Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Antiviral Res. 2017 Aug;144:281-285. doi: 10.1016/j.antiviral.2017.06.019. Epub 2017 Jun 30.

Modeling HCV cure after an ultra-short duration of therapy with direct acting agents.

Author information

1
The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL, United States; Theoretical Biology & Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, United States.
2
Liver Unit, Digestive Disease Institute, Sha'are Zedek Medical Center, Jerusalem, Israel.
3
Division of Infectious Diseases, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, United States; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
4
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
5
The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL, United States; Department of Microbiology and Immunology, University of Illinois Chicago, Chicago, IL, United States.
6
The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL, United States.
7
The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL, United States. Electronic address: hdahari@luc.edu.

Abstract

BACKGROUND:

Cases of sustained-virological response (SVR or cure) after an ultra-short duration (≤27 days) of direct-acting antiviral (DAA)-based therapy, despite HCV being detected at end of treatment (EOT), have been reported. Established HCV mathematical models that predict the treatment duration required to achieve cure do not take into account the possibility that the infectivity of virus produced during treatment might be reduced. The aim of this study was to develop a new mathematical model that considers the fundamental and critical concept that HCV RNA in serum represents both infectious virus (Vi) and non-infectious virus (Vni) in order to explain the observation of cure with ultrashort DAA therapy.

METHODS:

Established HCV models were compared to the new mathematical model to retrospectively explain cure in 2 patients who achieved cure after 24 or 27 days of paritaprevir, ombitasvir, dasabuvir, ritonavir and ribavirin or sofosbuvir plus ribavirin, respectively.

RESULTS:

Fitting established models with measured longitudinal HCV viral loads indicated that in both cases, cure would not have been expected without an additional 3-6 weeks of therapy after the actual EOT. In contrast, the new model fits the observed outcome by considering that in addition to blocking Vi and Vni production (ε∼0.998), these DAA + ribavirin treatments further enhanced the ratio of Vni to Vi, thus increasing the log (Vni/Vi) from 1 at pretreatment to 6 by EOT, which led to <1 infectious-virus particle in the extracellular body fluid (i.e., cure) prior to EOT.

CONCLUSIONS:

This new model can explain cure after short duration of DAA + ribavirin therapy by suggesting that a minimum 6-fold increase of log (Vni/Vi) results from drug-induced enhancement of the Vni/Vi.

PMID:
28673800
PMCID:
PMC5962520
DOI:
10.1016/j.antiviral.2017.06.019
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center