4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 22-25 September 2002, San Diego, CA, USA

EFFECTS OF PRAVASTATIN ON LIPIDS AND LIPOPROTEIN SUB-FRACTIONS IN PATIENTS RECEIVING HIV PROTEASE INHIBITORS

Antiviral Therapy 2002; 7:L34 (abstract 50)

JH Stein, MA Merwood, JL Bellehumeur and JM Sosman
University of Wisconsin Medical School, Madison, Wis., USA

BACKGROUND: Pravastatin is used frequently to treat HIV-infected patients with protease inhibitor (PI)- associated dyslipidemia, however its effectiveness at treating this disorder has not been established in a placebo-controlled trial. Furthermore, the effects of pravastatin on atherogenic lipoproteins and their subfractions have not been determined in patients taking PIs.

OBJECTIVE: To determine the effects of pravastatin on lipids and lipoprotein subfractions in patients with PI-associated dyslipidemia.

METHODS: In a placebo-controlled single-blind crossover trial, HIV-positive subjects on a stable antiretroviral regimen including a PI received 8 weeks of therapy with diet and placebo, followed by 8 weeks of therapy with diet and pravastatin, 40 mg nightly. Serum samples were obtained after a 12 h fast. Lipid mass concentrations of 16 lipoprotein fractions, average particle sizes, and particle concentrations were quantified by nuclear magnetic resonance spectroscopic lipoprotein subclass analysis (LipoScience, Inc., Raleigh, NC, USA).

RESULTS: Baseline lipid values (mean ±SEM) from the 16 subjects (44 ±2 years old) were: total cholesterol 224 ±17, LDL-C 140 ±14, HDL-C 36 ±3, triglycerides 350 ±68, non-HDL-C 188±16 mg/dl. At baseline, the LDL particle concentration was high (1882 ±205 nmol/l), LDL particles were small (pattern B, 19.7 ±0.2 nm), the large HDL concentration was low (10.7 ±1.7 mg/dl), and the large VLDL concentration was high (167 ±59 mg/dl), all of which are associated with increased coronary heart disease risk. Compared with placebo, pravastatin significantly reduced the concentration of LDL particles (on-treatment, 1512 ±147 nmol/l, P=0.005) and small VLDL particles (P=0.016). The concentration of large VLDL particles did not change significantly (-10 ±60, P=0.444). Large (P=0.078) and small (P=0.098) LDL particles tended to decrease similarly, so the average LDL particle size did not change (P=0.225). Corresponding lipid concentrations that also improved include total cholesterol (-42 ±9 mg/dl, P<0.001), LDL-C (-29 ±9 mg/dl, P=0.001), triglycerides (-59 ±62 mg/dl, P=0.068), and non-HDLC (-42 ±8 mg/dl, P<0.001).

CONCLUSIONS: Use of pravastatin reduced concentrations of LDL and small VLDL particles, changes that are associated with decreased coronary heart disease risk in non-HIV-infected populations. Particle sizes and concentrations of other atherogenic lipoproteins did not improve, indicating that combinations of lipid-lowering therapies may be needed to normalize the lipoprotein abnormalities observed in patients taking PIs.

Presenting author: JM Sosman

2002-09-22
50

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