Darunavir exhibits less than a 10-fold decrease in susceptibility in cell culture against 90% of 3309 clinical isolatesresistant to amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir.In contrast, darunavir-resistant viruses display limited susceptibility to only tipranavir, suggesting limited cross-resistance between these two protease inhibitors.To avoid the issues of the peptide-based protease inhibitors, darunavir has evolved from a structure-based design effort to minimize peptidic features and reduce molecular weight and complexity.