Effectiveness and safety of glecaprevir/pibrentasvir for 8 weeks in the treatment of patients with acute hepatitis C: A single-arm retrospective study.

BACKGROUND AND AIMS: No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection. APPROACH AND RESULTS: This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection. Analyses were conducted on a full analysis set (FAS; all enrolled) and modified FAS (FAS excluding nonvirologic failures). The primary end point (modified FAS) was sustained virologic response at posttreatment week 12 (SVR12) with superiority to 92.6% threshold determined by historic chronic HCV G/P SVR12 rates. Secondary end points (FAS) included SVR12, on-treatment virologic failure, posttreatment relapse, and reinfection. Adverse events and safety laboratory values were assessed.Overall, 202 adults were enrolled; in the modified FAS, 150/151 (99.3%; 95% CI: 96.3-99.9) achieved SVR12, demonstrating superiority to efficacy threshold. In the FAS, the SVR12 rate was 74.3% and the on-treatment virologic failure rate was 0%. Relapse and reinfection rates after the final treatment visit (FAS) were 0.5% and 3%, respectively; 39 patients had missing SVR12 data. No on-treatment alanine aminotransferase elevations > 3 × upper limit of normal with total bilirubin > 2 × upper limit of normal were reported. All 53 patients with alanine aminotransferase Grade ≥ 2 at baseline improved to Grade 0/1 on treatment. No adverse eventss of hepatic decompensation/failure or leading to G/P discontinuation occurred. Two patients had serious adverse events unrelated to G/P. CONCLUSIONS: Eight-week G/P therapy was effective and well-tolerated in patients with acute HCV infection. Data support further investigation of G/P in acute HCV to shorten care cascades, reduce transmission, and support HCV elimination.

Efficacy of Elbasvir/Grazoprevir in Early Chronic G1/G4 Hepatitis C infection in HIV/HCV co-infected patients with mild fibrosis / Eficacia de elbasvir/grazoprevir en la infección por hepatitis C crónica reciente G1/G4 en pacientes coinfectados por el VIH/VHC con fibrosis leve

Background: Acute hepatitis C virus (AHC) infection is increasingly common among HIV+ men who have sex with men (MSM). Until 2017, the guidelines recommended therapy with pegylated-interferon plus ribavirin with a mild sustained virological response (SVR). This prompted many patients to reject that treatment, at that time, waiting to be treated with better and safer options with new Direct-Acting-Antivirals (DAA). Objectives: Assess the efficacy and safety of Elbasvir/Grazoprevir to treat recent chronic hepatitis C infection, genotype 1 or 4, in HIV+ MSM patients. Methods: Prospective, open-labeled, two center, pilot study. SVR is analyzed for treatment with Elbasvir/Grazoprevir (8 weeks in GT1b or 12 in GT1a or GT4) in patients with a recent chronic HCV infection, defined as HCV infection lasting less than 4 years and mild liver fibrosis (liver stiffness <8kPa). Results: Forty-eight patients were included (May 2017–March 2018): 2 GT1b, 24 GT1a and 22 GT4. HCV-RNA>800000UI in 63% and medium liver stiffness 4.9kPa. The SVR was 98%, one patient failed due to poor adherence. 67% of patients had adverse effects, but only 16% treatment related. The most frequent side effects were gastrointestinal (19%), related with the central nervous system (18%), respiratory (16%) and systemic symptoms (15%).During one year of follow-up post-therapy, 4 AHC and 18 patients with sexually transmitted diseases (STD) were diagnosed. Conclusions: Treatment with Elbasvir/Grazoprevir in this scenario is highly effective and safe. Patients with risky sexual practices must remain linked to the medical care system to detect new STD and HCV reinfection.(AU)

Antecedentes: La infección aguda por el virus de la hepatitis C (HCA) es cada vez más frecuente entre los hombres VIH+ que mantienen relaciones sexuales con hombres (HSH). Hasta 2017, las directrices recomendaban el tratamiento con interferón pegilado más ribavirina con una respuesta virológica sostenida (RVS) leve. Esto llevó a muchos pacientes a rechazar dicho tratamiento en ese momento, a la espera de recibir tratamiento con opciones mejores y más seguras con los nuevos antivirales de acción directa (AAD). Objetivos: Evaluar la eficacia y la seguridad de elbasvir/grazoprevir para tratar la infección por hepatitis C crónica reciente, genotipo 1 o 4, en pacientes HSH VIH+. Métodos: Estudio preliminar, prospectivo, abierto y realizado en 2 centros. Se evalúa la RVS para el tratamiento con elbasvir/grazoprevir (8 semanas en GT1b o 12 en GT1a o GT4) en pacientes con una infección por VHC crónica reciente, definida como una infección por VHC que dura menos de 4 años y fibrosis hepática leve (rigidez hepática <8kPa). Resultados: Se incluyeron 48 pacientes (mayo de 2017-marzo de 2018): 2 en GT1b, 24 en GT1a y 22 en GT4. ARN-VHC>800.000UI en el 63% y rigidez hepática media de 4,9Kpa. La RVS fue del 98%; un paciente fracasó debido a un cumplimiento terapéutico deficiente. El 67% de los pacientes presentó efectos adversos, pero solo el 16% estuvo relacionado con el tratamiento. Los efectos secundarios más frecuentes fueron síntomas gastrointestinales (19%), relacionados con el sistema nervioso central (18%), respiratorios (16%) y sistémicos (15%). Durante un año de seguimiento postratamiento se diagnosticaron 4 HCA y 18 pacientes con enfermedades de transmisión sexual (ETS). Conclusiones: El tratamiento con elbasvir/grazoprevir en este contexto es muy eficaz y seguro. Los pacientes con prácticas sexuales de riesgo deben permanecer vinculados al sistema de asistencia médica para detectar nuevas ETS y reinfecciones por VHC.(AU)

Efficacy of Elbasvir/Grazoprevir in Early Chronic G1/G4 Hepatitis C infection in HIV/HCV co-infected patients with mild fibrosis.

BACKGROUND: Acute hepatitis C virus (AHC) infection is increasingly common among HIV+ men who have sex with men (MSM). Until 2017, the guidelines recommended therapy with pegylated-interferon plus ribavirin with a mild sustained virological response (SVR). This prompted many patients to reject that treatment, at that time, waiting to be treated with better and safer options with new Direct-Acting-Antivirals (DAA). OBJECTIVES: Assess the efficacy and safety of Elbasvir/Grazoprevir to treat recent chronic hepatitis C infection, genotype 1 or 4, in HIV+ MSM patients. METHODS: Prospective, open-labeled, two center, pilot study. SVR is analyzed for treatment with Elbasvir/Grazoprevir (8 weeks in GT1b or 12 in GT1a or GT4) in patients with a recent chronic HCV infection, defined as HCV infection lasting less than 4 years and mild liver fibrosis (liver stiffness <8kPa). RESULTS: Forty-eight patients were included (May 2017-March 2018): 2 GT1b, 24 GT1a and 22 GT4. HCV-RNA>800000UI in 63% and medium liver stiffness 4.9kPa. The SVR was 98%, one patient failed due to poor adherence. 67% of patients had adverse effects, but only 16% treatment related. The most frequent side effects were gastrointestinal (19%), related with the central nervous system (18%), respiratory (16%) and systemic symptoms (15%). During one year of follow-up post-therapy, 4 AHC and 18 patients with sexually transmitted diseases (STD) were diagnosed. CONCLUSIONS: Treatment with Elbasvir/Grazoprevir in this scenario is highly effective and safe. Patients with risky sexual practices must remain linked to the medical care system to detect new STD and HCV reinfection.

Tratamiento de la hepatitis por virus C en pacientes coinfectados por el virus de la inmunodeficiencia humana / Treatment of hepatitis C virus in HIV-positive patients

La coinfección por VIH-VHC ocurre actualmente en más del 30% de los pacientes infectados por VIH en nuestro país. En la actualidad, interferón pegilado más ribavirina constituye el tratamiento de elección para la hepatitis crónica por VHC en pacientes VIH. Con ello se obtienen unas tasas de curación global algo inferiores a las obtenidas en los monoinfectados por el VHC y cercanas al 50% de los pacientes. El desarrollo de efectos adversos relacionados con la medicación es muy frecuente y en un 10-20% de los casos conduce al abandono del tratamiento. Son de destacar 3 nuevos aspectos de la hepatitis C en pacientes VIH: 1) aparición en los últimos años de brotes epidémicos de hepatitis aguda por VHC en pacientes VIH varones a partir de relaciones homosexuales; 2) marcadores farmacogenéticos en forma de polimorfismos genéticos cercanos al gen de IL28B relacionados con la respuesta al tratamiento del VHC así como con la erradicación espontánea del VHC tras la infección aguda, y 3) nuevas moléculas antivirales cuyos resultados preliminares en ensayos clínicos son muy esperanzadores por cuanto permiten diseñar tratamientos combinados triples que alcanzan altas tasas de respuesta (AU)

Hepatitis C virus (HCV)-HIV coinfection currently occurs in more than 30% of HIV-positive patients in Spain. Nowadays, the treatment of choice for chronic hepatitis due to HCV infection in HIV-positive patients is pegylated interferon plus ribavirin. This combination achieves an overall cure rate of 50%, which is somewhat lower than those obtained in patients with HCV monoinfection. Adverse effects are frequent, leading to treatment withdrawal in 10-20% of patients.Importantly, there are three new features of hepatitis C in patients with HIV: (1) the recent development of epidemic outbreaks of acute hepatitis due to HCV infection in HIV-positive men caused by homosexual activity, (2) pharmacogenetic markers in the form of genetic polymorphisms near the IL28B gene related to response to HCV treatment as well as spontaneous eradication of HCV after acute infection, and (3) new antiviral molecules have allowed triple combination treatments to be designed and the preliminary results of clinical trials reporting high response rates are highly promising (AU)

[Treatment of hepatitis C virus in HIV-positive patients]. / Tratamiento de la hepatitis por virus C en pacientes coinfectados por el virus de la inmunodeficiencia humana.

Hepatitis C virus (HCV)-HIV coinfection currently occurs in more than 30% of HIV-positive patients in Spain. Nowadays, the treatment of choice for chronic hepatitis due to HCV infection in HIV-positive patients is pegylated interferon plus ribavirin. This combination achieves an overall cure rate of 50%, which is somewhat lower than those obtained in patients with HCV monoinfection. Adverse effects are frequent, leading to treatment withdrawal in 10-20% of patients. Importantly, there are three new features of hepatitis C in patients with HIV: (1) the recent development of epidemic outbreaks of acute hepatitis due to HCV infection in HIV-positive men caused by homosexual activity, (2) pharmacogenetic markers in the form of genetic polymorphisms near the IL28B gene related to response to HCV treatment as well as spontaneous eradication of HCV after acute infection, and (3) new antiviral molecules have allowed triple combination treatments to be designed and the preliminary results of clinical trials reporting high response rates are highly promising.