulin sensitivity with 3 months of acipimox in HIV-infected patients with hypertriglyceridemia

8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV

San Francisco, California - September 24 - 26, 2006

IMPROVED TRIGLYCERIDES AND INSULIN SENSITIVITY WITH 3 MONTHS OF ACIPIMOX IN HIV-INFECTED PATIENTS WITH HYPERTRIGLYCERIDEMIA

Antiviral Therapy 2006; 11:L14 (abstract no. 21)

C Hadigan¹, J Liebau¹, M Torriani², R Andersen¹ and S Grinspoon¹
¹Program in Nutritional Metabolism; ²Division of Musculoskeletal Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

CONTEXT: Treatment of hyperlipidemia, in particular hypertriglyceridemia, remains a challenge for optimizing long-term health of many HIV-infected patients on antiretroviral therapy.

OBJECTIVE: Elevation of free fatty acids (FFA) may contribute to hyperlipidemia and insulin resistance in HIVinfected patients. Therefore we evaluated the efficacy and safety of chronic inhibition of lipolysis in HIV-infected men and women with hypertrigyceridemia. We hypothesized that 3 months of acipimox would lead to significant sustained reductions in triglyceride levels and improvement in insulin sensitivity compared to placebo.

DESIGN: Three month, randomized, double-blind, controlled trial of acipimox (250 mg thrice daily) versus placebo, was conducted in 23 HIV infected men and women with hypertriglyceridemia (>150 mg/dl), abnormal fat distribution, and no current lipid lowering therapy. The primary outcome variable was improvement in triglyceride concentration. Insulin sensitivity measured by hyperinsulinemic euglycaemic clamp and rates of lipolysis determined using stable isotope tracers were secondary outcomes of interest.

SETTING: Academic medical center.

RESULTS: Acipimox resulted in significant sustained reductions in FFA (mean change -0.38 [0.06] versus 0.08 [0.06] mEq/l with placebo, P<0.0001), decreased rates of lipolysis (P<0.0001), and a 34 mg/dl mean reduction in triglyceride concentration at 3 months (MANOVA compared to placebo, P=0.01). In addition, acipimox administration was associated with improved insulin sensitivity in hyperinsulinemic euglycaemic clamp testing (mean change in M [mg glucose/kg lean body mass/min] acipimox +2.31 [0.74] versus placebo -0.21 [0.90], P=0.04). Improvements in glucose disposal were significantly correlated with reductions in FFA (r=-0.68, P=0.0007) and lipolysis (r=-0.62, P=0.003). There was also a trend towards decreased intramyocellular lipid content after acipimox administration (P=0.06).

CONCLUSIONS: Acipimox administration resulted in significant improvements in triglycerides, sustained reductions in lipolysis and improved glucose homeostasis in HIV infected individuals with hypertriglyceridemia. The improvement in overall metabolic profile with acipimox indicates an important potential clinical utility for this agent that requires further investigation.

Download PDF of this abstract.

2006-09-24
21

Copyright © 2006 - International Medical Press Ltd. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Medical Editor, International Medical Press, 36 St Mary-at-Hill, London EC3R 8DU, United Kingdom.