ABSTRACT
No disponible
Subject(s)
Humans , Diphosphonates/adverse effects , /epidemiology , Risk Factors , Osteoporosis/drug therapyABSTRACT
El desarrollo del tratamiento antirretroviral (TAR) hasta lascombinaciones actuales con 3 fármacos ha permitido unadisminución considerable de la mortalidad y la morbilidaden los pacientes infectados por el virus de lainmunodeficiencia humana. Sin embargo, hay unanecesidad de tratamientos menos tóxicos sin sacrificar sueficacia y más baratos para facilitar el acceso universal aestas medicaciones. El perfil farmacocinético favorable y laalta barrera genética de los inhibidores de la proteasa (IP)administrados con ritonavir hacen de ellos candidatosideales para el uso en monoterapia, con lo cual se evita latoxicidad y el coste asociados al uso de análogos de losnucleósidos, además de preservar fármacos para opcionesfuturas. Los resultados prometedores de los estudiosrealizados con lopinavir potenciado con ritonavir (LPV/r)en pautas de simplificación y de inducción-mantenimiento,en pacientes sin fracaso previo a inhibidores de laproteasa, favorecen la investigación del coste-efectividadde LPV/r en monoterapia desde el inicio del TAR. Lospocos estudios realizados en este sentido parecen indicarque: a) la monoterapia con LPV/r consigueindetectabilidad en una importante proporción depacientes no tratados; b) en los que ésta no se consigue,no afecta a opciones futuras de tratamiento, ya que espoco probable que se produzcan mutaciones de resistenciay la intensificación del tratamiento permite alcanzar lasupresión de la replicación viral, y c) probablemente sepuedan plantear estrategias de detección temprana de lospacientes en los que la monoterapia con LPV/r no va a sercompletamente supresora. No obstante, para poderplantear la monoterapia con LPV/r como una opción detratamiento de primera línea, son necesarios nuevosestudios, más amplios y con seguimiento más largo, conuna atención particular a la replicación viral en lugares enlos que los IP tienen menos penetración(AU)
The development of antiretroviral therapy (ART) withcurrent triple drug combinations has dramatically reducedmorbidity and mortality in HIV-infected patients. However,there is a need for less toxic treatments without sacrificingefficacy, as well as for less expensive drugs to facilitateuniversal access to this therapy. The protease inhibitors(PI) administered with ritonavir have a favorablepharmacokinetic profile and high genetic barrier andconsequently are ideal candidates for use in monotherapy,thus avoiding the toxicity and cost associated withnucleoside analogs, as well as preserving drugs for futureoptions. The promising results of studies performed withlopinavir/ritonavir (LPV/r) in induction-maintenanceregimens in patients without prior failure to PIs encourageresearch into the cost-effectiveness of LPV/r inmonotherapy from the beginning of ART. The few studiesperformed in this context seem to indicate the following:a) LPV/r monotherapy achieves undetectable viral loads ina large proportion of treatment-naïve patients, b) futuretreatment options are not compromised in patients notachieving undetectable viral loads since the likelihood ofresistance mutations is low and treatment intensificationachieves suppression of viral replication, and c) strategiesfor early detection can probably be considered in patientswho will not achieve complete suppression with LPV/rmonotherapy. Nevertheless, before LPV/r monotherapycan be considered a first-line option, new studies withlarger samples and longer follow-up are required. Thesestudies should pay particular attention to viral replicationin areas where PI show less penetration(AU)
Subject(s)
Humans , HIV Protease Inhibitors/pharmacokinetics , Anti-Retroviral Agents/pharmacokinetics , HIV Infections/drug therapy , Ritonavir/pharmacokinetics , Antiretroviral Therapy, Highly Active , HIV , Virus ReplicationABSTRACT
The development of antiretroviral therapy (ART) with current triple drug combinations has dramatically reduced morbidity and mortality in HIV-infected patients. However, there is a need for less toxic treatments without sacrificing efficacy, as well as for less expensive drugs to facilitate universal access to this therapy. The protease inhibitors (PI) administered with ritonavir have a favorable pharmacokinetic profile and high genetic barrier and consequently are ideal candidates for use in monotherapy, thus avoiding the toxicity and cost associated with nucleoside analogs, as well as preserving drugs for future options. The promising results of studies performed with lopinavir/ritonavir (LPV/r) in induction-maintenance regimens in patients without prior failure to PIs encourage research into the cost-effectiveness of LPV/r in monotherapy from the beginning of ART. The few studies performed in this context seem to indicate the following: a) LPV/r monotherapy achieves undetectable viral loads in a large proportion of treatment-naïve patients, b) future treatment options are not compromised in patients not achieving undetectable viral loads since the likelihood of resistance mutations is low and treatment intensification achieves suppression of viral replication, and c) strategies for early detection can probably be considered in patients who will not achieve complete suppression with LPV/r monotherapy. Nevertheless, before LPV/r monotherapy can be considered a first-line option, new studies with larger samples and longer follow-up are required. These studies should pay particular attention to viral replication in areas where PI show less penetration.
