Protease inhibitors may promote arrhythmias at risk of sudden death

Antiretroviral class of protease inhibitors appear to be associated with a risk of inducing QT interval prolongation and torsades de pointes, cardiac arrhythmias can lead to sudden death, reveal for the first time American doctors .
Dr. B. Anson at the University of Wisconsin at Madison and his colleagues are interested in this issue after having the case of a patient with HIV treated by HAART, with an episode of severe arrhythmias associated with prolongation of the QT interval.

The doctors performed a search in pharmacovigilance data to the FDA and found 23 cases of HIV-positive patients presented with QT prolongation and torsades de pointes while under antiretroviral treatment. All these treatments included protease inhibitors and in half the cases the protease was directly suspected.

To clarify the role of this class of drugs, they have conducted in vitro studies. First, in a system of cells expressing the gene, which encodes the HERG potassium channel responsible for the current blocking repolarization which is generally responsible for long QT, they evaluated the effect of several protease inhibitors.

The four drugs tested induced a dose-dependent block of HERG channel.

A second experiment was performed on cardiac cells in vitro, with one of them. This blocked the potassium current repolarization.

These results are consistent with the hypothesis of a "new side effect of protease inhibitors." It could be a "class effect".

Its importance in number is difficult to determine the extent "given the system [pharmacovigilance], the relative frequency extensions of QT protease inhibitors can not be estimated with our data."

But this discovery could complicate the treatment of HIV infection. On the one hand, we should avoid combining protease inhibitors with other drugs that also prolong the QT and become vigilant vis-à-vis other medications that patients may receive.

In addition, some drugs interfere with cytochrome P450s that metabolize protease inhibitors, and may in some cases increase the concentration of protease, thus indirectly increasing the risk of QT prolongation.

The researchers point out, in conclusion, that these first results on this new potential side effect of protease inhibitors "should in no way limit the enthusiasm of clinicians for use as needed." It should however be paid to the dosage and consider better monitoring, they say.