Protease Inhibitors for Patients With HIV-1 Infection: A Comparative Overview.

protein. Gag and gag–pol must be cleaved at specific points in order to produce functional proteins. HIV-1 protease is responsible for the cleavage of the gag and gag–pol polyproteins into their functional constituent proteins, including the release of the protease itself from the gag–pol precursor.14 This key step in the maturation process of HIV-1 occurs during the final stages of the HIV life cycle as the virion buds from host cells. Regulation of HIV protease activity in the virus-replication cycle is critical for proper assembly and maturation of HIV polyproteins to produce the infectious virus.15 Thus, inhibition of HIV protease causes the release of immature and noninfectious particles. PIs used for treating HIV infection are designed to tightly bind HIV protease, but they tend to be bulkier than the natural substrates.15 Most PIs are prescribed with concomitant lowdose RTV as a boosting agent because of their pharmaco kinetic properties. Except for TPV, all PIs are competitive pep tidomimetic inhibitors that mimic the natural substrate of the viral protease.15,16 These compounds contain a hydroxyethylene core that mimics the transition state intermediate formed during protease catalysis.15,16 TPV is classified as a nonpeptidomimetic PI, and it contains a dihydropyrone ring as a central scaffold. This drug is designed to stabilize binding through better interactions at key regions of the protease active site.15