Etravirine is a recently approved nonnucleoside reverse transcriptase inhibitor. The ability of etravirine to limit the emergence of resistance to protease inhibitors, and specifically to darunavir, was investigated in the subset of treatment-experienced patients with virologic rebound in the phase III DUET trials. Of those experiencing rebound, fewer etravirine-treated than placebo-treated patients developed mutations associated with resistance to protease inhibitors in general and to darunavir in particular, and more patients in the etravirine than the placebo-group maintained baseline darunavir susceptibility at endpoint.