Impact of the implementation of a Sepsis Code Program in medical patient management: a cohort study in an Internal Medicine ward / Impacto de la implementación del Programa Código Sepsis en una planta de hospitalización médica: estudio de una cohorte de pacientes de Medicina Interna

Introduction. Sepsis is the main cause of death in hospitals and the implementation of diagnosis and treatment bundles has shown to improve its evolution. However, there is alack of evidence about patients attended in conventional units.Methods. A 3-year retrospective cohort study was conducted. Patients hospitalized in Internal Medicine units withsepsis were included and assigned to two cohorts according toSepsis Code (SC) activation (group A) or not (B). Baseline andevolution variables were collected.Results. A total of 653 patients were included. In 296 cases SC was activated. Mean age was 81.43 years, median Charlson comorbidity index (CCI) was 2 and 63.25% showed somefunctional disability. More bundles were completed in group A:blood cultures 95.2% vs 72.5% (p < 0.001), extended spectrumantibiotics 59.1% vs 41.4% (p < 0.001), fluid resuscitation96.62% vs 80.95% (p < 0.001). Infection control at 72 hourswas quite higher in group A (81.42% vs 55.18%, odds ratio3.55 [2.48-5.09]). Antibiotic was optimized more frequently ingroup A (60.77% vs 47.03%, p 0.008). Mean in-hospital staywas 10.63 days (11.44 vs 8.53 days, p < 0.001). Complicationsduring hospitalization appeared in 51.76% of patients, especially in group B (45.95% vs 56.58%, odds ratio 1.53 [1.12-2.09]). Hospital readmissions were higher in group A (40% vs24.76%, p < 0.001). 28-day mortality was significantly lower ingroup A (20.95% vs 42.86%, odds ratio 0.33 [0.23-0.47]).Conclusions. Implementation of SC seems to be effectivein improving short-term outcomes in IM patients, althoughtherapy should be tailored in an individual basis (AU)

Introducción. La sepsis es la principal causa de muerte enlos hospitales y la implantación de códigos para su manejo hademostrado mejorar su evolución. Sin embargo, es escasa laevidencia relativa a los pacientes atendidos en unidades médicas convencionales.Métodos. Se realizó un estudio de cohortes retrospectivode 3 años. Se incluyeron pacientes con sepsis hospitalizados enunidades de Medicina Interna y se asignaron a dos cohortessegún la activación del Código Sepsis (CS) (grupo A) o no (B).Se recogieron variables basales y de evolución.Resultados. Se incluyeron 653 pacientes. En 296 casos seactivó el SC. La edad media fue de 81,43 años, la mediana delíndice de comorbilidad de Charlson (ICC) fue de 2 y el 63,25%presentaba alguna limitación funcional. Se realizaron más acciones diagnósticas y terapéuticas en el grupo A: hemocultivos95,2% vs 72,5% (p < 0,001), antibióticos de espectro extendido59,1% vs 41,4% (p < 0,001), reanimación con líquidos 96,62%vs 80,95% (p < 0,001). El control de la infección a las 72 horasfue superior en el grupo A (81,42% vs 55,18%, odds ratio 3,55[2,48-5,09]). La optimización de los antibióticos fue más frecuente en el grupo A (60,77% vs 47,03%, p 0,008). La estanciamedia en el hospital fue de 10,63 días (11,44 vs 8,53 días, p <0,001). Aparecieron complicaciones durante la hospitalizaciónen el 51,76% de los pacientes, especialmente en el grupo B(45,95% vs 56,58%, odds ratio 1,53 [1,12-2,09]). Los pacientesdel grupo A reingresaron más (40% vs 24,76%, p < 0,001). Lamortalidad a los 28 días fue significativamente menor en elgrupo A (20,95% frente a 42,86%, odds ratio 0,33 [0,23-0,47]). (AU)

Evolution of HCV associated porphyria cutanea tarda after HCV sustained virologic response by direct acting antivirals.

OBJECTIVES: Porphyria cutanea tarda (PCT) is common and usually associated with HCV chronic infection and HFE polymorphisms. Since DAA IFN-free regimens availability, SVR for HCV is nearly a constant and we wonder whether HCV SVR determine PCT evolution. METHODS: Retrospective observational study including patients with HCV associated PCT from the Gastroenterology and Infectious Diseases Departments at our Hospital, treated with DAA (Apr/2015-Apr/2017). Clinical variables of PCT were collected at PCT diagnosis, after PCT treatment, before DAA use and after SVR achievement. UROD activity and C282Y/H63D polymorphisms were registered. SPSS 22.0. RESULTS: 13 HCV-PCT patients included: median age 52.5 years; 4 females; 8 HCV/HIV co-infected (all on undetectable viral load). Classical PCT factors: 12 smoked, 9 alcohol abuse, 6 former IDU. 10 type I PCT and 1 type II PCT. HFE polymorphism: 2 cases with C282Y/H63D; H63D polymorphism in 8. PCT manifestations resolved with PCT treatment in 4 patients, almost completely in 7 patients, 1 patient referred stabilization and one worsened. After DAA treatment all the residual lesions resolved, what always led to specific treatment interruption. CONCLUSIONS: Our series of cases of HCV-associated PCT shows that SVR after DAA treatment leads to PCT resolution. Porphyrin levels are not needed after ending PCT specific treatment interruption when there are no residual skin lesions in HCV-associated PCT.

Dynamics of creatinine estimated glomerular filtration rate using one or more antiretrovirals that inhibit creatinine tubular secretion.

BACKGROUND: Cobicistat, dolutegravir and rilpivirine are all modest inhibitors of proximal tubular creatinine secretion (IPTCrS) and hence a moderate and early non-progressive creatinine estimated glomerular filtration rate (Cr-eGFR) reduction has been observed in clinical trials. Data regarding the impact of combination of those drugs on Cr-eGFR, in the clinical practice, are scarcely known. METHODS: Changes in Cr-eGFR after starting darunavir/cobicistat alone or in combination with dolutegravir and/or rilpivirine were studied in a nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat. The relationship between Cr-eGFR changes over time and the use of darunavir/cobicistat alone or darunavir/cobicistat plus dolutegravir and/or rilpivirine adjusted by different HIV patient's characteristics, socio-demographics, HIV severity and use of tenofovir concomitant medication other than antiretrovirals was explored through univariate and multivariate analyses. RESULTS: The analysis included 725 patients. At 48 weeks, the combination of two or more IPTCrS (darunavir/cobicistat with rilpivirine and/or dolutegravir) was associated with higher decreases in Cr-eGFR [adjusted median difference (±SD) -3.5 ± 1.6 (95% CI -6.6 to -0.3), P = 0.047], and a decrease up to or higher than 15 mL/min/1.73 m2 was more frequent [adjusted OR 3.233 (95% CI 1.343-7.782), P = 0.009], with respect to darunavir/cobicistat alone. The Cr-eGFR changes between darunavir/cobicistat and darunavir/cobicistat with rilpivirine and/or dolutegravir showed more significant decreases in patients taking two or more IPTCrS at 12, 24 and 48 weeks. (ClinicalTrials.gov: NCT03042390). CONCLUSIONS: Concomitant use of darunavir/cobicistat plus IPTCrS dolutegravir, rilpivirine, or both produced an additive effect in the expected Cr-eGFR decrease.

Ambulatory Blood Pressure Monitoring in HIV-Infected Patients: Usefulness for Cardiovascular Risk Assessment.

BACKGROUND: There is a lack of consensus regarding the risk of hypertension in HIV-infected patients compared to the general population. Ambulatory blood pressure monitoring (ABPM) is the most accurate method for the hypertension diagnosis. Nevertheless, it is rarely used in HIV clinical care. MATERIALS AND METHODS: All HIV-infected patients who underwent 24 hours ABPM were included. The agreement between office blood pressure (BP) readings and ABPM was analyzed. The rate of patients with masked hypertension (MH), isolated clinical hypertension, and nocturnal hypertension was obtained. Furthermore, it was analyzed if the differences between both methods may affect the cardiovascular risk (CVR) assessment. RESULTS: A total of 116 patients were included. The κ coefficient between office BP and ABPM was 0.248. Over a quarter of the cohort was diagnosed with MH-25.8% (CI 95% 17.7%-34.0%), and 12% (CI 95%: 6.1%-16.1%) was diagnosed with ICH. Moreover, 19% of patients had hypertension exclusively during the night. The patients classified as low risk according to the CVR scores had a different diagnosis with ABPM than with office BP (P < .001). CONCLUSIONS: The agreement between office BP and ABPM was low in HIV-infected patients. Ambulatory BP monitoring is useful in HIV-infected patients as a hypertension diagnosis method, especially among patients classified as low risk.

Higher relapse rate among HIV/HCV-coinfected patients receiving sofosbuvir/ledipasvir for 8 vs 12 weeks.

OBJECTIVES: To compare the efficacy of sofosbuvir/ledipasvir (SOF/LDV) for 8 weeks (SL8) versus a 12-week course of SOF/LDV (SL12) among HIV/HCV-coinfected patients in clinical practice. In addition we compared sustained virological response (SVR) rates achieved with SL8 in HCV-monoinfected and HIV/HCV-coinfected patients in a real life setting. METHODS: HCV-infected patients were retrospectively selected from the HEPAVIR-DAA and GEHEP-MONO real-life prospective cohorts if they fulfilled the following criteria: 1) Infected with genotype 1; 2) Treatment with SL8 or SL12; 3) Treatment naïve prior to receiving SL8 or SL12; 4) Absence of cirrhosis; 5) Baseline HCV RNA<6 × 106 IU/mL; 6) Reached the scheduled time-point for SVR (SVR12) assessment. SVR12 and relapse rates of HCV-monoinfected and HIV/HCV-coinfected patients were compared on an intention to treat basis. The responses with SL8 and SL12 were also compared. RESULTS: In the SL8 group, 107 (51%) HCV-monoinfected and 102 (49%) HIV/HCV-coinfected patients were included. One hundred and sixty-four (43%) HCV-monoinfected subjects and 220 (57%) HIV/HCV-coinfected patients received SL12. SVR12 rates for HIV/HCV-coinfected patients treated with SL8 vs SL12 were SVR12 92.2% vs. 97.3% (p = 0.044) and the respective relapse rates were 4.9% vs. 0.5% (p = 0.013). SVR12 rates for SL8 among HCV-monoinfected and HIV/HCV-coinfected patients were: 96.3% vs. 92.2% (p = 0.243), respectively. The corresponding relapse rates were 0.9% vs. 4.9% (p = 0.112). CONCLUSION: HIV/HCV-coinfected patients reach high rates of SVR12 with SL8, although lower than with SL12, mainly due to a higher probability of relapse. SVR12 rates with SL8 are numerically lower and the proportion of relapses higher in HIV/HCVcoinfected patients than in HCV-monoinfected subjects.

HIV-coinfected patients respond worse to direct-acting antiviral-based therapy against chronic hepatitis C in real life than HCV-monoinfected individuals: a prospective cohort study.

OBJECTIVE: HIV/HCV-coinfected patients and hepatitis C virus (HCV) monoinfected subjects are thought to respond equally to direct-acting antiviral (DAA)-based therapy despite the lack of data derived from clinical trials. This study is aimed to evaluate the impact of HIV coinfection on the response to DAA-based treatment against HCV infection in the clinical practice. PATIENTS AND METHODS: In a prospective multicohort study, patients who initiated DAA-based therapy at the Infectious Disease Units of 33 hospitals throughout Spain were included. The primary efficacy outcome variables were the achievement of sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12). RESULTS: A total of 908 individuals had reached the SVR12 evaluation time-point, 426 (46.9%) were HIV/HCV-coinfected, and 472 (52%) received interferon (IFN)-free therapy. In an intention-to-treat analysis, SVR12 rates in subjects with and without HIV-coinfection were 55.3% (94/170 patients) versus 67.3% (179/266 subjects; p = 0.012) for IFN-based treatment and 86.3% (221/256 subjects) versus 94.9% (205/216 patients, p = 0.002) for IFN-free regimens. Relapse after end-of-treatment response to IFN-free therapy was observed in 3/208 (1.4%) HCV-monoinfected subjects and 10/231 (4.4%) HIV/HCV-coinfected individuals (p = 0.075). In a multivariate analysis adjusted for age, sex, transmission route, body-mass index, HCV genotype, and cirrhosis, the absence of HIV-coinfection (adjusted odds ratio: 3.367; 95% confidence interval: 1.15-9.854; p = 0.027) was independently associated with SVR12 to IFN-free therapy. CONCLUSIONS: HIV-coinfection is associated with worse response to DAA-based therapy against HCV infection. In patients receiving IFN-free therapy, this fact seems to be mainly driven by a higher rate of relapses among HIV-coinfected subjects.

Prevalencia y características de los pacientes con infección por virus de la inmunodeficiencia humana (VIH) diagnosticados de novo en un servicio de urgencias / Prevalence of undiagnosed human immunodeficiency virus infection in an emergency department and the characteristics of newly diagnosed patients

Objetivo: Estimar la prevalencia de la infección por el virus de la inmunodeficiencia humana (VIH) no diagnosticada entre la población que acude al servicio de urgencias hospitalario (SUH) mediante la realización rutinaria del test para VIH, y describir los factores asociados al diagnóstico. Método: Estudio descriptivo transversal que incluyó a los pacientes entre 15 y 75 años valorados en la zona de pacientes ambulantes del SUH y a los que se les realizó una analítica sanguínea por su motivo de consulta, en la que se obtuvo una muestra para realizar la prueba del VIH de manera rutinaria mediante test de enzimoinmunoanálisis (EIA) de 4ª generación. Los pacientes con resultado positivo fueron remitidos al servicio de infecciosas para seguimiento y tratamiento. Resultados: Se obtuvieron muestras de sangre de 1.722 pacientes. De estos, 21 (1,2%) rechazaron la realización de la serología y 19 (1,1%) no fueron finalmente analizados. La prevalencia de infección VIH no diagnosticada entre los 1.682 pacientes analizados fue del 0,6% [IC 95%: 0,23-0,96%]. Fue, sin significación estadística, mayor en los pacientes nacidos en otros países 0,97% [IC 95%: 0,3-2,20] y en los pacientes de 36 a 50 años 1,46% [IC 95%: 0,4-2,5]. Los factores que se asociaron con infección no conocida por VIH fueron ser hombre [OR: 5,78 (IC 95%: 1,0-31,4)], tener un motivo de consulta sugerente de infección [OR: 8,14 (IC 95%: 1,6-41,4)] y tener antecedentes de hepatitis [OR: 5,53 (IC 95%: 1,1-27,7)]. Conclusión: Hubo una alta prevalencia (0,6%) de infección por VIH no diagnosticada entre los pacientes atendidos en urgencias, los cuales mostraron una alta aceptación para realizar una serología VIH de manera rutinaria y universal. Estos resultados aconsejan mejorar las estrategias de detección de infección oculta por VIH (AU)

Objective: To estimate the prevalence of undiagnosed human immunodeficiency virus (HIV) infection detected by routine testing of patients seeking care in an emergency department and to describe the characteristics associated with new HIV-infection diagnosis. Methods: Walk-in patients between the ages of 15 and 75 years who required a blood test were included. Routine fourth-generation enzyme-linked immunoassays were performed to detect HIV infection in all samples extracted. Patients with positive results were referred to the infectious diseases department for monitoring and treatment. Results: Blood samples for 1722 patients were analyzed. Twenty-one patients (1.2%) refused to allow their samples to be tested; 19 more samples (1.1%) could not be tested. The prevalence of undiagnosed HIV infection among the remaining 1682 remaining patients was 0.6% (95% CI, 0.23%–0.96%). The prevalence tended to be nonsignificantly higher among patients born outside Spain (0.97% [95% CI, 0.3%–2.20%]) and in 36–50-year-olds (1.46% [95% CI, 0.4%–2.5%]). Characteristics associated with undiagnosed HIV infection were male sex (odds ratio [OR], 5.78 [95% CI, 1.0–31.4]), presenting with a chief complaint that suggested infection (OR, 8.14 [95% CI, 1.6–41.4]), and a history of hepatitis (OR, 5.53 [95% CI, 1.1–27.7]). Conclusions: The prevalence of undiagnosed HIV infection in our emergency department was high at 0.6%. The rate of patient acceptance of routine HIV testing was high. Strategies that target improving the detection of undiagnosed HIV infection are advisable (AU)

[Prevalence of undiagnosed human immunodeficiency virus infection in an emergency department and the characteristics of newly diagnosed patients]. / Prevalencia y características de los pacientes con infección por virus de la inmunodeficiencia humana (VIH) diagnosticados de novo en un servicio de urgencias.

OBJECTIVES: To estimate the prevalence of undiagnosed human immunodeficiency virus (HIV) infection detected by routine testing of patients seeking care in an emergency department and to describe the characteristics associated with new HIV-infection diagnosis. MATERIAL AND METHODS: Walk-in patients between the ages of 15 and 75 years who required a blood test were included. Routine fourth-generation enzyme-linked immunoassays were performed to detect HIV infection in all samples extracted. Patients with positive results were referred to the infectious diseases department for monitoring and treatment. RESULTS: Blood samples for 1722 patients were analyzed. Twenty-one patients (1.2%) refused to allow their samples to be tested; 19 more samples (1.1%) could not be tested. The prevalence of undiagnosed HIV infection among the remaining 1682 remaining patients was 0.6% (95% CI, 0.23%-0.96%). The prevalence tended to be nonsignificantly higher among patients born outside Spain (0.97% [95% CI, 0.3%-2.20%]) and in 36-50-year-olds (1.46% [95% CI, 0.4%-2.5%]). Characteristics associated with undiagnosed HIV infection were male sex (odds ratio [OR], 5.78 [95% CI, 1.0-31.4]), presenting with a chief complaint that suggested infection (OR, 8.14 [95% CI, 1.6-41.4]), and a history of hepatitis (OR, 5.53 [95% CI, 1.1-27.7]). CONCLUSION: The prevalence of undiagnosed HIV infection in our emergency department was high at 0.6%. The rate of patient acceptance of routine HIV testing was high. Strategies that target improving the detection of undiagnosed HIV infection are advisable.

OBJETIVO: Estimar la prevalencia de la infección por el virus de la inmunodeficiencia humana (VIH) no diagnosticada entre la población que acude al servicio de urgencias hospitalario (SUH) mediante la realización rutinaria del test para VIH, y describir los factores asociados al diagnóstico. METODO: Estudio descriptivo transversal que incluyó a los pacientes entre 15 y 75 años valorados en la zona de pacientes ambulantes del SUH y a los que se les realizó una analítica sanguínea por su motivo de consulta, en la que se obtuvo una muestra para realizar la prueba del VIH de manera rutinaria mediante test de enzimoinmunoanálisis (EIA) de 4ª generación. Los pacientes con resultado positivo fueron remitidos al servicio de infecciosas para seguimiento y tratamiento. RESULTADOS: Se obtuvieron muestras de sangre de 1.722 pacientes. De estos, 21 (1,2%) rechazaron la realización de la serología y 19 (1,1%) no fueron finalmente analizados. La prevalencia de infección VIH no diagnosticada entre los 1.682 pacientes analizados fue del 0,6% [IC 95%: 0,23-0,96%]. Fue, sin significación estadística, mayor en los pacientes nacidos en otros países 0,97% [IC 95%: 0,3-2,20] y en los pacientes de 36 a 50 años 1,46% [IC 95%: 0,4-2,5]. Los factores que se asociaron con infección no conocida por VIH fueron ser hombre [OR: 5,78 (IC 95%: 1,0-31,4)], tener un motivo de consulta sugerente de infección [OR: 8,14 (IC 95%: 1,6-41,4)] y tener antecedentes de hepatitis [OR: 5,53 (IC 95%: 1,1-27,7)]. CONCLUSIONES: Hubo una alta prevalencia (0,6%) de infección por VIH no diagnosticada entre los pacientes atendidos en urgencias, los cuales mostraron una alta aceptación para realizar una serología VIH de manera rutinaria y universal. Estos resultados aconsejan mejorar las estrategias de detección de infección oculta por VIH.

Barreras para el inicio del tratamiento antirretroviral en pacientes con virus de la inmunodeficiencia humana e indicación de tratamiento en España. ¿Por qué no inician tratamiento quienes lo tienen indicado? Estudio Bridgap / Barriers to ART initiation in HIV infected subjects and with treatment indication in Spain. Why don’t they start their treatment? Bridgap Study

INTRODUCCIÓN: En España algunos pacientes con VIH no reciben tratamiento antirretroviral (TAR), aun teniendo indicaciones para ello. Nuestro objetivo es identificar las barreras de inicio del TAR en pacientes con indicación para recibirlo. MÉTODOS: Encuesta transversal en 19 hospitales en España en 2012, incluyendo todos los pacientes que no recibían tratamiento y tenían al menos una indicación según las recomendaciones de Gesida/2011. Las posibles barreras se agruparon así (categorías no excluyentes): a) el médico considera que la indicación no es absoluta; b) el paciente no quiere iniciarlo; c) el médico considera que debe iniciarlo pero existe alguna limitación o contraindicación; y d) el paciente tiene viremia indetectable en ausencia de tratamiento. RESULTADOS: Se incluyeron 256 pacientes de los 784 programados; 84% hombres, mediana de edad 39 años; 57% homosexuales, 24% heterosexuales, 16% UDI. Mediana de tiempo desde el diagnóstico: 3 años, CD4: 501 células/mm3, carga viral 4,4 log. Indicaciones de TAR más frecuentes: CD4 < 500 células/mm3(48%), pareja sexual no infectada (28%), coinfección con virus de la hepatitis C (23%). Las barreras para el inicio del TAR fueron dependientes del médico en el 55% de los casos, del paciente en el 28%, otras limitaciones: 23%, viremia indetectable: 6%. CONCLUSIONES: La mayoría de los pacientes con indicación de TAR lo estaban recibiendo. El motivo más frecuente en quienes no lo recibían fue que el médico pensaba que la indicación no era absoluta, y prefería esperar, lo que sugiere la necesidad de enfatizar en los beneficios de iniciar el TAR en estos casos

INTRODUCTION: In Spain, HIV treatment guidelines are well known and generally followed. However, in some patients there are no plans to initiate ART despite having treatment indications. The current barriers to ART initiation are presented. METHODS: A cross-sectional survey including every HIV infected patient in care in 19 hospitals across Spain in 2012, with ≥1 indication to start ART according to 2011 national treatment guidelines, who had not been scheduled for ART initiation. Reasons for deferring treatment were categorized as follows (non-exclusive categories): a) The physician thinks the indication is not absolute and prefers to defer it; b) The patient does not want to start it; c) The physician thinks ART must be started, but there is some limitation to starting it, and d) The patient has undetectable viral load in absence of ART. RESULTS: A total of 256 patients, out of 784 originally planned, were included. The large majority (84%) were male, median age 39 years, 57% MSM, 24% heterosexuals, and 16% IDUs. Median time since HIV diagnosis was 3 years, median CD4 count, 501 cells/mm3, median viral load 4.4 log copies/ml. Main ART indications were: CD4 count < 500 cells/mm3, 48%; having an uninfected sexual partner, 28%, and hepatitis C coinfection, 23%. Barriers due to, the physician, 55%; the patient, 28%; other limitations, 23%; and undetectable viral load, 6%. CONCLUSIONS: The majority of subjects with ART indication were on it. The most frequent barriers among those who did not receive it were physician-related, suggesting that the relevance of the conditions that indicate ART may need reinforcing

Boceprevir or Telaprevir Based Triple Therapy against Chronic Hepatitis C in HIV Coinfection: Real-Life Safety and Efficacy.

BACKGROUND AND AIMS: Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. METHODS: In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. RESULTS: Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. CONCLUSION: The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable.

[Barriers to ART initiation in HIV infected subjects and with treatment indication in Spain. Why don't they start their treatment? Bridgap Study]. / Barreras para el inicio del tratamiento antirretroviral en pacientes con virus de la inmunodeficiencia humana e indicación de tratamiento en España. ¿Por qué no inician tratamiento quienes lo tienen indicado? Estudio Bridgap.

INTRODUCTION: In Spain, HIV treatment guidelines are well known and generally followed. However, in some patients there are no plans to initiate ART despite having treatment indications. The current barriers to ART initiation are presented. METHODS: A cross-sectional survey including every HIV infected patient in care in 19 hospitals across Spain in 2012, with ≥1 indication to start ART according to 2011 national treatment guidelines, who had not been scheduled for ART initiation. Reasons for deferring treatment were categorized as follows (non-exclusive categories): a) The physician thinks the indication is not absolute and prefers to defer it; b) The patient does not want to start it; c) The physician thinks ART must be started, but there is some limitation to starting it, and d) The patient has undetectable viral load in absence of ART. RESULTS: A total of 256 patients, out of 784 originally planned, were included. The large majority (84%) were male, median age 39 years, 57% MSM, 24% heterosexuals, and 16% IDUs. Median time since HIV diagnosis was 3 years, median CD4 count, 501 cells/mm3, median viral load 4.4 log copies/ml. Main ART indications were: CD4 count <500 cells/mm(3), 48%; having an uninfected sexual partner, 28%, and hepatitis C coinfection, 23%. Barriers due to, the physician, 55%; the patient, 28%; other limitations, 23%; and undetectable viral load, 6%. CONCLUSIONS: The majority of subjects with ART indication were on it. The most frequent barriers among those who did not receive it were physician-related, suggesting that the relevance of the conditions that indicate ART may need reinforcing.

Impact of IL28B genotype on first-week response to telaprevir-based therapy in HIV-HCV coinfection.

BACKGROUND: IL28B genotype predicts response to treatment against HCV with pegylated interferon/ribavirin (PR) and impacts on the outcome of therapy including telaprevir (TVR). This study aimed to determine the influence of the favourable IL28B genotype on early viral kinetics during therapy with TVR/PR in HIV-HCV-coinfected patients. METHODS: All HIV-HCV genotype 1 coinfected subjects who received TVR/PR for at least 4 weeks were included from populations prospectively followed in 22 centres throughout Germany, Switzerland and Spain. RESULTS: Of the 129 subjects included, 38 (29.5%) presented with IL28B genotype CC and 94 (72.9%) were treatment-experienced. A total of 96 (73.8%) patients showed undetectable plasma HCV RNA at treatment week (W)4: 30 (78.9%) of the IL28B-CC carriers and 65 (71.4%) of the non-CC carriers (P=0.377). Among treatment-naive patients, proportions of undetectable HCV RNA among IL28B-CC versus non-CC carriers were 8/9 (88.9%) versus 3/9 (33.3%; P=0.016) and 14/17 (82.4%) versus 11/18 (61.1%; P=0.164) at W2 and W4. The decrease of HCV RNA at W2 and W4 was similar among the IL28B carriers. CONCLUSIONS: IL28B genotype does not predict W4 response to TVR/PR in HIV-HCV-coinfected patients, regardless of their treatment history. However, there is evidence of an impact on response during the first weeks in treatment-naive patients.

Hipoacusia neurosensorial de etiología sifilítica en un paciente con infección por virus de la inmunodeficiencia humana / Neurosensory loss hearing of syphilitic etiology in a patient with human immunodeficiency virus infection

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Características de una población co infectada por el VIH y los virus de las hepatitis B y C por medio de los resultados de la elastografía de transición / Characteristics of a cohort of HIV and hepatitis B and C co-infected patients through the results of transition elastography

Antecedentes y objetivos: El tratamiento de las hepatopatías crónicas en los pacientes VIH positivos es de especial importancia y la detección de fibrosis hepática resulta fundamental para la toma de decisiones. Los objetivos son: describir las características de los pacientes con VIH a los que se realizó elastografía detransición (ET) y analizar la prevalencia y la asociación de diversos factores en el subgrupo de pacientes con fibrosis significativa. Pacientes y métodos: Estudio retrospectivo-prospectivo, descriptivo y de un único centro, realizado en un hospital terciario universitario en el período comprendido entre enero de 2007 hasta febrero de 2010, con 240 pacientes con VIH coinfectados por el virus de la hepatitis B (VHB) o C (VHC), a los que se les realizó ET. Resultados: El 35% de los pacientes no tenía fibrosis, 29.5% presentaba fibrosis medianamente significativa, 10.7% mostraba fibrosis significativa y un 24.8% tenía cirrosis. El 93.3% de los pacientes estaba coinfectado por el VHC; el más frecuente fue el genotipo 1. Se ha encontrado relación significativa entre la fibrosis avanzada y la ausencia de respuesta viral sostenida (RVS), cifra de CD4 < 200 células/mm3 y el consumo de alcohol. Conclusiones: Uno de cada 3 pacientes presenta un estadio de fibrosis significativo y cerca de un cuarto del total tiene cirrosis. La fibrosis significativa se asoció con ausencia de RVS, cifras de CD4 < 200 células/mm3 y consumo de alcohol. Es recomendable tratar a un mayor número de pacientes y de manera más temprana y es en este aspecto donde disponer de una prueba como la ET facilita el diagnóstico del grado de fibrosis para indicar el momento del tratamiento...

[Pharmacokinetic interactions]. / Interacciones farmacocinéticas.

Rilpivirine (RPV) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) that has been approved for use in treatment-naïve patients and which has potent antiviral activity. Its adverse effects profile differs from that of first-generation NNRTs. The pharmacological interactions produced by RPV are due to its effects on the CYP450 system; RPV is a substrate and mild inducer of CYP3A4. Moreover, in vitro, RPV inhibits glycoprotein-P. RPV has clinically significant pharmacological interactions, especially with protease inhibitors (except boosted darunavir and lopinavir) and the NNRTIs efavirenz and nevirapine. Coadministration of RPV with drugs that increase gastric pH, such as omeprazole, or those inducing CYP3A4, such as rifampicin, can significantly reduce RPV concentrations and is contraindicated. The concomitant use of RPV with a CYP3A4 inhibitor (such as clarithromycin) can increase RPV concentrations. Administration of PRV with food is recommended to obtain better absorption and adequate plasma values.

Interacciones farmacocinéticas / Pharmacokinetic interactions

Rilpivirina (RPV) es un fármaco perteneciente a la familia de los inhibidores no nucleósidos de la transcriptasa inversa (INNTI), con potente actividad antiviral, aprobado para pacientes naïve, con perfil de efectos secundarios diferente a los INNTI de primera generación. Las interacciones farmacológicas producidas por RPV se deben a su efecto sobre el sistema CYP450, es sustrato de CYP3A4 y ligeramente inductor. Además, in vitro es inhibidor de la glucoproteína-P. RPV presenta interacciones farmacológicas clínicamente significativas, entre las que destacan los inhibidores de la proteasa, a excepción de darunavir y lopinavir potenciados, y los INNTI efavirenz y nevirapina. La toma de RPV junto con fármacos que aumentan el pH gástrico, como omeprazol, o los que inducen el CYP3A4, como rifampicina, puede causar reducciones significativas en las concentraciones de RPV y está contraindicada. El uso concomitante de RPV con un inhibidor del CYP3A4, por ejemplo claritromicina, puede provocar aumento de las concentraciones de RPV. Se recomienda la administración de RPV con alimentos para obtener mejor absorción y valores plasmáticos adecuados

Rilpivirine (RPV) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) that has been approved for use in treatment-naïve patients and which has potent antiviral activity. Its adverse effects profile differs from that of first-generation NNRTs. The pharmacological interactions produced by RPV are due to its effects on the CYP450 system; RPV is a substrate and mild inducer of CYP3A4. Moreover, in vitro, RPV inhibits glycoprotein-P. RPV has clinically significant pharmacological interactions, especially with protease inhibitors (except boosted darunavir and lopinavir) and the NNRTIs efavirenz and nevirapine. Coadministration of RPV with drugs that increase gastric pH, such as omeprazole, or those inducing CYP3A4, such as rifampicin, can significantly reduce RPV concentrations and is contraindicated. The concomitant use of RPV with a CYP3A4 inhibitor (such as clarithromycin) can increase RPV concentrations. Administration of PRV with food is recommended to obtain better absorption and adequate plasma values

Benefits from sustained virologic response to pegylated interferon plus ribavirin in HIV/hepatitis C virus-coinfected patients with compensated cirrhosis.

BACKGROUND: The objective of this study was to determine the impact of sustained virologic response (SVR) to pegylated interferon (peg-IFN) plus ribavirin (RBV) on the incidence of liver-related complications and overall mortality in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS: We included in this prospective cohort study 166 coinfected patients with compensated cirrhosis, who received peg-IFN plus RBV, to assess the time from the starting date of HCV therapy to the first hepatic decompensation and death due to any cause. RESULTS: SVR was observed in 43 (25%) individuals. Two (4.6%) patients with SVR developed liver decompensation vs 33 (26.8%) individuals without SVR (P = .002). The incidence of liver-related complications was 0.89 cases per 100 person-years (95% confidence interval [CI], .11-3.1) in SVR patients and 6.4 cases per 100 person-years (95% CI, 4.5-8.9) in non-SVR patients. Factors independently associated with liver decompensation were non-SVR (hazard ratio [HR], 8.1; 95% CI, 1.08-61.5; P = .042) and MELD score ≥9 at baseline (HR, 2.9; 95% CI, 1.2-7.2; P = .016). Two (4.6%) patients with SVR died due to any cause compared with 22 (17.9%) individuals without SVR (P = .02). MELD score ≥9 (HR, 3.1; 95% CI, 1.3-7.7; P = .011) and non-SVR (HR, 8.0; 95% CI, 1.07-61; P = .043) were independently associated with overall mortality. CONCLUSIONS: The achievement of SVR following peg-IFN plus RBV markedly reduces the incidence of liver-related decompensation and the overall mortality in HIV/HCV-coinfected patients with compensated cirrhosis.

Short communication: atazanavir-based therapy is associated with higher hepatitis C viral load in HIV type 1-infected subjects with untreated hepatitis C.

We assessed the relationship between atazanavir (ATV)-based antiretroviral treatment (ART) and plasma hepatitis C virus (HCV) viral load in a population of HIV/HCV-coinfected patients. HIV/HCV-coinfected patients who received ART based on a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) were included. Patients were stratified by ART drug [ATV/rtv, lopinavir (LPV/rtv), efavirenz (EFV), nevirapine (NVP), and other PIs], HCV genotype (1/4 and 2/3), and IL28B genotype (CC and non-CC). The Kruskal-Wallis test and chi-squared test were used to compare continuous and categorical variables, respectively. Multivariate analysis consisted of a stepwise linear regression analysis. Six hundred and forty-nine HIV/HCV-coinfected patients were included. HCV genotype 1/4 patients who received ATV had higher HCV RNA levels [6.57 (5.9-6.8) log IU/ml] than those who received LPV [6.1 (5.5-6.5) log IU/ml], EFV [6.1 (5.6-6.4) log IU/ml], NVP [5.8 (5.5-5.9) log IU/ml], or other PIs [6.1 (5.7-6.4) log IU/ml] (p=0.014). This association held for the IL28B genotype (CC versus non-CC). The association was not found in patients carrying HCV genotypes 2/3. The linear regression model identified the IL28B genotype and ATV use as independent factors associated with HCV RNA levels. ATV-based therapy may be associated with a higher HCV RNA viral load in HIV/HCV-coinfected patients.

Response to pegylated interferon plus ribavirin among HIV/hepatitis C virus-coinfected patients with compensated liver cirrhosis.

BACKGROUND: The objective of this study was to determine the efficacy of pegylated interferon (peg-IFN) plus ribavirin (RBV) in human immunodeficiency virus (HIV)-infected patients with hepatitis C virus (HCV)-related compensated liver cirrhosis, as well as the predictors of response in these individuals. METHODS: All subjects enrolled in a prospective cohort of 841 HIV/HCV-coinfected patients who received peg-IFN and RBV and who had a liver biopsy or a liver stiffness measurement within the year before starting peg-IFN plus RBV were included in this study. The sustained virologic response (SVR) rate and predictors of SVR response were analyzed. RESULTS: A total of 629 patients were included in this study; 175 (28%) had cirrhosis. In an intention-to-treat analysis, 44 (25%) patients with cirrhosis and 177 (39%) without cirrhosis achieved SVR (P = .001). Among patients with cirrhosis, SVR was observed in 14%, 47%, and 30% of individuals with HCV genotypes 1, 2-3, and 4, respectively. Discontinuation of therapy owing to adverse events was observed in 30 (17%) individuals with cirrhosis and 37 (8%) subjects without cirrhosis (P = .001). CONCLUSIONS: The efficacy of peg-IFN plus RBV among HIV/HCV-coinfected patients with cirrhosis is lower than in those without cirrhosis, although this antiviral combination still leads to a substantial rate of SVR in those carrying HCV genotype 3. A higher rate of discontinuations of HCV therapy due to adverse events among cirrhotic patients could partially explain the differences in the SVR rate between both populations.