There is also growing concern with reports of long QT syndrome and torsade de pointes in IDUs. This patient group have several risk factors that increase their susceptibility. Methadone is well recognised to cause long QT syndrome and torsades de pointes through inhibition of a cardiac potassium channel, the major component of which is encoded by the human ether-a-go-go gene (HERG). Multiple HERG polymorphisms have been identified that are clinically silent but may confer vulnerability to arrhythmia by a triggering event. Protease inhibitors also have the potential to cause QT prolongation. This may be mediated by direct effects on HERG channels or by potentiating the effects of other drugs through inhibition of CYP3A, or both. Concurrent use of protease inhibitors and methadone might pose an additive risk of QT prolongation and a few cases have been reported recently. Additionally, co-infection with hepatitis C is also recognised to prolong the QT interval.