Información del artículo
La resistencia a los inhibidores de la proteasa (IP) generalmente es consecuencia de una mutación en el gen de la proteasa. Se han descrito distintos cambios para cada uno de los IP. La mutación I50L es la característica de resistencia al atazanavir (ATV). No produce resistencia cruzada con otros IP; por el contrario, aumenta la susceptibilidad a todos ellos (hipersusceptibilidad). Cuando los IP se administran conjuntamente con dosis bajas de ritonavir (r), la exposición a concentraciones más elevadas de IP hace necesaria la selección de múltiples mutaciones de resistencia en la proteasa para que haya una pérdida significativa de susceptibilidad. Para la mayoría de IP/r, incluido el ATV/r, se requieren ≥ 5 mutaciones en la proteasa para ocasionar un compromiso en la respuesta virológica. A pesar de tener una moderada barrera genética cuando no se potencia con ritonavir, la prolongada semivida del ATV minimiza el riesgo de resistencias en la práctica clínica.
Palabras clave:
Atazanavir
Resistencias
Inhibidores de la proteasa
VIH
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, ≥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.
Key words:
Atazanavir
Resistances
Protease inhibitors
HIV
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