Pravastatin restores fat during protease inhibitor treatment

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The lipid-lowering drug pravastatin produced significant gains in limb fat in HIV-positive people who received the drug during a small 12 week study, suggesting that the drug may have benefits for people suffering from fat loss (lipoatrophy) associated with antiretroviral treatment. The findings were presented today at the Seventh International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, in Dublin, Ireland.

However the study was not primarily designed to detect changes in limb fat, and did not record what proportion of patients had lipoatrophy at the outset of the study. Nor is the mechanism by which pravastatin might restore limb fat understood. Presenting the results, Dr Patrick Mallon of the National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Australia, said that a larger randomised study was needed in order to investigate the discovery more thoroughly.

Pravastatin was being tested in this study for its lipid-lowering effect, and is the preferred drug from the statin class used as lipid-lowering treatment, due to its minimal interaction with ritonavir and other protease inhibitors.

Glossary

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

lipid

Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

lipoatrophy

Loss of body fat from specific areas of the body, especially from the face, arms, legs, and buttocks.

The study randomised 16 patiens to receive pravastatin and 17 to receive a placebo. All participants were receiving treatment with a protease inhibitor, all but two boosted by ritonavir. Only two patients were taking thymidine analogues (AZT or d4T), which have been strongly associated with the development and progression of lipoatrophy.

At baseline totral cholesterol measured 7.6mmol/L in both groups. Patients were well matched in terms of CD4 cell counts and time on HIV therapy, although the pravastatin group had a higher median age (52 years vs 43 years).

The study enrolled patients into a four week observation period during which participants were asked to make dietary adjustments after consultation with a dietitian. Treatment started at week 4 and continued for twelve weeks.

At week 16 of the study total cholesterol had fallen by 0.6mmol/L in the pravastatin group, compared to a fall of 0.4mmol/L in the placebo group, a non-significant difference (p=0.8). However there was a significant difference in total cholesterol decline between weeks 4 and 16, which was a secondary endpoint of the study (-0.82mmol/L vs -0.34mmol/L, p=0.04), and non-HDL cholesterol fell by –1.02mmol/L in the pravastatin group compared to -0.4mmol/L in the placebo group (p=0.01).

There was no significant difference between the two groups in blood pressure, homocysteine, C-reactive protein, fibrinogen or flow-mediated vasodilation at baseline or week 16.

Fat changes

The study also carried out baseline and week 16 measurements of body fat distribution, using DEXA scan and CAT scans. At baseline total body fat was 15.9kg in the pravastatin group and 17kg in the placebo group. After 16 weeks the pravastatin group had gained 1.03kg of body fat, compared to a 0.090kg reduction in the placebo group (p=0.01). Limb fat increased by 0.72kg in the pravastatin group, compared to an increase of 0.19kg in the placebo group (p=0.04).

No switches in antiretroviral treatment took place during the study, and all participants maintained undetectable viral load.

This degree of limb fat gain after 12 weeks of pravastatin treatment is comparable or better than the the fat gain seen 48 weeks after switching from AZT or d4T to abacavir or tenofovir.

Limb fat is a better measure of subcutaneous fat gain than total body fat because total body fat can include visceral/abdominal fat, which produces the distended belly seen in some people with lipodystrophy.

References

Mallon PWG et al. Changes in body composition and cardiovascular measures in hypercholesterolaemic HIV-infected men treated with pravastatin: a randomized, placebo-controlled study. Antiviral Therapy 10: L5, 2005.