Personally I do not believe we know enough about protease or non protease inhibitors. It has been stated that PI s interferes with the body's natural protease enzyme and is not HIV protease specific. Plus the fact protease inhibitors have contributed to lipodystrophy. Lipodystrophy is fat redistribution in the visceral organs, observed thinning of the extremities, prominence of veins, increased wrinkles in the face and loss of fat under the skin.
Visceral organs are the internal organs such as the stomach, kidney, liver, etc.
This has been called the crix belly, protease paunch. Clinical studies are run at shorther and shorter time frames. Data is released at 24 to 36 weeksat conferences, seeking FDA approval. Unfortunately patients have to take these medication for life NOT 24 or 35 weeks. Side effects and long term toxicity is only discoverd as patients take the medications for a year and longer.