Statins and fibrates, the two classes of drugs used to treat abnormally high blood fats, are equally safe and effective in HIV-positive patients treated with protease inhibitors who have hyperlipidaemia, according to Italian research published in the April 2003 edition of AIDS.
Fibrates have been propsed as an alternative to statins due to the potential for interactions between protease inhibitors and statins, both of which are metabolised by the cytochrome p450 system.
Investigators at the University of Bologna conducted a prospective, randomised, open label study involving 106 patients with abnormally high lipid levels in plasma and body fat redistribution, who had received HAART involving a protease inhibitor for at least a year.
An abnormally high level of triglycerides was defined as a fasting plasma level of above 300mg/dl, and hypercholesterolemia was diagnosed when fasting total cholesterol levels in plasma were 290mg/dl or above.
Body fat redistribution was diagnosed on physical examination and included either peripheral fat wasting or fat accumulation.
All the patients enrolled to the study had a viral load below 50 copies/ml and abnormal blood fat levels for at least six months which had not improved with either changes in diet or exercise after three months.
Patients were randomised to receive bezafibrate (400mg once daily), gemfibrozil (600mg twice a day), fenofibrate (200mg once a day), pravastatin (20mg once a day) or fluvastatin (20 mg daily). Follow-up was for twelve months involving three-monthly visits to the clinic when plasma levels of HDL and LDL cholesterol, triglycerides, CD4 cell count, HIV viral load, liver and kidney and other tests were performed.
Investigators were primarily interested to see what effect statins and fibrates had on cholesterol and triglyceride levels compared to baseline and to see if treatment with lipid lowering drugs has an effect on CD4 count or viral load or caused any side-effects.
Abnormally high triglycerides were present in a little under 44% of patients at baseline and high cholesterol in 22.4%. Body fat redistribution was present in 30% of patients with high triglycerides and 15.5% of patients with abnormal cholesterol.
Triglyceride levels were significantly higher in patients treated with ritonavir compared to other protease inhibitors, but high cholesterol levels were not particularly associated with any particular protease inhibitor.
After one year of follow-up, it was found that fibrate treatment resulted in a 40.7% fall in baseline triglyceride levels and a 21.9% reduction in cholesterol levels. Slightly under two thirds of patients treated with fibrates achieved normal triglyceride and cholesterol levels. Neither the prevalence or severity of body fat changes altered in the fibrate-treated patients. All but one patient maintained a viral load below 50 copies/ml, and CD4 cell count increased by an average of 82 cells/mm3. The only significant side-effect reported was mild stomach upset, in a little under 9% of patients.
Statins reduced baseline triglyceride levels by 34.8% with cholesterol falling by a little over 25% from baseline. Normal triglyceride levels were achieved by 59.5% of patients and normal cholesterol by 60%. As with fibrates, there was no evidence of changes in the prevalence or severity of body fat changes in patients. Once again, the only side-effect seen was mild stomach upset, in 5.4% of patients. The viral load in all statin treated patients remained under 50 copies/ml whilst the average CD4 cell count increase was 98 cells/mm3.
Adherence to both fibrates and statins was 90%.
The investigators conclude: “In our study, pharmacological therapy with fibrates or statins proved effective in the management of diet-resistant dyslipidaemia in PI-treated HIV-infected patients”, adding that all the drugs used in the study “led to a remarkable reduction in plasma triglyceride and cholesterol levels”.
Fibrates proved particularly effective against triglycerides, whilst statins showed a more marked effect on cholesterol. However, no statistically significant differences of therapeutic response were observed according to class of lipid lowering drug used or between individual drugs. What’s more, both fibrates and statins were seen to be safe, having no adverse effect on either HIV viral load or CD4 cell count. Nor did either class of drugs cause significant side-effects.
Further information on this website
Cholesterol - Factsheet
Body fat changes on HAART (lipodystrophy) - Overview
Lipodystrophy - Factsheet
Claza L et al. Statins and fibrates for the treatment of hyperlipidaemia in HIV-infected patients receiving HAART. AIDS 17: 851-859, 2003.