Papel de las nuevas moléculas en el tratamiento antirretroviral. Dónde situar el raltegravir | Enfermedades Infecciosas y Microbiología Clínica

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El tratamiento antirretroviral de rescate se ha visto revolucionado por la aparición de nuevos fármacos en los últimos años: enfuvirtida (un inhibidor de la fusión), tipranavir/ritonavir (inhibidor de la proteasa de alta barrera genética), darunavir/ritonavir (inhibidor de la proteasa de alta barrera genética), etravirina (no nucleósido activo contra el virus de la inmunodeficiencia humana [VIH] resistente a nevirapina y efavirenz), maraviroc (un inhibidor de los correceptores CCR5) y raltegravir (un inhibidor de la integrasa). La utilización de estos fármacos en pautas de rescate ha hecho posible que el objetivo de la terapia antirretroviral de rescate sea el mismo que en pacientes naïve: alcanzar una carga viral menor de 50 copias/ml de ARN de VIH. Raltegravir es el primer inhibidor de la integrasa disponible para los clínicos en España. Su vía principal de metabolización es glucuronidación mediada por UGT1A1 por lo que tiene un bajo potencial de interacciones con fármacos que se metabolizan por la vía del citocromo P450. Raltegravir ha demostrado alta eficacia en 2 grandes ensayos clínicos de rescate, especialmente cuando se ha combinado con darunavir/ritonavir y enfuvirtida. Los datos preliminares apuntan a que raltegravir también podrá ser un fármaco eficaz para el tratamiento de pacientes naïve y como terapia de sustitución en pacientes que tengan toxicidad relacionada con inhibidores de la proteasa potenciados. Su mecanismo peculiar de acción ha planteado de nuevo la posibilidad de un impacto positivo de raltegravir en los reservorios de latencia del VIH.

Palabras clave:

Raltegravir

Darunavir/zitomavir

Entravirina

Maraviroc

Enfuvirtida

Tipranavir/zitomavir

VIH

Resistencia

Antiretroviral rescue therapy has been revolutionized by the development of new drugs in the last few years: enfuvirtide (a fusion inhibitor), tipranavir/ritonavir (a high genetic barrier protease inhibitor), darunavir/ritonavir (a high genetic barrier protease inhibitor), etravirine (a non-nucleoside reverse transcriptase inhibitor active against nevirapine- and efavirenz- resistant HIV), maraviroc (a CCR5 coreceptor inhibitor) and raltegravir (an integrase inhibitor). The use of these drugs in rescue regimens has allowed the goal of antiretroviral rescue therapy to be the same as that in treatment naïve-patients: to achieve a viral load lower than 50 copies of RNA of HIV/ml. Raltegravir is the first integrase inhibitor available for clinical use in Spain. This drug is primarily metabolized through UGT1A1-mediated glucuronidation and consequently has a low potential for interactions with drugs metabolized by the cytochrome P450 pathway. Raltegravir has been demonstrated to have high efficacy in two large clinical trials of rescue therapy, especially when combined with darunavir /ritonavir and enfuvirtide. Preliminary data suggest that raltegravir could also be an effective drug in treatment-naïve patients and as substitution therapy in patients with toxicity due to boosted protease inhibitor therapy. The drug's unusual mechanism of action has reopened the possibility of a positive effect on latent HIV reservoirs.

Key words:

Raltegravir

Darunavir/zitomavir

Entravirine

Maraviroc

Enfuvirtide

Tipranavir/zitomavir

HIV

Resistance

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