[Etravirine: genetic barrier and resistance development].

Unlike first-generation non-nucleoside reverse transcriptase inhibitors (NNRTI), to develop complete resistance to etravirine (ETR), various mutations must be accumulated. This drug shows an intermediate barrier against partial resistance and a high barrier to complete resistance. Some mutations selected by nevirapine or efavirenz affect the activity of ETR, the most frequent being Y181C, G190A/S, K101E, L100I, Y188L and V90I. The grade of resistance conferred by each mutation differs. Currently, there are at least three lists of mutations that confer an exact score to each mutation. These lists have been validated with the grade of resistance observed in paired phenotypes and with clinical response in the DUET studies. The three scores show a high degree of agreement. ETR is currently one of the antiretroviral drugs whose activity can be calculated simply and accurately on the basis of genotypic data. The mutations selected after failure to nucleoside reverse transcriptase inhibitors, thymidine analogue, T69D/N and M184I/V, confer hypersusceptibility to ETR (fold change < 0.4) in up to 1 out of every 3 samples analyzed. The early withdrawal of first-generation NNRTIs in patients with virological failure is essential to avoid the accumulation of mutations that could compromise the activity of this drug.