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

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.

Mathematical modeling suggests that entry-inhibitor bulevirtide may interfere with hepatitis D virus clearance from circulation

“…Reminiscent of the notion of predicting the duration of anti-HCV treatment needed to reach <1 virus copy in a patient's total extracellular-body fluid (BF) [5], modeling predicts <1 HDV copy per BF after 75, 50 and 90 weeks of 10 mg/day BLV in patients 1, 2 and 3, respectively(Fig. S3).…”

Four Weeks Treatment with Glecaprevir/Pibrentasvir + Ribavirin—A Randomized Controlled Clinical Trial

“…Another approach to reduce treatment duration is response-guided therapy. Here an on-treatment viral kinetic is used to individualize treatment duration without compromising the SVR12 rate [ 26 , 27 ]. In our study, we could not find any difference between measurable HCV RNA at treatment week two for patients who were cured and for those with virological relapse.…”

Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance

“…With the advent of DAA therapy, many patients are treated successfully for HCV before liver transplantation [22]. Nevertheless, the finding of viral steady state during anhepatic phase in the majority of patients and the rapid uptake of HCV by the liver during reperfusion reinforces the benefit of achieving not only viral negativity but also achieving less than one virus particle in the entire extracellular body fluid (i.e., cure boundary recently used in [23]) with DAA therapy prior to transplantation to prevent infection of the graft.…”

“…Five transplant recipients (termed Cases) with median age 60 years (range, 49-68) and median BMI 30 kg/m 2 (range, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] underwent liver transplantation (Table 1). Four of the five liver donors were male with median age 69 years (range, 29-73) (Table 1).…”