This review addresses the current landscape of PIs, the primary PR mutations that confer drug resistance, and identifies three classes of novel PIs that warrant consideration for anti-HIV drug development: (i) novel PIs exhibiting robust inhibitory activity that target the traditional active, non-active and cleavage sites of PR; (ii) novel PIs designed to target drug-resistant PR variants, particularly those associated with multi-drug resistant (MDR) HIV isolates; and (iii) novel PIs that engage multiple stages of HIV replication, thereby enhancing the anti-HIV efficacy of PIs.
Gu et al. (Mon,) studied this question.