BACKGROUND: The latest European Association for the Study of the Liver (EASL) guidelines now recommend that patients with acute hepatitis C virus (HCV) infection should be treated with a combination of sofosbuvir and an NS5A inhibitor for 8 weeks. However, the ideal duration of treatment with interferon-free regimens, particularly in HIV-coinfected individuals, remains unknown. We assessed the efficacy and safety of 6 weeks of ledipasvir-sofosbuvir for acute genotype 1 or 4 HCV in HIV-1-coinfected patients. METHODS: This open-label, single-arm trial, done in Germany and the UK, included patients with acute HCV genotype 1 or 4 and HIV-1. At screening, patients were either receiving HIV antiretrovirals and had HIV RNA less than 200 copies per mL, or not receiving antiretrovirals and had a CD4 T-cell count of greater than 500 cells per μL. All patients received ledipasvir-sofosbuvir once daily for 6 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12). This study is registered with ClinicalTrials.gov, number NCT02457611. FINDINGS: Between June 11, 2015, and Jan 8, 2016, we enrolled and treated 26 patients. All (100%) were men, 24 (92%) were white, and 25 (96%) were receiving antiretroviral treatment. 19 (73%) had genotype 1a and seven (27%) had genotype 4 HCV. Overall, 20 (77%; 95% CI 56-91) of 26 patients achieved SVR12: 15 (79%) of 19 with genotype 1a, and five (71%) of seven with genotype 4. Of six patients not achieving SVR12, three relapsed, two achieved sustained virological response 4 weeks after the end of treatment but were lost to follow-up, and one was reinfected. The most common adverse events were fatigue (seven participants [27%]), nasopharyngitis (seven [27%]), and headache (six [23%]). No patient discontinued or interrupted therapy due to adverse events. No HIV rebound occurred during the study. INTERPRETATION: The rate of cure with a fixed-dose combination of ledipasvir-sofosbuvir for patients with acute genotype 1 or 4 HCV infection and HIV-1 coinfection is similar to historic rates with interferon-based treatment, but with shorter treatment duration and more favourable safety outcomes. FUNDING: Gilead Sciences.
BACKGROUND: The latest European Association for the Study of the Liver (EASL) guidelines now recommend that patients with acute hepatitis C virus (HCV) infection should be treated with a combination of sofosbuvir and an NS5A inhibitor for 8 weeks. However, the ideal duration of treatment with interferon-free regimens, particularly in HIV-coinfected individuals, remains unknown. We assessed the efficacy and safety of 6 weeks of ledipasvir-sofosbuvir for acute genotype 1 or 4 HCV in HIV-1-coinfectedpatients. METHODS: This open-label, single-arm trial, done in Germany and the UK, included patients with acute HCV genotype 1 or 4 and HIV-1. At screening, patients were either receiving HIV antiretrovirals and had HIV RNA less than 200 copies per mL, or not receiving antiretrovirals and had a CD4 T-cell count of greater than 500 cells per μL. All patients received ledipasvir-sofosbuvir once daily for 6 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12). This study is registered with ClinicalTrials.gov, number NCT02457611. FINDINGS: Between June 11, 2015, and Jan 8, 2016, we enrolled and treated 26 patients. All (100%) were men, 24 (92%) were white, and 25 (96%) were receiving antiretroviral treatment. 19 (73%) had genotype 1a and seven (27%) had genotype 4 HCV. Overall, 20 (77%; 95% CI 56-91) of 26 patients achieved SVR12: 15 (79%) of 19 with genotype 1a, and five (71%) of seven with genotype 4. Of six patients not achieving SVR12, three relapsed, two achieved sustained virological response 4 weeks after the end of treatment but were lost to follow-up, and one was reinfected. The most common adverse events were fatigue (seven participants [27%]), nasopharyngitis (seven [27%]), and headache (six [23%]). No patient discontinued or interrupted therapy due to adverse events. No HIV rebound occurred during the study. INTERPRETATION: The rate of cure with a fixed-dose combination of ledipasvir-sofosbuvir for patients with acute genotype 1 or 4 HCV infection and HIV-1 coinfection is similar to historic rates with interferon-based treatment, but with shorter treatment duration and more favourable safety outcomes. FUNDING: Gilead Sciences.
Authors: David Chromy; Mattias Mandorfer; Theresa Bucsics; Philipp Schwabl; Bernhard Scheiner; Caroline Schmidbauer; Maximilian Christopher Aichelburg; Peter Ferenci; Michael Trauner; Markus Peck-Radosavljevic; Thomas Reiberger Journal: United European Gastroenterol J Date: 2019-03-06 Impact factor: 4.623
Authors: Susanna Naggie; Daniel S Fierer; Michael D Hughes; Arthur Y Kim; Annie Luetkemeyer; Vincent Vu; Jhoanna Roa; Steve Rwema; Diana M Brainard; John G McHutchison; Marion G Peters; Jennifer J Kiser; Kristen M Marks; Raymond T Chung Journal: Clin Infect Dis Date: 2019-07-18 Impact factor: 20.999
Authors: Juan Berenguer; José Luis Calleja; María Luisa Montes; Ángela Gil; Ana Moreno; Rafael Bañares; Teresa Aldámiz-Echevarría; Agustín Albillos; María Jesús Téllez; Antonio Olveira; Lourdes Domínguez; Inmaculada Fernández; Javier García-Samaniego; Benjamín A Polo; Beatriz Álvarez; Pablo Ryan; José Barrio; María J Devesa; Laura Benítez; Ignacio Santos; Luisa García Buey; José Sanz; Elvira Poves; Juan E Losa; Conrado Fernández-Rodríguez; Inmaculada Jarrín; María J Calvo; Juan González-García Journal: Open Forum Infect Dis Date: 2019-05-07 Impact factor: 3.835
Authors: Paari M Palaniswami; Ahmed El Sayed; Benjamin Asriel; Jesse R Carollo; Daniel S Fierer Journal: Open Forum Infect Dis Date: 2018-09-21 Impact factor: 3.835