Darunavir en primeras líneas. Estudio TITAN / Darunavir in first-live therapy. The TITAN study

Durante muchos años lopinavir/ritonavir (LPV/r) ha sido elestándar de oro del tratamiento de las primeras líneas derescate. Ninguno de los otros inhibidores de la proteasapotenciados (IP/r) había logrado demostrar superioridadfrente a LPV/r. En este escenario, el estudio TITAN comparóen 595 pacientes la eficacia y seguridad de darunavir(DRV)/r a dosis de 600/100 mg 2 veces al día frente a ladosis habitual de LPV/r, asociados al menos a otros 2antirretrovirales optimizados. La eficacia del tratamiento alas 48 semanas (carga viral < 400 copias/ml) resultósignificativamente superior en el grupo de DRV/r que en elde LPV/r, tanto en el análisis por protocolo (el 77 frente al68%), demostrándose la no inferioridad de DRV/r (diferenciaestimada +9%; intervalo de confianza [IC] del 95%, 2-16%),como por intención de tratamiento (el 77 frente al 67%),demostrándose la superioridad de DRV/r (diferenciaestimada del 10%; IC del 95%, 2-17%). La incidencia dediarrea y el aumento de triglicéridos fueron superiores en elgrupo de LPV/r. Las diferencias en la eficacia de ambostratamientos a favor de DRV/r empezaron a observarse apartir de una mutación primaria basal en la proteasa y seincrementaron a medida que aumentó el número de dichasmutaciones. En los pacientes con fallo virológico, DRV/rprotegió a la proteasa y a la transcriptasa inversa frente a laaparición de mutaciones, preservando futuras opcionesterapéuticas. Se dispone de algunos datos teóricos yclínicos que nos permiten pensar en la posibilidad deadministrar DRV/r 1 vez al día en algunos pacientes conpocas mutaciones en la proteasa y en los que se considereimportante esta posología. Con los resultados del estudioTITAN, DRV/r debe considerarse el nuevo estándar de oroen las primeras líneas de rescate, al menos en los pacientescon alguna mutación primaria en la proteasa(AU)

Lopinavir/ritonavir (LPV/r) has been the gold standard infirst line rescue treatment for many years. No other boosted protease inhibitor (PI/r) has managed to demonstrate that itis superior to LPV/r. In this regard, the TITAN studycompared the efficacy and safety of darunavir (DRV/r) in 595patients, at a dose of 600/100 mg two times a day againstthe normal LPV/r dose, combined with at least 2 otheroptimised antiretroviral drugs. The efficacy of the treatmentat 48 weeks (VL<400 copies/mL) was significantly higher inthe DRV/r goup compared to the LPV/r group, both in theanalysis by protocol (77% vs. 68%), the non-inferiority ofDRV/r being demonstrated (estimated difference +9%, 95%CI 2-16), and by intention to treat (77% vs. 67%), thesuperiority of DRV/r being demonstrated (estimateddifference 10%, 95% CI 2-17%). The incidence of diarrhoeaand increase in triglycerides was higher in the LPV/r group.The differences in efficacy of both treatments in favour ofDRV/r started to be seen from a basal primary mutation inthe protease, with these differences increasing as thenumber of these mutations increased. In patients withvirological failure, DRV/r protected the protease and reversetranscriptase against mutations, thus preserving futuretherapeutic options. We have some theoretical and clinicaldata available that enables us to consider the possibility ofadministering DRV/r once a day in some patients with afew mutations in the protease and in those where thisdosing regime is considered important. With the results ofthe TITAN study, DRV/r must be considered the new goldstandard in first line rescue, at least in those patients with aprimary mutation in the protease(AU)

Darunavir en primeras líneas. Estudio TITAN / Darunavir in first-live therapy. The TITAN study

Durante muchos años lopinavir/ritonavir (LPV/r) ha sido el estándar de oro del tratamiento de las primeras líneas de rescate. Ninguno de los otros inhibidores de la proteasa potenciados (IP/r) había logrado demostrar superioridad frente a LPV/r. En este escenario, el estudio TITAN comparó en 595 pacientes la eficacia y seguridad de darunavir (DRV)/r a dosis de 600/100 mg 2 veces al día frente a la dosis habitual de LPV/r, asociados al menos a otros 2 antirretrovirales optimizados. La eficacia del tratamiento a las 48 semanas (carga viral < 400 copias/ml) resultósignificativamente superior en el grupo de DRV/r que en el de LPV/r, tanto en el análisis por protocolo (el 77 frente al 68%), demostrándose la no inferioridad de DRV/r (diferencia estimada +9%; intervalo de confianza [IC] del 95%, 2-16%), como por intención de tratamiento (el 77 frente al 67%), demostrándose la superioridad de DRV/r (diferencia estimada del 10%; IC del 95%, 2-17%). La incidencia de diarrea y el aumento de triglicéridos fueron superiores en el grupo de LPV/r. Las diferencias en la eficacia de ambos tratamientos a favor de DRV/r empezaron a observarse a partir de una mutación primaria basal en la proteasa y se incrementaron a medida que aumentó el número de dichas mutaciones. En los pacientes con fallo virológico, DRV/r protegió a la proteasa y a la transcriptasa inversa frente a la aparición de mutaciones, preservando futuras opcionesterapéuticas. Se dispone de algunos datos teóricos yclínicos que nos permiten pensar en la posibilidad deadministrar DRV/r 1 vez al día en algunos pacientes conpocas mutaciones en la proteasa y en los que se considereimportante esta posología. Con los resultados del estudioTITAN, DRV/r debe considerarse el nuevo estándar de oroen las primeras líneas de rescate, al menos en los pacientes con alguna mutación primaria en la proteasa

Lopinavir/ritonavir (LPV/r) has been the gold standard infirst line rescue treatment for many years. No other boosted protease inhibitor (PI/r) has managed to demonstrate that it is superior to LPV/r. In this regard, the TITAN study compared the efficacy and safety of darunavir (DRV/r) in 595 patients, at a dose of 600/100 mg two times a day against the normal LPV/r dose, combined with at least 2 other optimised antiretroviral drugs. The efficacy of the treatmentat 48 weeks (VL<400 copies/mL) was significantly higher in the DRV/r goup compared to the LPV/r group, both in the analysis by protocol (77% vs. 68%), the non-inferiority of DRV/r being demonstrated (estimated difference +9%, 95% CI 2-16), and by intention to treat (77% vs. 67%), the superiority of DRV/r being demonstrated (estimated difference 10%, 95% CI 2-17%). The incidence of diarrhoea and increase in triglycerides was higher in the LPV/r group. The differences in efficacy of both treatments in favour of DRV/r started to be seen from a basal primary mutation inthe protease, with these differences increasing as thenumber of these mutations increased. In patients withvirological failure, DRV/r protected the protease and reverse transcriptase against mutations, thus preserving future therapeutic options. We have some theoretical and clinical data available that enables us to consider the possibility of administering DRV/r once a day in some patients with a few mutations in the protease and in those where this dosing regime is considered important. With the results of the TITAN study, DRV/r must be considered the new gold standard in first line rescue, at least in those patients with a primary mutation in the protease

[Darunavir as first-line therapy. The TITAN study]. / Darunavir en primeras líneas. Estudio TITAN.

Lopinavir/ritonavir (LPV/r) has been the gold standard in first line rescue treatment for many years. No other boosted protease inhibitor (PI/r) has managed to demonstrate that it is superior to LPV/r. In this regard, the TITAN study compared the efficacy and safety of darunavir (DRV/r) in 595 patients, at a dose of 600/100 mg two times a day against the normal LPV/r dose, combined with at least 2 other optimised antiretroviral drugs. The efficacy of the treatment at 48 weeks (VL<400 copies/mL) was significantly higher in the DRV/r goup compared to the LPV/r group, both in the analysis by protocol (77% vs. 68%), the non-inferiority of DRV/r being demonstrated (estimated difference +9%, 95% CI 2-16), and by intention to treat (77% vs. 67%), the superiority of DRV/r being demonstrated (estimated difference 10%, 95% CI 2-17%). The incidence of diarrhoea and increase in triglycerides was higher in the LPV/r group. The differences in efficacy of both treatments in favour of DRV/r started to be seen from a basal primary mutation in the protease, with these differences increasing as the number of these mutations increased. In patients with virological failure, DRV/r protected the protease and reverse transcriptase against mutations, thus preserving future therapeutic options. We have some theoretical and clinical data available that enables us to consider the possibility of administering DRV/r once a day in some patients with a few mutations in the protease and in those where this dosing regime is considered important. With the results of the TITAN study, DRV/r must be considered the new gold standard in first line rescue, at least in those patients with a primary mutation in the protease.