Overcoming HIV-1 resistance to protease inhibitors

Protease inhibitors are key components in the chemotherapy of HIV-1 infection. However, despite their success, the appearance of viral mutations routinely compromises their clinical efficacy, creating a constant need for new and better inhibitors. An ideal inhibitor should be able to neutralize the wild type as well as mutants associated with drug resistance with high potency and high selectivity towards human targets, thus minimizing side effects. The evolution of protease inhibitors since 1995 has revealed the basis for extremely high affinity as well as different mechanisms by which inhibitors can escape the deleterious effects of mutations.

Section editors:William Bishai and Eric Nuermberger – Johns Hopkins School of Medicine, Baltimore, MD, USA