Deprescribing of non-antiretroviral therapy in HIV-infected patients.

PURPOSE: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. METHODS: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. RESULTS: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. CONCLUSIONS: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.

Prevalencia de las potenciales interacciones medicamentosas entre los antivirales de acción directa pangenotípicos y la medicación concomitante asociada a los pacientes con infección del virus de la hepatitis C crónica en España / Prevalence of the potential drug-drug interactions between pangenotypic direct-acting antivirals and the concomitant medications associated with patients with chronic hepatitis C virus infection in Spain

Objetivo: Determinar la comorbilidad y las potenciales interacciones-farmacológicas (IFs) entre los antivirales de acción-directa pangenotípicos (AADp) y la medicación-concomitante asociada a los pacientes con hepatitis C crónica (HCC) en práctica clínica habitual en España. Métodos: Diseño observacional retrospectivo. Se incluyeron pacientes ≥18 años con diagnóstico de HCC, en tratamiento antiviral y visitados durante el año 2017. Se diferenciaron 2 grupos en función de la edad (<50 y ≥50 años). Las variables recogidas fueron: edad, género, comorbilidad general/específica, medicación-concomitante y potenciales IFs (www.hep-druginteractions.org). Los AADp analizados fueron: a) sofosbuvir/velpatasvir (SOF/VEL); b) glecaprevir/pibrentasvir; y c) sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). Análisis-estadístico bivariante: p<0,05. Resultados: Se reclutaron 3.430 pacientes, edad-media de 56,9 años y el 60,3% varones. El promedio del índice Charlson fue 0,8 puntos. Distribución por rangos de edad: 18-49 (28,9%) y ≥50 años (71,1%). El promedio de medicamentos fue: 3,1 (DE: 2,6) por paciente. El porcentaje total de potenciales IFs fue: 8,6% débil, 40,5% clínicamente significativas y 10,0% medicación contraindicada. Estas interacciones fueron mayores en los pacientes ≥50 años (8,6%; 43,8% y 12,4%, respectivamente, p<0,001). Para todas las edades SOF/VEL en comparación con glecaprevir/pibrentasvir y SOF/VEL/VOX presentó un menor porcentaje de interacciones-débiles (1,3% vs. 6,6% y 5,9%, p<0,001); interacciones clínicamente-significativas (53,4%, vs. 77,4% y 66,3%, p<0,001) y medicación-contraindicada (1,7% vs. 8,3% y 10,7%, p<0,001). Conclusiones: Los sujetos con HCC presentan una elevada comorbilidad y consumo de medicación concomitante, especialmente en pacientes mayores, circunstancia que repercute en una mayor exposición a potenciales IFs. Aunque la tasa de IFs fue considerable con las 3 combinaciones analizadas, SOF/VEL mostró una menor proporción clínicamente relevante

Objective: To determine the comorbidity and potential for drug-drug interactions (DDIs) among pangenotypic direct-acting-antivirals (pDAAs) and the concomitant medications associated with chronic hepatitis C (CHC) patients in routine clinical practice in Spain. Methods: Retrospective observational study. Included patients were ≥18 years, diagnosed with CHC, on antiviral treatment and required medical attention during 2017. Two groups were differentiated according to age ranges (<50 and ≥50 years). The variables collected were: age, gender, general/specific comorbidity, concomitant medication and potential DDIs (www.hep-druginteractions.org). The pDAAs analysed were: a) Sofosbuvir/Velpatasvir (SOF/VEL), b) Glecaprevir/Pibrentasvir (GLE/PIB) and c) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX). Bivariate statistical analysis, P<.05. Results: 3,430 patients with a mean age of 56.9 years and 60.3% males were enrolled. The average Charlson index was 0.8. Age range distribution: 18-49 years (28.9%) and ≥50 years (71.1%). The average number of medications per patient/year was 3.1 (SD 2.6). The total percentage of potential DDIs was: 8.6% minor DDIs, 40.5% clinically significant DDIs and 10.0% contraindicated medication. These DDIs were greater in patients ≥50 years (8.6%, 43.8% and 12.4%, respectively, P<.001). For all ages, SOF/VEL showed a lower percentage of: minor interactions (1.3% vs. 6.6% and 5.9%, P<.001); clinically significant interactions (53.4%, vs. 77.4% and 66.3%, P<.001) and contraindicated medication (1.7% vs. 8.3% and 10.7%, P<.001) compared to GLE/PIB and SOF/VEL/VOX, respectively. Conclusions: Patients with CHC present high comorbidity and concomitant medication use, particularly elderly patients, thus implying a greater exposure to potential DDIs. Although the DDI rate was considerable with the three combinations analysed, SOF/VEL showed a lower number of clinically significant interactions

Prevalence of the potential drug-drug interactions between pangenotypic direct-acting antivirals and the concomitant medications associated with patients with chronic hepatitis C virus infection in Spain. / Prevalencia de las potenciales interacciones medicamentosas entre los antivirales de acción directa pangenotípicos y la medicación concomitante asociada a los pacientes con infección del virus de la hepatitis C crónica en España.

OBJECTIVE: To determine the comorbidity and potential for drug-drug interactions (DDIs) among pangenotypic direct-acting-antivirals (pDAAs) and the concomitant medications associated with chronic hepatitis C (CHC) patients in routine clinical practice in Spain. METHODS: Retrospective observational study. Included patients were ≥18 years, diagnosed with CHC, on antiviral treatment and required medical attention during 2017. Two groups were differentiated according to age ranges (<50 and ≥50 years). The variables collected were: age, gender, general/specific comorbidity, concomitant medication and potential DDIs (www.hep-druginteractions.org). The pDAAs analysed were: a) Sofosbuvir/Velpatasvir (SOF/VEL), b) Glecaprevir/Pibrentasvir (GLE/PIB) and c) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX). Bivariate statistical analysis, P<.05. RESULTS: 3,430 patients with a mean age of 56.9 years and 60.3% males were enrolled. The average Charlson index was 0.8. Age range distribution: 18-49 years (28.9%) and ≥50 years (71.1%). The average number of medications per patient/year was 3.1 (SD 2.6). The total percentage of potential DDIs was: 8.6% minor DDIs, 40.5% clinically significant DDIs and 10.0% contraindicated medication. These DDIs were greater in patients ≥50 years (8.6%, 43.8% and 12.4%, respectively, P<.001). For all ages, SOF/VEL showed a lower percentage of: minor interactions (1.3% vs. 6.6% and 5.9%, P<.001); clinically significant interactions (53.4%, vs. 77.4% and 66.3%, P<.001) and contraindicated medication (1.7% vs. 8.3% and 10.7%, P<.001) compared to GLE/PIB and SOF/VEL/VOX, respectively. CONCLUSIONS: Patients with CHC present high comorbidity and concomitant medication use, particularly elderly patients, thus implying a greater exposure to potential DDIs. Although the DDI rate was considerable with the three combinations analysed, SOF/VEL showed a lower number of clinically significant interactions.

[HIV in Spain 2017: policies for a new management of chronicity beyond virological control]. / VIH en España 2017: políticas para una nueva gestión de la cronicidad más allá del control virológico.

The analysis of the available databases related to HIV/AIDS confirms a paradigm shift in the patient's life expectancy: now HIV has become a chronic disease, so patients are aging. However, this advance is accompanied by a negative counterpart: due to the increase in the number of years of life gained, there is a prevalence of comorbidities greater than the general population and at an earlier age. Reducing the risk associated with all the comorbidities that the ageing patient with HIV/AIDS may develop, must now be a health objective; it must be added to the traditional objectives that until now were part of the strategy to reduce the impact of the HIV infection. In the specific case of women, it is also necessary to train peri and postmenopausal women to increase their skills and motivation to care for their health; It is also very important to examine the role that hormone replacement therapy can play in reducing their symptoms.

El análisis de las bases de datos disponibles relacionadas con VIH/SIDA confirma un cambio de paradigma en la esperanza de vida del paciente: ahora el VIH se ha convertido en una enfermedad crónica, con la que los pacientes están envejeciendo. No obstante, este avance se acompaña de una contraparte negativa: debido al incremento en el número de años de vida ganados, se da una prevalencia de comorbilidades mayor a la de la población general y a una edad más temprana. Reducir el riesgo asociado a todas las comorbilidades que puede desarrollar el paciente con VIH/SIDA mientras envejece debe ser hoy en día un objetivo de salud, que se suma a los objetivos tradicionales que hasta ahora formaban parte de la estrategia para reducir el impacto de la infección por el VIH. En el caso específico de la mujer, además es necesario formar a las mujeres peri y postmenopáusicas para incrementar sus habilidades y su motivación para el cuidado de su salud; también es muy importante que se examine el rol que puede tener la terapia de reemplazo hormonal en la reducción de sus síntomas.

Predictors of primary non-adherence to concomitant chronic treatment in HIV-infected patients with antiretroviral therapy.

OBJECTIVES: To identify the independent risk factors of primary non-adherence to chronic concomitant treatment in HIV-positive patients, and to measure primary and secondary non-adherence rates to chronic treatments, and secondary non-adherence to antiretroviral therapy and the prevalence of concomitant chronic diseases. METHODS: We conducted a retrospective study that included HIV-infected patients with antiretroviral treatmentwho attended the pharmaceutical care office between January and December 2012. The dependent variable was primary non-adherence to concomitant prescription drugs for chronic diseases. To know the predictors of concomitant primary non-adherence, we performed a univariate analysis and a multivariate binary logistic regression model to identify the independent predictors of primary non-adherence to co-medication. RESULTS: Out of 598 patients analysed, 333 patients had a new co-medication prescribed during the studied period. The number of comorbidities per patient was 2.3 and the patients were treated with an average of 3.4 drugs. The rates of primary and secondary non-adherence to co-medication were 8.4% and 44.4%, respectively. The co-occurrence of primary and secondary non-adherence was 24.9%. The number of comorbidities (p=0.001) and co-medications (p=0.001) was significantly higher in patients who had primary non-adherence to co-medication. Furthermore, there was a statistically significant relationship between primary non-adherence and patients treated with psychotropic drugs (p=0.03). The multivariate analysis showed the independent predictor of primary non-adherence to co-medication was the number of co-medications (p<0.001). CONCLUSION: One-third of new concomitant medications prescribed to HIV-positive patients were never filled from the pharmacy. The number of co-medications was identified as a predictor of primary non-adherence to chronic concomitant treatment in HIV-infected population.

VIH en España 2017: políticas para una nueva gestión de la cronicidad más allá del control virológico / HIV in Spain 2017: policies for a new management of chronicity beyond virological control

El análisis de las bases de datos disponibles relacionadas con VIH/SIDA confirma un cambio de paradigma en la esperanza de vida del paciente: ahora el VIH se ha convertido en una enfermedad crónica, con la que los pacientes están envejeciendo. No obstante, este avance se acompaña de una contraparte negativa: debido al incremento en el número de años de vida ganados, se da una prevalencia de comorbilidades mayor a la de la población general y a una edad más temprana. Reducir el riesgo asociado a todas las comorbilidades que puede desarrollar el paciente con VIH/SIDA mientras envejece debe ser hoy en día un objetivo de salud, que se suma a los objetivos tradicionales que hasta ahora formaban parte de la estrategia para reducir el impacto de la infección por el VIH. En el caso específico de la mujer, además es necesario formar a las mujeres peri y postmenopáusicas para incrementar sus habilidades y su motivación para el cuidado de su salud; también es muy importante que se examine el rol que puede tener la terapia de reemplazo hormonal en la reducción de sus síntomas

The analysis of the available databases related to HIV/AIDS confirms a paradigm shift in the patient's life expectancy: now HIV has become a chronic disease, so patients are aging. However, this advance is accompanied by a negative counterpart: due to the increase in the number of years of life gained, there is a prevalence of comorbidities greater than the general population and at an earlier age. Reducing the risk associated with all the comorbidities that the ageing patient with HIV/AIDS may develop, must now be a health objective; it must be added to the traditional objectives that until now were part of the strategy to reduce the impact of the HIV infection. In the specific case of women, it is also necessary to train peri and postmenopausal women to increase their skills and motivation to care for their health; It is also very important to examine the role that hormone replacement therapy can play in reducing their symptoms

Talidomida, peginterferón alfa-2b y ribavirina en el tratamiento de pacientes no respondedores con hepatitis crónica C genotipo 1: estudio piloto / Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept

Antecedentes: menos de la mitad de los pacientes con hepatitis C logra eliminar el virus de manera sostenida después de la terapia con peginterferón alfa y ribavirina (Peg-IFN/RBV). Objetivos: la talidomida posee propiedades antiinflamatorias e inmunomoduladoras a través de la inhibición del TNF-α y al efecto estimulador sobre las células T CD8+. Métodos: se inició un estudio prospectivo y abierto de re-tratamiento de pacientes con hepatitis crónica C genotipo 1, no respondedores al tratamiento con Peg-IFN/RBV, mediante triple terapia añadiendo a los mismos antivirales 200 mg/día de talidomida. Resultados: ninguno de los once pacientes que fueron incluidos en el ensayo consiguió respuesta viral completa en la semana 12 ni respuesta viral sostenida. La dinámica viral en las 12 primeras semanas de tratamiento no difirió de la dinámica viral durante el primer curso de tratamiento. La triple terapia fue bien tolerada y solo un paciente desarrolló neuropatía bilateral autolimitada. Conclusiones: añadir talidomida al tratamiento estándar fue bien tolerado pero no incrementó la tasa de respuesta viral sostenida en pacientes con hepatitis C genotipo 1 no respondedores previos(AU)

Background: fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy. Aims: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. Methods: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study). Results: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. Conclusions: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients(AU)

Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept.

BACKGROUND: fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy. AIMS: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. METHODS: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study). RESULTS: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. CONCLUSIONS: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.