Response guided therapy for reducing duration of direct acting antivirals in chronic hepatitis C infected patients: a Pilot study

Ohad Etzion*, Harel Dahari*, David Yardeni, Assaf Issachar, Anat Nevo-Shor, Michal Cohen-Naftaly, Yaffa Ashur, Susan L. Uprichard, Orly Sneh Arbib, Daniela Munteanu, Marius Braun, Scott J. Cotler, Naim Abufreha, Ayelet Keren-Naus, Yonat Shemer-Avni, Orna Mor, Jayanah Murad, Victor Novack, Amir Shlomai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. We aimed to prospectively (real-time) evaluate the feasibility of using a response-guided therapy approach, based on mathematical modeling of early viral kinetics, to reduce the duration of DAAs therapy. Patients were treated with DAAs according to the physicians’ preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment. Twenty-nine patients (mean age 54 ± 16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions. Real-time mathematical modeling of early HCV kinetics can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy. Clinical trial registration: ClinicalTrials.gov Identifier: NCT03603327.

Original languageEnglish
Article number17820
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2020

Funding

FundersFunder number
National Institutes of HealthR01-AI078881
National Institute of General Medical SciencesR01GM121600
Clalit Health Services

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