Lipid-lowering drugs more effective than switch to NNRTI in managing lipid elevations

Lipid elevations that occur during protease inhibitor therapy may be more effectively managed by prescribing lipid-lowering drugs than by switching to nevirapine (Viramune) or efavirenz (Sustiva), according to results of a randomised study reported in the July 1st edition of the journal AIDS.

Lipid elevations in protease inhibitor-treated patients have been managed in a variety of ways. Although lipid-lowering drugs have been employed, interactions between protease inhibitors and statins, together with cost and extra pill burden, have made many doctors more sympathetic to switching to a PI-containing regimen if possible.

However, NNRTI-containing regimens are not without their own effects on lipids, the switch may result in a loss of virologic control, and the magnitude of the lipid reduction may not be great enough to substantially reduce the risk of cardiovascular events.

Accordingly, Italian researchers set out to compare different approaches. The study, conducted at the University of Bologna in Italy, randomised 132 patients with elevated lipid levels to switch from their protease inhibitor-containing regimen to nevirapine (n=29) or efavirenz (n=34), or to stay on their PI-containing regimen and add either pravastatin (Lipostat)(n=36) or bezafibrate (Bezalip)(n=31). Patients were followed for twelve months and the study was open label, so doctor and patient knew which arm they had been allocated to.

Patients were eligible to join the study if they were taking their first PI-containing regimen, had controlled viral load for at least six months and both hypertriglyceridemia (>200mg/dl) and hypercholesterolemia (>250mg/dl) that been unresponsive to diet and exercise over at least three months. Ongoing protease inhibitor therapy consisted of lopinavir/ritonavir (27.7%), nelfinavir (21%), indinavir (16%), indinavir/ritonavir (8.5%), saquinavir (13%), saquinavir/ritonavir (7%) and amprenavir/ritonavir (3%). Forty-six per cent of all patients were taking d4T (stavudine, Zenit), the only nucleoside analogue associated with lipid elevation.

There were no significant differences between the treatment groups in age, gender, baseline CD4 cell count or triglyceride and cholesterol levels. The mean baseline triglyceride level was 293mg/dl and the mean total cholesterol level was 266mg/dl, with triglyceride levels significantly higher among the lopinavir-treated group (358mg/dl) at baseline.

After 12 months a significant difference in lipid levels had emerged. Patients treated with lipid-lowering drugs experienced a 44% decrease in triglycerides, compared to a mean decrease of 18% in the NNRTI-treated group

(p

Triglyceride levels fell into the normal range in 50% of the group treated with lipid-lowering drugs compared to 19% of the NNRTI group (OR 4.4, p

Although the authors suggest that lipid-lowering therapy becomes suitable only when diet, exercise and treatment switching have been tried or dismissed as unsuitable, these findings are likely to open up debate about the management of lipid elevations in all patients given the magnitude of lipid reduction and normalisation achieved when compared with previous studies.