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7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV13–16 November 2005, Dublin, Ireland |
Changes in body composition and cardiovascular measures in hypercholesterolaemic HIV-infected men treated with pravastatin: a randomized, placebo-controlled study
PWG Mallon1,2, J Miller2, J Kovacic3, J Kent- Hughes2, R Norris2, K Samaras4, M Feneley3, DA Cooper1,2 and A Carr2
1National Centre in HIV Epidemiology and Clinical Research, University of New South Wales; 2HIV, Immunology and Infectious Diseases Clinical Services Unit, St Vincent’s Hospital; 3Department of Cardiology, St Vincent’s Hospital; 4Garvan Institute of Medical Research, Sydney, Australia
Antiviral Therapy 2005; Supplement 3:L15 (abstract no. 23)
OBJECTIVES: Protease inhibitor (PI) use is associated with hypercholesterolaemia, peripheral lipoatrophy and central fat accumulation. We aimed to determine the effect of the HMG-CoA reductase inhibitor pravastatin in HIV-infected, PI-treated men with hypercholesterolaemia.
METHODS: A randomized, placebo-controlled, 16-week study of pravastatin 40mg daily in 33 HIV-infected men on stable PI therapy (HIV RNA <400 copies/ml) with high fasting cholesterol (>6.5 mmol/l). Subjects commenced a lipid-lowering diet at week 0 and were randomized to pravastatin or placebo at week 4. Primary endpoint was time-weighted change (AUC) in total cholesterol from week 0. Secondary endpoints included AUC cholesterol from week 4 (start of pravastatin), body composition (DEXA and abdominal CT), high density lipoprotein cholesterol, triglycerides, glucose, insulin, endothelial function (flow mediated vasodilatation [FMV]) and markers of cardiovascular risk (homocysteine, hs-CRP, fibrinogen and PAI-1). Non-parametric analyses were used and results presented as median [IQR].
RESULTS: Of 33 men enrolled (pravastatin n=16), 31 completed the study. Groups were matched for baseline cholesterol (7.6 [1.7] pravastatin vs 7.6 [1.4] mmol/l placebo) and body composition, but the pravastatin group was older (52 [12] vs 43 [9] years) with greater endothelial dysfunction (%FMV 3.2 [3] vs 4.7 [3.4]). Although there was no significant difference in AUC cholesterol from week 0 between groups, AUC cholesterol from week 4 decreased more in the pravastatin group (Table 1). Total fat, predominantly limb fat, increased significantly in the pravastatin group. Apart from homocysteine, which decreased in the pravastatin group, there were no significant differences in other cardiovascular, lipid, glucose or dietary parameters.
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| Table 1. | |||
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| Change in parameter | Pravastatin | Placebo | P |
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| Cholesterol AUC | |||
| wk 0–16 (mmol.l–1/wk) | –0.6 [0.98] | –0.4 [0.98] | 0.8 |
| Cholesterol AUC | |||
| wk 4–16(mmol.l–1/wk) | –0.82 [0.97] | –0.34 [0.91] | 0.04 |
| Total fat (kg) (DEXA) | +1.03 [1.94] | –0.09 [1.35] | 0.01 |
| Limb fat (kg) (DEXA) | +0.72 [1.55] | +0.19 [0.48] | 0.04 |
| % intra-abdominal fat (CT) | –2.9 [10.9] | 0.08 [9.4] | 0.7 |
| Homocysteine (µmol/l) | –2.2 [3.1] | +0.5 [2.5] | 0.046 |
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CONCLUSIONS: Despite limited effects on cholesterol, use of pravastatin 40mg daily for 12 weeks in this population resulted in significant increases in limb fat.
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2005-11-13
23
Copyright © 2005 - 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.