1. Academic Validation
  2. A proof-of-concept study in HCV-infected Huh7.5 cells for shortening the duration of DAA-based triple treatment regimens

A proof-of-concept study in HCV-infected Huh7.5 cells for shortening the duration of DAA-based triple treatment regimens

  • Biomed Pharmacother. 2019 Aug;116:108976. doi: 10.1016/j.biopha.2019.108976.
Hu Li 1 Jia-Li Tan 1 Jian-Rui Li 1 Nan-Nan Liu 1 Jin-Hua Chen 1 Xiao-Qin Lv 1 Li-Li Zou 1 Biao Dong 1 Zong-Gen Peng 2 Jian-Dong Jiang 3
Affiliations

Affiliations

  • 1 Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
  • 2 Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Key Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: pumcpzg@126.com.
  • 3 Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Key Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: jiang.jdong@163.com.
Abstract

With the development of more effective direct-acting antivirals (DAAs), dual- or triple-therapy regimens represent the major strategy used to cure chronic hepatitis C virus (HCV) Infection. Thus, shorter treatment duration regimens with low burden, few adverse effects and good patient adherence are urgently needed. This study theoretically demonstrates a proof-of-concept approach for shortening therapy duration by examining HCV-infected Huh7.5 cells after treatment with a high or low fixed dose of three DAAs (simeprevir + daclatasvir + sofosbuvir) for 6-15 days. The results demonstrated that HCV-infected Huh7.5 cells achieved an ultrarapid virologic response with undetectable HCV RNA and protein and were cured after treatment with the triple-therapy regimen for 15 days. When the treatment duration was shortened, virologic relapse might occur after treatment with a low fixed dose of the three DAAs for 9 days and did occur after treatment with a low fixed dose for 6 days, although HCV was below detectable levels at the end of treatment. However, virologic relapse could be avoided with treatment of a high fixed dose of the three DAAs for 9 or 6 days. Although a virologic breakthrough occurred after an intermittent treatment regimen at the low fixed dose, the high fixed dose cured HCV-positive Huh7.5 cells with intermittent treatment. In conclusion, HCV is persistently present below detectable levels in HCV-infected Huh7.5 cells for a long time after treatment, and a shortened therapy duration is associated with an increased risk of virologic relapse, but virologic relapse or breakthrough might be avoided by treatment with a combination of more highly effective DAAs.

Keywords

DAA treatment regimens; HCV-positive hepatocytes; Hepatitis C virus; Shorter therapy duration; Virologic relapse.

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