**6. Protease inhibitors**

Protease inhibitors (PI's) interfere with replication of viruses, maturation and infection of new viral cells by inhibiting the cleavage of enzyme necessary for viral protein precursors. Like NNRTI's, protein inhibitors are also metabolized by cytochrome P450 enzymes which leads to drug-drug interaction. PI's can also cause gastrointestinal side (GI's) effects and elevation in liver transaminase enzyme. Some protease inhibitors like saquinavir have first pass metabolic effect which results poor bioavailabilty which may be improved by administrating with food.

Physiological factors like achlorhydria, malabsorption and poor hepatic dysfunction may impair the bioavailability of protease inhibitors in HIV infections which may influence their antiHIV activity *in vitro*. PI's like ritonavir and indinavir may displace other protease inhibitors like saquinavir, from plasma protein and inhibit their metabolism. In addition PI's can worsen diabetes, insulin resistance, hypercholesterolemia, hypertension and hyperlipidemia [26].
