Shifting paradigms: the resistance profile of etravirine

The raised genetic barrier of etravirine relative to first-generation compounds indicates that it may now be possible to sequence drugs within the non-nucleoside reverse transcriptase inhibitor (NNRTI) class. Available evidence from clinical trials provides guidance for the use of etravirine in NNRTI-experienced persons, with sustained virological suppression demonstrated in combination with other active drugs in the background regimen, most commonly including a ritonavir-boosted protease inhibitor with or without enfuvirtide. Cross-resistance occurs however, and the drug is vulnerable to loss of activity in the absence of a supportive background regimen. In order to optimize the use of etravirine in clinical practice, it is important to understand how current predictors of virological activity in NNRTI-experienced persons were developed, how they can be applied, and the adjustments and improvements they require.