I have read that there are fears from some in the medical/scientific community that PI could cause dangerous mutations. (as if it isn't dangerous enough). My understanding is that people taking the cocktails early on kill some of the virus but not all. Those surviving virus live on to reproduce mutated forms
Also, they are toxic. Some have strange effects on people's weight. They call it "protease paunch". Paunches, buffalo humps in the neck, puffy cheeks among other weird things.