[Viral resistance and genetic barrier of atazanavir]

Abstract

Resistance to protease inhibitors (PI) is generally due to a mutation in the protease gene. Different changes have been described for each PI. The I 50L mutation is characteristic of resistance to atazanavir (ATV). It does not produce cross resistance to other PI; but it does increase susceptibility to all of them (hypersusceptibility). When PI are given concomitantly with low doses of ritonavir, the exposure to higher levels of PI requires that multiple resistance mutations have to be selected in the protease so that there is a significant loss of susceptibility. For the majority of PI/r, including ATV/r, >or=5 mutations in the protease are required to produce a compromise in the virological response. Despite having a moderate genetic barrier when not boosted with ritonavir, the prolonged half life of ATV minimises the risk of resistance in clinical practice.