Mecanismos de resistencia y fracaso al tratamiento con maraviroc | Enfermedades Infecciosas y Microbiología Clínica

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Maraviroc (MVC) es un nuevo antagonista del correceptor CCR5 y es el primer compuesto antiviral disponible que tiene como diana un factor celular imprescindible para la entrada del VIH. La información disponible en estudios clínicos con MVC indica que la causa principal del fallo terapéutico es, más que el cambio de tropismo, la rápida selección de cepas preexistentes con afinidad por CXCR4 no detectadas por la prueba de referencia. Una prueba de tropismo con sensibilidad mejorada recientemente desarrollado contribuirá a detectar la presencia minoritaria, pero clínicamente significativa, de cepas que utilizan CXCR4. La resistencia a MVC se ha podido evidenciar in vivo en algunos pacientes. El mecanismo de esta resistencia parece estar relacionado con cambios en gp120 y, fundamentalmente, en la región V3 que permiten al virus reconocer el correceptor CCR5 unido a la molécula de MVC. Desde un punto de vista práctico, no disponemos por el momento de pruebas estandarizadas para evaluar la susceptibilidad a MVC, aunque en las pruebas fenotípicas de dosis-respuesta un porcentaje máximo de inhibición (MPI) < 95% sería indicativo de resistencia al compuesto. Igualmente, aunque se han descrito algunas mutaciones relacionadas con resistencia en V3 y otras zonas de gp120, esta información preliminar indica diferentes patrones de resistencia y desconocemos por el momento las mutaciones canónicas para poder establecer algoritmos de genotipificación.

Palabras clave:

Maraviroc

CCR5

CXCR4

Resistencia

Tropismo

Maraviroc (MVC) is a new antagonist of the CCR5 coreceptor and is the first antiviral compound available that has a cell factor essential for HIV entry as a target. The information available from clinical studies with MVC suggests that the main cause of therapeutic failure is, more than the tropism change, the rapid selection of pre-existing strains with an affinity for CXCR4, not detected by the reference test. A recently developed tropism test with an improved sensitivity will help to detect the minority, but clinically significant, presence of strains that use CXCR4. Evidence of resistance to MVC has been shown in vivo in some patients. The mechanism of this resistance appears to be related to changes in gp120 and mainly in the V3 region which enables the virus to recognise the CCR5-co-receptor bound to the MVC molecule. From a practical point of view, standardised tests are currently unavailable to assess susceptibility to MVC, although in dose-response phenotype tests a maximum percentage inhibition (MPI) < 95% would be indicative of resistance to the compound. Similarly, although some mutations associated with resistance in V3, and other zones of gp120, have been described, this preliminary information suggests different resistance patterns and at the moment, we do not know the canonical mutations to be able to establish genotyping algorithms.

Key words:

Maraviroc

CCR5

CXCR4

Resistance

Tropism

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