Conclusiones y perspectivas | Enfermedades Infecciosas y Microbiología Clínica

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Se discuten los aspectos más destacados de maraviroc expuestos en esta monografía, las perspectivas de desarrollo y aplicación de este fármaco, así como las principales preguntas planteadas en su utilización.

Maraviroc es el primer antagonista de CCR5 aprobado para el tratamiento de la infección por el VIH. Su estructura imidazopiridina interactúa con CCR5 e induce una conformacion del correceptor que impide la unión de las glucoproteínas de la envuelta viral. Tiene una potente actividad antiviral y actúa sobre un amplio espectro de virus con afinidad por este receptor. Esta circunstancia obliga a realizar un test de tropismo previo al tratamiento para definir si el paciente es portador de variantes R5. Maraviroc está indicado en pacientes infectados por el VIH que han recibido tratamiento antirretroviral previo. Presenta una baja toxicidad y, según los datos preliminares, una alta barrera genética. El mecanismo de resistencia se relaciona con cambios en la región V3 que permiten al virus reconocer el correceptor CCR5 unido a la molécula de maraviroc. La causa principal de fallo terapéutico es la selección de cepas X4 preexistentes no detectadas por la prueba de referencia. Maraviroc puede asociarse con cualquier antirretroviral comercializado o en desarrollo clínico avanzado. Las indicaciones de maraviroc en fases tempranas de la infección no es recomendada en el momento actual y dependerá de la demostración de no inferioridad respecto a otros tratamientos o de un beneficio en otros aspectos patogénicos como la recuperación de linfocitos CD4 o la reducción de los reservorios virales.

Palabras clave:

CCR5

Agonista inverso

Resistencia

Tropismo viral

This monograph discusses most important aspects Maraviroc, the development and application perspectives of this drug, as well as main questions raised in its use.

Maraviroc is the first CCR5 antagonist approved for treating HIV infection. Its imidazopyridine structure interacts with CCR5 and induces a co-receptor conformation that prevents glycoproteins binding to the viral envelope. It has powerful antiviral activity and acts on a wide spectrum of viruses with affinity for this receptor. This situation means that a tropism test has to be done before treatment to define whether the patient is a carrier of R5 variants. Maraviroc is indicated in HIV infected patients who have received previous antiretroviral treatment. It has a low toxicity and, according to preliminary data, a high genetic barrier. The resistance mechanism is associated with changes in the V3 region which allow the virus to recognise the CCR5 co-receptor bound to the Maraviroc molecule. The main cause of treatment failure is the selection of pre-existing X4 strains not detected by the reference test. Maraviroc can be combined with any other antiretroviral on the market or in clinically advanced development. The indication of Maraviroc in the early phases of the infection is not currently recommended and will depend whether it is shown to be inferior when compared other treatments or a benefit in other pathogenic aspects, such as recovery of CD4 lymphocytes or a reduction in viral reservoirs.

Key words:

CCR5

Inverse agonist

Resistance

Viral tropism

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