Background:<b/>  The use of PI in HIV has been associated with dyslipidemia and vascular endothelial dysfunction, which may predispose patients to atherosclerosis. Although pravastatin is recommended as initial therapy for dyslipidemic patients taking PI, pravastatin's effects on lipoproteins and  vascular endothelial function have not been elucidated. The purpose of this study was to determine the effects of pravastatin on lipoprotein subfractions and endothelial function in dyslipidemic patients receiving PI.

Methods:  This was a placebo-controlled, double-blind, crossover study comparing pravastatin (40 mg) to placebo in 20 non-diabetic, HIV⁺ individuals taking ART containing PI. Lipoprotein subfractions were measured by nuclear magnetic resonance spectroscopy. Arterial endothelial function was measured via flow-mediated vasodilation (FMD) of the brachial artery  using high-resolution ultrasound.

Results:  At baseline, subjects had (mean ± standard error):  hypercholesterolemia (total cholesterol 216 ± 15 mg/dL), hypertriglyceridemia (335 ± 59 mg/dL), and low high-density lipoprotein cholesterol (HDL-C, 36 ± 3 mg/dL) with increased non-HDL-C levels (180 ± 14 mg/dL). Subjects had increased concentrations of low-density lipoprotein (LDL) particles (1756 ± 180 nmol/L), which were small (19.9 ± 0.2 nm), low concentrations of large HDL (12 ± 2 mg/dL), and high concentrations of large very low-density lipoproteins (VLDL) (168 ± 51 mg/dL). FMD was impaired (4.5 ± 1.1%), indicating endothelial dysfunction. Compared with placebo, pravastatin reduced total cholesterol by 18% (p <0.001), LDL-C by 20% (p = 0.022), and non-HDL-C by 22% (p <0.001). Pravastatin therapy was associated with reduction in LDL (-21%, p = 0.030), small LDL (-27%, p = 0.100), and small VLDL (-45%, p = 0.023), and improved FMD (0.7 ± 0.6%, p = 0.080). Predictors of improved FMD with pravastatin included glucose (p = 0.004), intermediate-density lipoprotein (p = 0.001), and HDL-C (p = 0.042) levels (r² adjusted = 66.4%, p <0.001).

Conclusions:  This is the first double-blind, placebo-controlled study of the effects of statin therapy on lipoprotein subfractions and endothelial function in individuals taking HIV PIs. Pravastatin therapy was associated with improved endothelial function and lower concentrations of atherogenic lipoproteins, particularly those most associated with future coronary events.

Keywords: cardiovascular risk; endothelial function; statin therapy