ABSTRACT
Importance: Active immunization for hepatitis B virus (HBV) infection is recommended in patients living with HIV. Limited evidence is available about the most appropriate regimen of HBV vaccination among those who have not responded to an initial schedule. Objective: To determine the efficacy of a high-dose schedule compared with a standard dose of HBV vaccination. Design, Setting, and Participants: This double-masked, parallel-group, randomized controlled trial included patients living with HIV at a single outpatient HIV and hepatology clinic in Chile for whom previous HBV vaccination had failed. Patients with hepatitis B surface antibody (anti-HBs) titers less than 10 IU/L after an initial HBV vaccination regimen were included. Consecutive patients were recruited between December 2013 and March 2018. Data were analyzed in June 2018 using intention-to-treat analysis. Intervention: The high-dose HBV vaccination group consisted of 3 doses of 40 µg recombinant hepatitis B vaccine at 0, 1, and 2 months. The standard-dose group received 3 doses 20 µg each at 0, 1, and 2 months. Main Outcomes and Measures: Primary outcome was the serologic response to HBV vaccination (anti-HBs greater than 10 IU/L) 4 to 8 weeks after completion of the schedule. Secondary outcomes were anti-HBs greater than 100 IU/L and seroprotective anti-HBs at 1 year follow up. Results: A total of 107 patients underwent randomization (55 to the standard-dose group, 52 to the high-dose group); 81 (75.7%) were men, and the mean (SD) patient age was 47.0 (13.3) years. Nearly all patients were receiving antiretroviral therapy (105 patients [98%]) and 92 patients (86%) had an undetectable HIV viral load. Mean (SD) CD4 count was 418 (205) cells/mm3. There were no differences in baseline characteristics between groups. Serological response in the high-dose group was found in 36 of 50 patients (72%; 95% CI, 56.9%-82.9%) compared with 28 of 55 patients in the standard-dose group (51%; 95% CI, 37.1%-64.6%) (odds ratio, 2.48; 95% CI, 1.02-6.10; P = .03). Mean (SD) anti-HB levels were 398.0 (433.4) IU/L in the high-dose group and 158.5 (301.4) IU/L in the standard-dose group (P < .001). Of patients with a serological response in the high-dose group, 29 of 36 (80.6%) had anti-HBs titers greater than 100 IU/L compared with 14 of 28 responders (50.0%) in the standard-dose group (P = .02). At 1-year follow-up, 20 of 25 patients (80.0%) with a serological response in the high-dose group had protective anti-HBs vs 9 of 23 patients (39.1%) in the standard-dose group (P = .01). Conclusions and Relevance: The results of this randomized clinical trial suggest that use of a high-dose regimen for HBV revaccination for patients with HIV achieves a higher and longer-lasting serological response as compared with a standard-dose regimen. Trial Registration: ClinicalTrials.gov Identifier: NCT02003703.
Subject(s)
HIV Infections/complications , Hepatitis B Vaccines/administration & dosage , Hepatitis B/prevention & control , Immunization, Secondary/methods , Chile , Double-Blind Method , Female , Hepatitis B/immunology , Humans , Immunization Schedule , Intention to Treat Analysis , Male , Middle AgedABSTRACT
INTRODUCTION: Invasive fungal diseases (IFD) by filamentous fungi are a common cause of morbidity and mortality in immunocompromised patients, especially those with myeloid leukemia. In 2011 a protocol for the rapid diagnosis of IFD by filamentous fungi was implemented in Valparaiso Region. OBJECTIVES: To describe cases of IFD by filamentous fungi of the Valparaíso Region, since the implementation of rapid diagnosis and to compare results with the period 2004-2009. MATERIALS AND METHOD: Descriptive and prospective study conducted in two public hospitals: Carlos van Buren at Valparaiso and Gustavo Fricke at Viña del Mar. We selected patients with a diagnosis of filamentous fungal diseases considering the EORTC/MSG criteria. Demographics, underlying diseases, risk factors for EFI, galactomannan (GM) results in blood and bronchoalveolar lavage, cultures and biopsies, treatment and overall lethality rates at 30 days were registered. RESULTS: Eighteen patients were detected, 6 with proven and 12 probable IFD. Nine were diagnosed by GM, 8 by culture and two with both methods. In cases which the agent (9/18) was isolated from Rhizopus oryzae was the most frequent. When comparing overall lethality with the period 2004-2009, there was a reduction of 47.8%, which was statistically significant. CONCLUSIONS: Compared to data previously published in the region, demographic and comorbidities of patients with IFD caused by filamentous fungi are similar, however the currently rapid diagnosis protocol has improved survival of patients and lethality experienced overall decrease.
Subject(s)
Fungi/classification , Mycoses/diagnosis , Chile , Female , Humans , Immunocompromised Host , Male , Mycoses/microbiology , Mycoses/mortality , Prospective Studies , Reagent Kits, DiagnosticABSTRACT
Introduction: Invasive fungal diseases (IFD) by filamentous fungi are a common cause of morbidity and mortality in immunocompromised patients, especially those with myeloid leukemia. In 2011 a protocol for the rapid diagnosis of IFD by filamentous fungi was implemented in Valparaiso Region. Objectives: To describe cases of IFD by filamentous fungi of the Valparaíso Region, since the implementation of rapid diagnosis and to compare results with the period 2004-2009. Materials and Method: Descriptive and prospective study conducted in two public hospitals: Carlos van Buren at Valparaiso and Gustavo Fricke at Viña del Mar. We selected patients with a diagnosis of filamentous fungal diseases considering the EORTC/MSG criteria. Demographics, underlying diseases, risk factors for EFI, galactomannan (GM) results in blood and bronchoalveolar lavage, cultures and biopsies, treatment and overall lethality rates at 30 days were registered. Results: Eighteen patients were detected, 6 with proven and 12 probable IFD. Nine were diagnosed by GM, 8 by culture and two with both methods. In cases which the agent (9/18) was isolated from Rhizopus oryzae was the most frequent. When comparing overall lethality with the period 2004-2009, there was a reduction of 47.8%, which was statistically significant. Conclusions: Compared to data previously published in the region, demographic and comorbidities of patients with IFD caused by filamentous fungi are similar, however the currently rapid diagnosis protocol has improved survival of patients and lethality experienced overall decrease.
Introducción: la enfermedad fúngica invasora (EFI) por hongos filamentosos es una causa frecuente de morbilidad y mortalidad en pacientes inmunocomprometidos, en especial en aquellos con leucemia mieloide. En el 2011 se implementó en la Región de Valparaíso un protocolo de diagnóstico rápido de la EFI por hongos filamentosos. Objetivos: describir los casos de EFI por hongos filamentosos de la Región de Valparaíso, desde la implementación del diagnóstico rápido y compararlos con el período 2004-2009. Materiales y Método: Estudio descriptivo y prospectivo realizado en los hospitales públicos Carlos van Buren de Valparaíso y Gustavo Fricke de Viña del Mar. Se seleccionaron aquellos pacientes con diagnóstico de EFI por hongos filamentosos considerando los criterios EORTC/MSG. Se obtuvieron datos demográficos, enfermedad de base, factores de riesgo para EFI, resultados de galactomanano (GM), cultivos y biopsias, tratamiento y letalidad global a 30 días. Resultados: Se identificaron 18 pacientes, seis con EFI probadas y 12 probables. Nueve fueron diagnosticados con galactomanano, ocho con cultivos y uno con los dos métodos. En los casos en que se aisló el agente (9/18), Rhizopus oryzae fue el más frecuente. Al comparar la letalidad global con la del período 2004-2009, hubo una reducción de 47,8%, la cual fue estadísticamente significativa. Conclusiones: En relación a lo publicado anteriormente en la región, se conservan las características demográficas y de co-morbilidad de los pacientes con EFI por hongos filamentosos; sin embargo, la introducción del nuevo protocolo de diagnóstico rápido se asoció a una disminución en la letalidad global.
