title: Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study.
abstract: To shorten the course of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, we examined the antiviral efficacy and safety of 3 weeks of response-guided therapy with an NS3 protease inhibitor and dual NS5A inhibitor-NS5B nucleotide analogue.
  
  
  
  In this open-label, phase 2a, single centre study, Chinese patients with chronic HCV genotype 1b infection without cirrhosis were randomly allocated by a computer program to one of three treatment groups (sofosbuvir, ledipasvir, and asunaprevir; sofosbuvir, daclatasvir, and simeprevir; or sofosbuvir, daclatasvir, and asunaprevir) until six patients in each group (1:1:1) achieved an ultrarapid virological response (plasma HCV RNA <500 IU/mL by day 2, measured by COBAS TaqMan HCV test, version 2.0). Patients with an ultrarapid virological response received 3 weeks of therapy. Patients who did not achieve an ultrarapid response were switched to sofosbuvir and ledipasvir for either 8 weeks or 12 weeks. The primary endpoint was the proportion of patients with a sustained virological response at 12 weeks (SVR12) after treatment completion, analysed in the intention-to-treat population. All patients who achieved an ultrarapid virological response were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02470858.
  
  
  
  Between April 5, 2015, and April 15, 2015, 26 eligible patients were recruited. 12 patients were assigned to sofosbuvir, ledipasvir, and asunaprevir; six to sofosbuvir, daclatasvir, and simeprevir; and eight to sofosbuvir, daclatasvir, and asunaprevir. Six patients in each group achieved an ultrarapid virological response (18 [69%]). All patients with an ultrarapid virological response who were given 3 weeks of triple therapy achieved SVR12. The most common adverse events were fatigue (one [17%] of six patients receiving sofosbuvir, ledipasvir, and asunaprevir; one [17%] of six patients receiving sofosbuvir, daclatasvir, and simeprevir; and two [33%] of six patients receiving sofosbuvir, daclatasvir, and asunaprevir) and headache (one [17%] patient in each group). No patients experienced any serious adverse events.
  
  
  
  In this proof-of-concept study, all patients with chronic HCV without cirrhosis who achieved an ultrarapid virological response on triple direct-acting antiviral regimens by day 2 and received 3 weeks of treatment were cured, with excellent tolerability. By shortening the duration of therapy from the currently recommended 12 weeks to 3 weeks, we could drastically reduce the cost of therapy and the rate of adverse events. Further large-scale studies should be done to confirm our findings.
  
  
  
  Center for AIDS Research, National Institutes of Health, US Department of Energy, National Center for Research Resources and the Office of Research Infrastructure Programs, Cheng Si-Yuan (China-International) Hepatitis Research Foundation, and Humanity and Health Medical Group.
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: George
authors.initials: G
authors.lastname: Lau
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Yves
authors.initials: Y
authors.lastname: Benhamou
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Guofeng
authors.initials: G
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Qing
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Dong
authors.initials: D
authors.lastname: Ji
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Jialiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Vanessa
authors.initials: V
authors.lastname: Wu
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: April
authors.initials: A
authors.lastname: Wong
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Chris L P
authors.initials: CL
authors.lastname: Wong
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Stella T Y
authors.initials: ST
authors.lastname: Tsang
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Yudong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Leda
authors.initials: L
authors.lastname: Bassit
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Sijia
authors.initials: S
authors.lastname: Tao
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Hui-Mien
authors.initials: HM
authors.lastname: Hsiao
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Ruian
authors.initials: R
authors.lastname: Ke
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.affiliation: Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, Hong Kong SAR, China (Prof G Lau MD, C Wang MD, J Chen PhD, V Wu BSc, A Wong BSc, Y Wang PhD); Second Liver Cirrhosis Diagnosis and Treatment Center (Prof G Lau, Prof G Chen MD, Prof Q Shao MD, D Ji MD, F Li MD, B Li MD, J Liu MD) and Institute of Infectious Disease (Prof J Li MD), 302 Hospital, Beijing, China; Service d'Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France (Y Benhamou MD); State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China (Prof J Hou MD, Prof J Sun MD, C Wang); Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China (C L P Wong PhD, S T Y Tsang PhD); Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA (L Bassit PhD, S Tao PhD, Y Jiang PhD, H-M Hsiao MS, Prof R F Schinazi PhD); Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM, USA (R Ke PhD, A S Perelson PhD); and Department of Mathematics, North Carolina State University, Raleigh, NC, USA (R Ke).
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D002219:Carbamates; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000627:therapeutic use; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D007546:Isoquinolines / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000075082:Proof of Concept Study; D011759:Pyrrolidines; D000069616:Simeprevir / Q000008:administration & dosage / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D005449:Fluorenes; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; C586541:ledipasvir; D000069616:Simeprevir; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir; D000069474:Sofosbuvir