Mark Nelson1, Gail V Matthews2,3, Marianne Martinello2,3,4, Chloe Orkin5, Graham Cooke6, Sanjay Bhagani7, Edward Gane8, Ranjababu Kulasegaram9, David Shaw10, Elise Tu2, Kathy Petoumenos2, Philippa Marks2, Jason Grebely2, Gregory J Dore2,3. 1. Chelsea and Westminster Hospital, London, UK. 2. Kirby Institute, University of New South Wales Sydney, Sydney, Australia. 3. St. Vincent's Hospital, Sydney, Australia. 4. Department of Infectious Diseases, Blacktown Mt. Druitt Hospital, Sydney, Australia. 5. Queen Mary University of London, London, UK. 6. Department of Infectious Diseases, Imperial College NHS Trust, St. Mary's Hospital, London, UK. 7. Department of Infectious Diseases/HIV Medicine, Royal Free Hospital, London, UK. 8. New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand. 9. Guy's and St. Thomas' Hospital, London, UK. 10. Department of Infectious Diseases, Royal Adelaide Hospital, Adelaide, Australia.
Abstract
BACKGROUND AND AIMS: Among treatment-naive individuals with chronic hepatitis C viral (HCV) infection and without cirrhosis, glecaprevir/pibrentasvir for 8 weeks is recommended. The aim of this analysis was to evaluate the efficacy of glecaprevir/pibrentasvir for 6 weeks in people with acute and recent HCV infection. APPROACH AND RESULTS: In this open-label, single-arm, multicenter, international pilot study, adults with recent HCV (duration of infection < 12 months) received glecaprevir/pibrentasvir 300/120 mg daily for 6 weeks. Primary infection was defined by first positive anti-HCV antibody and/or HCV RNA within 6 months of enrollment and either acute clinical hepatitis within the past 12 months (symptomatic seroconversion illness or alanine aminotransferase > 10 × upper limit of normal) or anti-HCV antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months of enrollment and evidence of prior spontaneous or treatment-induced clearance. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Thirty men (median age 43 years, 90% men who have sex with men) received treatment, of whom 77% (n = 23) were human immunodeficiency virus-positive, 47% (n = 14) had ever injected drugs, and 13% (n = 4) had HCV reinfection. The majority had HCV genotype 1 (83%, n = 25), followed by genotype 4 (10%, n = 3) and genotype 3 (7%, n = 2). At baseline, median estimated duration of infection was 29 weeks (range 13, 52) and median HCV RNA was 6.2 log10 IU/mL (range 0.9, 7.7). SVR12 in the intention-to-treat and per-protocol populations was achieved in 90% (27/30) and 96% (27/28), respectively. There was one case of relapse, and there were two cases of nonvirological failure (death, n = 1; loss to follow-up, n = 1). No treatment-related serious adverse events were seen. CONCLUSIONS: Glecaprevir/pibrentasvir for 6 weeks was highly effective among people with acute and recent HCV infection, supporting further evaluation of shortened-duration pan-genotypic therapy in this setting.
BACKGROUND AND AIMS: Among treatment-naive individuals with chronic hepatitis C viral (HCV) infection and without cirrhosis, glecaprevir/pibrentasvir for 8 weeks is recommended. The aim of this analysis was to evaluate the efficacy of glecaprevir/pibrentasvir for 6 weeks in people with acute and recent HCV infection. APPROACH AND RESULTS: In this open-label, single-arm, multicenter, international pilot study, adults with recent HCV (duration of infection < 12 months) received glecaprevir/pibrentasvir 300/120 mg daily for 6 weeks. Primary infection was defined by first positive anti-HCV antibody and/or HCV RNA within 6 months of enrollment and either acute clinical hepatitis within the past 12 months (symptomatic seroconversion illness or alanine aminotransferase > 10 × upper limit of normal) or anti-HCV antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months of enrollment and evidence of prior spontaneous or treatment-induced clearance. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Thirty men (median age 43 years, 90% men who have sex with men) received treatment, of whom 77% (n = 23) were human immunodeficiency virus-positive, 47% (n = 14) had ever injected drugs, and 13% (n = 4) had HCV reinfection. The majority had HCV genotype 1 (83%, n = 25), followed by genotype 4 (10%, n = 3) and genotype 3 (7%, n = 2). At baseline, median estimated duration of infection was 29 weeks (range 13, 52) and median HCV RNA was 6.2 log10 IU/mL (range 0.9, 7.7). SVR12 in the intention-to-treat and per-protocol populations was achieved in 90% (27/30) and 96% (27/28), respectively. There was one case of relapse, and there were two cases of nonvirological failure (death, n = 1; loss to follow-up, n = 1). No treatment-related serious adverse events were seen. CONCLUSIONS:Glecaprevir/pibrentasvir for 6 weeks was highly effective among people with acute and recent HCV infection, supporting further evaluation of shortened-duration pan-genotypic therapy in this setting.
Authors: Evan Gorstein; Marianne Martinello; Alexander Churkin; Swikriti Dasgupta; Kevin Walsh; Tanya L Applegate; David Yardeni; Ohad Etzion; Susan L Uprichard; Danny Barash; Scott J Cotler; Gail V Matthews; Harel Dahari Journal: Antiviral Res Date: 2020-06-25 Impact factor: 5.970
Authors: Lone W Madsen; Peer B Christensen; Janne F Hansen; Birgit T Røge; Dorte K Holm; Sandra Dröse; Anne Øvrehus Journal: Viruses Date: 2022-03-16 Impact factor: 5.048