top of page

Efficacy and Safety of Modeling-Based Response Guided Therapy with Direct Acting Anti-Viral Agents for Treatment Optimization in Chronic Hepatitis C Infection- A Pilot Study

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


October 2020



The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. However, the high cost of DAAs therapy has become a major barrier to HCV elimination. We aimed to prospectively evaluate the efficacy and safety of reducing the duration of DAAs therapy using response-guided therapy approach based on mathematical modeling of viral kinetics.

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. Sofosbuvir/velpatasvir, elbasvir/grazoprevir, sofosbuvir/ledipasvir and glecaprevir/pibrentasvir, were administered in 38%, 27%, 21% and 14% of patients, respectively. 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 modeling can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy. Implementation of this model on a wider scale may lead to significant cost-saving and to improved access to anti-HCV care.

Funding: The study was supported in part by NIH grants R01AI078881 and R01GM121600.

Research in context

Evidence before the study:
Treatment with DAAs lead to cure from HCV infection in over 95% of infected patients. However, the high cost of these new drugs is a major obstacle to achieving viral elimination. Results of previous retrospective studies on mathematical modeling of viral kinetics during early stages of DAAs therapy, have suggested that HCV cure can be reached with a shorter duration of treatment in a substantial proportion of patients.

Added value of this study:
To our knowledge, this is the first prospective clinical trial assessing the utility of a response guided therapy approach based on mathematical modeling to individualize treatment duration with DAAs in CHC. Model-based decisions led to treatment shortening in 38% of patients and to an overall time saving of 14% in treatment duration. Implementation of the model was safe and did not compromise treatment efficacy.

Implications of all the available evidence:

Implementation of an RGT approach for treatment of HCV on a larger scale could lead to a significant reduction in treatment cost. This may improve access to HCV care especially in resource limited settings and facilitate the goal of HCV elimination.

bottom of page