Impact of interferon-free therapies in HIV/HCV co-infected patients on real clinical practice: results from a multicenter region-wide cohort study (2014-2018).

BACKGROUND: Here, we assess the efficacy and safety of direct antiviral agents (DAAs) in a real-world cohort of co-infected individuals, and evaluate the consistency between clinical practice and guideline recommendations. METHODS: Multicenter, prospective cohort study of HIV/HCV co-infected patients followed-up in nine sites in Spain. All patients with detectable HCV-RNA naive to second-generation DAAs were enrolled. The primary endpoint was the assessment of sustained virological response at week 12 (SVR12). We performed intention-to-treat (ITT), per-protocol (PP), and multivariable analyses to identify factors associated with therapeutic failure. We compared the DAAs we administered to available guideline recommendations. Schemes not perfectly adjusted to the recommendations were defined as sub-optimal. RESULTS: Overall, 316 patients (82.1% male) received a total of 330 treatments. Of these, 43.9% were cirrhotic and 40.6% were treatment-experienced. In the ITT and PP analyses, SVR12 was achieved in 90.9% [95% confidence interval (CI) 87.3-93.6] and 93.7% (95% CI 90.5-95.6), respectively. Only alcohol abuse [odds ratio (OR): 0.33; 95% CI 0.138-0.789, P = 0.013] and a higher basal bilirubin level (OR: 0.595; 95% CI 0.416-0.851, P = 0.004) were independently associated to therapeutic failure. A progressive decrease in the proportion of sub-optimal treatments was observed over time, from 75% in 2014 to 0% in 2018. Being treated with a sub-optimal regimen was not associated with failure. CONCLUSION: Despite numerous difficulties in treatment access and in adaptation to the changing guidelines, we detected no differences among the DAAs used, nor did we detect a lower efficacy when the chosen treatment was not optimal.

Does fibrosis really regress in HIV/hepatitis C virus co-infected patients after treatment with direct antiviral agents?

OBJECTIVE: To evaluate the progression of liver stiffness after treatment with direct antiviral agents (DAAs), to identify predictive factors of fibrosis regression and to analyze the changes of scores AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) after treatment. DESIGN: Multicenter prospective cohort study of HIV/HCV co-infected patients conducted within the GECMEI cohort, Spain. METHODS: Individuals were eligible if they were willing to start DAAs and underwent two transient elastographies: at baseline and after the end of treatment (EOT). All patients with detectable HCV RNA naïve to DAAs were consecutively enrolled from nine medical hospitals. Liver stiffness results were categorized in four Metavir stages (F1: <7.1; F2 : 7.1--9.5; F3 : 9.5--2.4; F4: >12.4 kPa). The APRI and FIB-4 scores were calculated at baseline, EOT and 12 weeks after EOT. RESULTS: One hundred and seventy-eight patients were examined throughout a follow-up of 16.3 months (IQR: 12.5-25). The median of liver stiffness decrease was 2.6 kPa (IQR: 0-6.3). A greater improvement was observed in F3-F4 compared with F1-F2, (6.4 vs. 0.91 kPa, P < 0.001; P = 0.001, respectively). A decline between baseline and EOT measures was observed in APRI and FIB-4 (P < 0.001). Sustained virological response (SVR12) achievement was the only predictor of fibrosis regression [OR:17.4 (95% CI: 1.8-164.6; P = 0.013)]. CONCLUSION: Most patients experienced a significant reduction of liver stiffness and APRI and FIB-4 scores. This improvement was greater in those with advanced liver disease. SVR12 was the only predictor of fibrosis regression. The significance of this reduction is unclear and could reflect a decline in inflammation rather than true fibrosis regression.

Efectividad del tratamiento con agentes antivirales directos en pacientes con coinfección por VHC y VIH. Estudio de cohorte multicéntrico / Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study

Introducción: la eficacia de los agentes antivirales directos (AAD) ha quedado demostrada en ensayos clínicos tanto en mono como en coinfectados. Nuestro objetivo es analizar la efectividad y toxicidad de este tratamiento en vida real en pacientes con coinfección por VIH y VHC así como determinar variables asociadas a una evolución desfavorable. Métodos: estudio ambispectivo multicéntrico en una cohorte de pacientes coinfectados. Los datos fueron recogidos en ocho centros de Castilla-La Mancha entre 2014 y 2016. Se realizó un análisis por intención de tratamiento en el que cualquier pérdida de seguimiento, abandono de tratamiento o toxicidad terapéutica se consideró fracaso. Resultados: se estudiaron 229 pacientes con una mediana de edad de 49,6 años con predominio masculino (83%). Menos de un 10% presentaba carga viral (CV) detectable para el VIH. El genotipo de VHC más prevalente fue el 1 (65,1%). Un 50% tenía hepatopatía en grado de cirrosis. El 65% presentaba más de 800.000 copias/ml de CV de VHC. La respuesta viral sostenida (RVS) se alcanzó globalmente en el 91,7%. La estrategia de AAD más utilizada fue sofosbuvir/ ledipasvir. Un 52% de las pautas incluyeron ribavirina. El 65,9% completó pautas de 12 semanas y un 30%, de 24 semanas. Hubo 19 fracasos terapéuticos. No existen diferencias entre las distintas estrategias de AAD utilizadas. No se observó ningún factor predictor independiente de RVS. Conclusiones: el tratamiento del VHC en pacientes coinfectados presenta tasas de RVS muy elevadas también en vida real. La toxicidad es excepcional. No hemos identificado factores predictores específicos de evolución desfavorable (AU)

ntroduction: The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. Methods: This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. Results: A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. Conclusions: HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome (AU)

Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study.

INTRODUCTION: The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. METHODS: This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. RESULTS: A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. CONCLUSIONS: HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome.

Síndrome de Paget-Schroetter / Paget-Schroetter syndrome

No disponible

[Incidence of pneumonia in HIV-infected patients in the highly active antiretroviral therapy era]. / Incidencia de neumonía en pacientes infectados por el virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividad.

BACKGROUND AND OBJECTIVE: There is scant data comparing the incidence of pneumonia in the community and in the human immunodeficiency virus (HIV) population in highly active antiretroviral therapy (HAART) era. PATIENTS AND METHOD: Prospective study during 18 months. Data were obtained by the means of the electronic clinical record. Incidence rate was compared between HIV positive and negative patients. RESULTS: There were 529 pneumonia episodes in global population (n = 220,000), 1.6 cases/1000 person-year. HIV-infected patients (n = 170) suffered 12 episodes of pneumonia; 46 cases/1000 person-year (relative risk = 29.3, 95% confidence interval, 16.34-51.4; p < 0.01). HIV infected patients with pneumonia have a lower CD4 count (mean 434 versus 230 cells/ml; p = 0.04), higher viral load (4.1 versus 3.2 log copies/ml; p = 0.07) and received antiretroviral treatment in a similar proportion compared to HIV without pneumonia (62 versus a 66.7%, p = 0.5). CONCLUSIONS: Pneumonia in HIV infected patients may be about 30 times more frequent than general population in HAART era. Prevention measures should be reinforced.

Incidencia de neumonía en pacientes infectados por el virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividad / Incidence of pneumonia in HIV-infected patients in the highly active antiretroviral therapy era

Fundamento y objetivo: Apenas hay datos sobre la incidencia de neumonía en los pacientes infectados por el virus de la inmunodeficiencia humana (VIH) respecto a la población general en la era del tratamiento antirretroviral de gran actividad (TARGA). Pacientes y método: Se ha realizado un registro prospectivo de las neumonías atendidas en un hospital de zona durante 18 meses. Se comparan las tasas de incidencia entre la población general y los pacientes infectados por el VIH. Resultados: En la población general (n = 220.000) la incidencia de neumonía fue de 1,6 casos/1.000 personas/año, frente a 46 casos/ 1.000 personas/año en pacientes infectados por el VIH (n = 170) (riesgo relativo = 29,3; intervalo de confianza del 95%, 16,34-51,4; p < 0,01). Los pacientes seropositivos con neumonía tenían una cifra inferior de linfocitos CD4 (media de 434 frente a 230 células/ml; p = 0,04), una carga viral más elevada (4,1 frente a 3,2 log copias/ml; p = 0,07) y recibían TARGA en un porcentaje similar a los que no presentaron neumonía (el 62 frente al 66,7%; p = 0,5). Conclusiones: En la era del TARGA, la incidencia de neumonía en la población infectada por el VIH puede ser unas 30 veces superior a la de la población general, por lo que es necesario reforzar las medidas de prevención en este tipo de pacientes

Background and objective: There is scant data comparing the incidence of pneumonia in the community and in the human immunodeficiency virus (HIV) population in highly active antiretroviral therapy (HAART) era. Patients and method: Prospective study during 18 months. Data were obtained by the means of the electronic clinical record. Incidence rate was compared between HIV positive and negative patients. Results: There were 529 pneumonia episodes in global population (n = 220,000), 1.6 cases/1000 person-year. HIV-infected patients (n = 170) suffered 12 episodes of pneumonia; 46 cases/1000 person-year (relative risk = 29.3, 95% confidence interval, 16.34-51.4; p < 0.01). HIV infected patients with pneumonia have a lower CD4 count (mean 434 versus 230 cells/ml; p = 0.04), higher viral load (4.1 versus 3.2 log copies/ml; p = 0.07) and received antiretroviral treatment in a similar proportion compared to HIV without pneumonia (62 versus a 66.7%, p = 0.5). Conclusions: Pneumonia in HIV infected patients may be about 30 times more frequent than general population in HAART era. Prevention measures should be reinforced

Decisiones al final de la vida: suspensión de antibióticos en presencia de infección activa / End-of-life decisions: foregoing antibiotic therapy in patients with an active infection

La limitación de esfuerzos terapéuticos es una medida escasamente evaluada en nuestro medio. Se valoran las características de los pacientes en los que se retiran los antibióticos en presencia de una infección activa. Se recogieron datos de todos los pacientes ancianos ingresados consecutivamente en medicina interna con infección activa a los que se les suspendía el antibiótico. Se compararon las características de los pacientes que fallecieron y de los que no. En el estudio se incluyó a 63 pacientes (8,9% de los ingresos); 84,6 ± 9,1 años. Un 86% tenía demencia, un 73%, incapacidad, y un 30%, neoplasia activa. El motivo de la retirada de los antibióticos fue siempre la percepción de una muerte cercana y/o la falta de respuesta al tratamiento. La mortalidad fue del 89%. Entre los que fallecieron, predominó el sexo femenino (el 95 frente al 76%) y tanto el tiempo sin antibiótico (2,9 frente a 8,5 días) como la estancia media (9,6 frente a 16,0 días) fueron más breves (p < 0,05). La suspensión del antibiótico es una medida no infrecuente en nuestro medio y está concentrada en pacientes con mal pronóstico vital y mala situación previa

Limitation of therapy has been little studied in our environment. Data were gathered on all patients with active infection consecutively admitted to the internal medicine department of our hospital in whom antibiotic therapy was withdrawn or withheld. The characteristics of patients who died and those of patients who survived were compared. A total of 63 patients (8.9% of admissions) were included; the mean age was 84.6 years ± 9.1. Dementia was present in 86%, incapacity in 73% and neoplasms in 30%. In all patients, the reason for withdrawing or withholding antibiotic treatment was the perception of impending death and/or lack of response to active treatment. In all patients, the families were involved in the decision to forego treatment. Mortality was 89%. Female sex was more common (95% versus 76%) and length of stay (9.6 versus 16.0 days) and time without antibiotic treatment (2.9 versus 8.5 days) were shorter in patients who died than in the group who survived. The decision to forego antibiotic treatment is not infrequent in our hospital. Most patients were elderly, had diseases with poor vital prognosis, and showed poor prior health status