HIV Digest	HIV Digest Archive

Managing the dyslipidemia that accompanies antiretroviral therapy is complicated by drug-drug interactions among several major HIV and lipid-lowering therapies. Further, some of the most lipid-offensive antiretrovirals are the most likely to influence the metabolism of the drugs used to reduce lipids, commonly known as statins.

In this report, John Gerber and colleagues in the AIDS Clinical Trials Group (ACTG) investigated the effect of the popular antiretroviral efavirenz (EFV, Sustiva, Stocrin) on three commonly used statins: simvastatin (Vytorin, Zocor), atorvastatin (Caduet, Lipitor) and pravastatin (Pravachol).

View our poll archive

Fifty-two healthy, HIV-uninfected study participants were administered 1 of these statins for three days, during which the levels of the drug were checked over a 24-hour period. Efavirenz was then administered alone for 12 days and then together with the statin for an additional three days-- allowing for the levels of both drugs when co-administered to be com- pared with those obtained earlier in the study.

Co-administration of efavirenz with simvastatin led to a 58% decline in area under the curve (AUC) and a similar decline in the active metabolite HMG-CoA reductase AUC. For atorvastatin, there was a median 42.7% decline in the AUC of this drug and a 34.5% drop in levels of its active metabolites in the presence of efavirenz. Likewise, the pravastatin AUC was reduced by a median of 40.4% with efavirenz. Efavirenz concentration was unaffected by the statins.

To demonstrate that these changes in AUC are potentially clinically meaningful, the investigators examined the low-density lipoprotein (LDL) cholesterol levels of the participants after the first short course of their statin alone and after the statin with efavirenz. They found a trend toward attenuation of the lipid-lowering effect of the drugs.

This extremely helpful study defines an important and commonplace drug-drug interaction. Efavirenz can contribute to increases in lipids, therefore, the prospect of concomitant administration of this non-nucleoside reverse transcriptase inhibitor (NNRTI) and a statin is indeed real. As a potent inducer of the metabolism of these three statins, efavirenz (and probably nevirapine [NVP, Viramune], given its known induction of CYP3A4) can significantly reduce the levels of these drugs. As such, the dosing of the studied statins, when co-administered with efavirenz, will likely need to be increased to achieve a desired lipid-lowering effect. Clinicians can feel less anxious about initiating a higher dose of statin than usual (above the lowish starting doses we typically use) when NNRTIs are on board, but should continue to apply the proper side-effect surveillance.

Editor's Note: from theBodyPro.com