Hepatic safety of maraviroc in HIV-1-infected patients with hepatitis C and/or B co-infection. The Maraviroc Cohort Spanish Group.

INTRODUCTION: Limited data is available regarding the hepatic safety of maraviroc in patients co-infected with HIV and HCV and/or HBV. Our objective was to compare the hepatic safety profile and fibrosis progression in HIV-mono-infected patients and co-infected with HCV and/or HBV treated with maraviroc. METHODS: Retrospective multicentre cohort study of HIV-infected patients receiving treatment with a maraviroc-containing regimen in 27 hospitals in Spain. RESULTS: A total of 667 patients were analyzed, of whom 313 were co-infected with HCV (n=282), HBV (n=14), or both (n=17). Maraviroc main indications were salvage therapy (52%) and drug toxicity (20%). Grade 3-4 hypertransaminasaemia (AST/ALT >5 times ULN) per 100 patient-years of maraviroc exposure, was 5.84 (95% CI, 4.04-8.16) and 1.23 (95% CI, 0.56-2.33) in co-infected and HIV-mono-infected patients, respectively (incidence rate ratio, 4.77; 95% CI, 2.35-10.5). However, the degree of aminotransferase abnormalities remained stable throughout the study in both groups, and no significant between-group differences were seen in the cumulative proportion of patients showing an increase in AST/ALT levels greater than 3.5 times baseline levels. No between-group differences were seen in liver fibrosis over time. With a maraviroc median exposure of 20 months (IQR, 12-41), two patients (0.3%) discontinued maraviroc because of grade 4 hepatitis, and other 2 died due to complications associated to end-stage-liver disease. CONCLUSIONS: Maraviroc-containing regimens showed a low incidence of hepatitis in a large Spanish cohort of HIV-infected patients, including more than 300 patients co-infected with HCV and/or HBV. Co-infection did not influence the maximum liver enzyme level or the fibrosis progression throughout the study.

Hepatic safety of maraviroc in HIV-1-infected patients with hepatitis C and/or B co-infection. The Maraviroc Cohort Spanish Group / Seguridad hepática de maraviroc en pacienes coinfectados con VIH y hepatitis C y/o B. Grupo español de la cohorte de Maraviroc

Introduction: Limited data is available regarding the hepatic safety of maraviroc in patients co-infected with HIV and HCV and/or HBV. Our objective was to compare the hepatic safety profile and fibrosis progression in HIV-mono-infected patients and co-infected with HCV and/or HBV treated with maraviroc. Methods: Retrospective multicentre cohort study of HIV-infected patients receiving treatment with a maraviroc-containing regimen in 27 hospitals in Spain. Results: A total of 667 patients were analyzed, of whom 313 were co-infected with HCV (n=282), HBV (n=14), or both (n=17). Maraviroc main indications were salvage therapy (52%) and drug toxicity (20%). Grade 3-4 hypertransaminasaemia (AST/ALT >5 times ULN) per 100 patient-years of maraviroc exposure, was 5.84 (95% CI, 4.04-8.16) and 1.23 (95% CI, 0.56-2.33) in co-infected and HIV-mono-infected patients, respectively (incidence rate ratio, 4.77; 95% CI, 2.35-10.5). However, the degree of aminotransferase abnormalities remained stable throughout the study in both groups, and no significant between-group differences were seen in the cumulative proportion of patients showing an increase in AST/ALT levels greater than 3.5 times baseline levels. No between-group differences were seen in liver fibrosis over time. With a maraviroc median exposure of 20 months (IQR, 12-41), two patients (0.3%) discontinued maraviroc because of grade 4 hepatitis, and other 2 died due to complications associated to end-stage-liver disease. Conclusions: Maraviroc-containing regimens showed a low incidence of hepatitis in a large Spanish cohort of HIV-infected patients, including more than 300 patients co-infected with HCV and/or HBV. Co-infection did not influence the maximum liver enzyme level or the fibrosis progression throughout the study (AU)

Introducción: La seguridad hepática del maraviroc en pacientes coinfectados por VIH y VHC y/o VHB es poco conocida. Nuestro objetivo es comparar el riesgo de hepatitis y la progresión de la fibrosis hepática en pacientes monoinfectados por VIH y coinfectados por VHC y/o VHB, tratados con maraviroc. Métodos: Estudio de cohortes, retrospectivo, en pacientes infectados por VIH, tratados con maraviroc en 27 hospitales españoles. Resultados: Analizamos 667 pacientes, 313 coinfectados por VHC (n=282), VHB (n=14) o ambos (n=17). El rescate (52%), y la toxicidad farmacológica (20%) fueron las principales indicaciones de tratamiento con maraviroc. La incidencia de hipertransaminasemia de grado 3-4 (AST o ALT >5 veces el LSN), por 100 paciente-años de exposición a maraviroc, fue 5,84 (IC 95%, 4,04-8,16) y 1,23 (IC 95%, 0,56-2,33) en coinfectados y monoinfectados por VIH, respectivamente (razón de tasas, 4,77; IC95%, 2,35-10,5). No se observaron diferencias en la proporción acumulada de pacientes con elevación de AST o ALT mayor de 3,5 veces respecto al valor basal, ni en la progresión de la fibrosis hepática entre ambos grupos. Tras una mediana de tratamiento de 20 meses (AIC, 12-41), dos pacientes (0,3%) discontinuaron el maraviroc por hepatitis de grado 4, y dos pacientes fallecieron por enfermedad hepática. Conclusiones: En una cohorte española de pacientes infectados por VIH que incluye más de 300 pacientes coinfectados por VHC y/o VHB, maraviroc mostró una baja incidencia de hepatitis. La coinfección no afectó al grado de elevación de las transaminasas ni a la progresión de la fibrosis hepática (AU)