his article summarizes the discovery, activity, molecular mechanism and structural optimization of nonpeptide sulfonamide anti-HIV (human immunodeficienty virus) protease inhibitor darunavir (TMC-114), which has not only a good inhibitory effect on wildtype HIV protease, but also fantastic inhibitory effects on many mutated HIV proteases, and is a new drug developed for HIV’s resistance.

Key words: darunavir (TMC-114), acquired immure deficiency syndrome (AIDS), resistant mutati, HIV protease inhibitor