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6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV25–28 October 2004 - Washington, DC, USA |
ENDOTHELIAL DYSFUNCTION IN HIV-INFECTED PATIENTS ON CART DOES NOT IMPROVE EVEN WHEN LIPID PROFILES IMPROVE ON PRAVASTATIN
Antiviral Therapy 2004; 9(6):L15 (abstract no. 24)
PA Sklar1,2, JR Grubb2, JD Voell3, G Zalos4, WC Blackwelder2, JA Metcalf3, A Rupert5, MT Gladwin2, J Witek1, RT Davey3, H Masur2 and RO Cannon4
1Drexel University, Philadelphia, Pa., USA; 2Clinical Center, NIH, Bethesda, Md., USA; 3NIAID, NIH, Bethesda, Md., USA; 4NHLBI, NIH, Bethesda, Md., USA; and 5Science Application International Corporation, Frederick, Md., USA
BACKGROUND: Atherogenic dyslipidaemia is common among HIV+ individuals on CART and there is evidence that this may translate into premature cardiovascular (CV) disease. An empiric approach has been to modify lipids and thus decrease CV risk through the use of HMG Co-A reductase inhibitors.
METHODS: 23 HIV+ patients on stable CART completed a randomized, placebo-controlled, crossover study to evaluate the effect of pravastatin (40 mg) on endothelial function. Endothelial function (EF) – central to vascular pathophysiology – was assessed by flow-mediated vasodilation (FMD) of the brachial artery.
RESULTS: At baseline, HIV+ individuals demonstrated abnormal EF compared with an otherwise healthy HIV-population (mean ±SEM, 7.0 ±0.5% HIV vs 10.1 ±0.9 controls, P=0.002). As expected, active treatment with pravastatin significantly improved total-C (mean difference ±SEM, –36 ±5 mg/dl, P<0.001), LDL-C (–30 ±4, P<0.001) and triglycerides (–69 ±25, P=0.01); but not HDL-C or measures of insulin resistance. Despite the overall improvement in metabolic risk profiles, pravastatin yielded no consistent or significant improvement in EF (mean difference in FMD ±SEM between drug and placebo, –0.3 ±0.8%, P=0.68; means 7.0% on drug, 7.3% on placebo). Furthermore, pravastatin did not yield a significant decline in C-reactive protein (CRP) values (mean difference ±SEM, –0.4 ±1.9 mg/l, P=0.85; means 6.3 on drug, 6.7 on placebo); there was no significant correlation between FMD and CRP at baseline (correlation coefficient = –0.16, P=0.45)
CONCLUSIONS: While pravastatin improves the dyslipidaemia of HIV+ individuals on CART this does not translate into improved EF. Persistently elevated CRP values suggest that there may be an ongoing stimulus towards CV risk which has yet to be elucidated.
2004-10-25
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