Pravastatin increases limb fat in HIV-positive patients with hypercholesterolaemia
Simon Collins, HIV i-Base
Paddy Mallon and colleagues from University of New South Wales always produce important studies at the Workshop. This year was no exception, with a study looking at changes in body composition in patients with elevated cholesterol who were treated with 40mg/day of pravastatin. Although pravastatin is often used in HIV-positive patients to reduce cholesterol, and is preferred over other statins due to fewer drug interactions with ARVs, this was the first study to look at whether it has an impact on body composition.
Thirty-three HIV-positive men on stable PI-containing HAART who had fasted cholesterol > 6.5 mmol/l were given dietary advice and started on a lipid-lowering diet for four weeks. They were then randomised to receive either pravastatin or placebo from week 4 to week 16. The primary endpoint of the study was time adjusted change in total cholesterol from baseline, with secondary endpoints looking at change in cholesterol from week 4, body composition using DEXA and abdominal CT, and additional lipid and cardiovascular risk markers.
Results are summarised in Table 1 below.
Table 1: Changes in cholesterol and body fat in patients treated with pravastatin or placebo
|Chol AUC 0-16 week (mmol/l-1/wk)||– 0.6||-0.4||0.8|
|Chol AUC 4-16 week (mmol/l-1/wk)||– 0.82||-0.34||0.04|
|Total fat (kg)||+ 1.03||-0.09||0.01|
|Limb fat (kg)||+ 0.72||+0.19||0.04|
|% IAF||– 2.90||0.08||0.70|
Although the decreases in cholesterol were modest, with the difference between the pravastatin and placebo group only becoming significant from week 4 to 16 (a secondary endpoint of the study), body fat increased significantly in the pravastatin group, and this was predominantly driven by an increase in limb fat.
Homocysteine was the only cardiovascular risk marker to be reduced during the study (in the pravastatin group) with no significant differences occurring in other cardiovascular, lipid, glucose or dietary parameters.
Statins in general, and pravastatin in particular, have other pharmacological actions in the body other than lipid lowering, which may impact favourably on lipoatrophy.
Pravastatin has been shown to have protective role against the development of diabetes in one large clinical trial. Moreover, a recent clinical study revealed that pravastatin treatment improved insulin sensitivity in 25 women with the metabolic syndrome who had impaired glucose intolerance.
Additionally, statins are immunologically active and also act as anti-inflammatories. These pathways may also be involved in their beneficial action on lipoatrophy.
Mallon PWG, Miller J, Carr A et al. Changes in body composition and cardiovascular measures in hypercholesterolaemic HIV-infected men treated with pravastatin: a randomised, placebo-controlled study. 7th Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 13-16 November 2005, Dublin. Abstract 23.