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Los inhibidores de la integrasa son la familia de antirretrovirales más recientemente aprobada para el tratamiento de la infección por el virus de la inmunodeficiencia humana (VIH). Al igual que sucede con el resto de los antirretrovirales, bajo presión farmacológica el virus selecciona mutaciones de resistencia si la supresión viral no es completa. Se seleccionan mutaciones en el gen de la integrasa, concretamente en posiciones próximas al centro catalítico. La experiencia clínica con estos fármacos es escasa, de modo que la información sobre resistencias es limitada. Los fracasos a raltegravir se asocian a selección de mutaciones primarias como N155H (40%) y diferentes cambios en la posición Q148 (28%). Con menor frecuencia se seleccionan Y143R (6,6%) y E92Q. Las mutaciones más frecuentemente observadas en los fracasos a elvitegravir son E92Q, E138K, Q148R/K/H y N155H, y con menor frecuencia S147G y T66A/I/K. El patrón de resistencias más común parece ser E138K + E147G + Q148R. Hay un alto grado de resistencia cruzada entre raltegravir y elvitegravir que imposibilitará la secuenciación entre ellos.
Palabras clave:
Raltegravir
Resistencia
Integrasa
VIH
Integrase inhibitors are the most recently approved family of antiretroviral agents for the treatment of HIV infection. As with other antiretroviral agents, under pharmacological pressure, the virus selects resistance mutations if viral suppression is incomplete. Mutations are selected in the integrase gene, specifically in positions proximal to the catalytic center. Because clinical experience with these drugs is scarce, information on resistance is limited. Virologic failure with raltegravir is associated with selection of primary mutations such as N155H (40%) and distinct changes in position Q148 (28%). Less frequently, Y143R (6.6%) and E92Q are selected. The most frequently observed mutations in failure with elvitegravir are E92Q, E138K, Q148R/K/H and N155H, and less frequently S147G and T66A/I/K. The most common resistance pattern seems to be E138K + E147G + Q148R. There is a high grade of cross resistance between raltegravir and elvitegravir, making sequencing between these two drugs impossible.
Key words:
Raltegravir
Resistance
Integrase
HIV
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