Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine
Name
11987.full.pdf
Description
Published version
Size
1.41 MB
Format
Adobe PDF
Checksum (MD5)
8734ec0c6c8cf47750993a2862e329da
Author(s)
Verma, Malvika
Chu, Jacqueline N
Salama, John Ashraf Fou
Faiz, Mohammed T.
Eweje, Feyisope
Gwynne, Declan A
Lopes, Aaron C
Hess, Kaitlyn
Soares, Vance
Steiger, Christoph Winfried Johannes
Date Issued
May 2020
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences
Citation
Verma, Malvika et al. "Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine." Proceedings of the National Academy of Sciences of the United States of America 117, 22 (May 2020): 11987-11994 © 2020 National Academy of Sciences
Version
Final published version
Abstract
Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis worldwide and kills more Americans than 59 other infections, including HIV and tuberculosis, combined. While direct-acting antiviral (DAA) treatments are effective, limited uptake of therapy, particularly in high-risk groups, remains a substantial barrier to eliminating HCV. We developed a long-acting DAA system (LA-DAAS) capable of prolonged dosing and explored its cost-effectiveness. We designed a retrievable coil-shaped LA-DAAS compatible with nasogastric tube administration and the capacity to encapsulate and release gram levels of drugs while resident in the stomach. We formulated DAAs in drug-polymer pills and studied the release kinetics for 1 mo in vitro and in vivo in a swine model. The LA-DAAS was equipped with ethanol and temperature sensors linked via Bluetooth to a phone application to provide patient engagement. We then performed a cost-effectiveness analysis comparing LA-DAAS to DAA alone in various patient groups, including people who inject drugs. Tunable release kinetics of DAAs was enabled for 1 mo with drug-polymer pills in vitro, and the LA-DAAS safely and successfully provided at least month-long release of sofosbuvir in vivo. Temperature and alcohol sensors could interface with external sources for at least 1 mo. The LA-DAAS was cost-effective compared to DAA therapy alone in all groups considered (base case incremental cost-effectiveness ratio $39,800). We believe that the LA-DAA system can provide a cost-effective and patient-centric method for HCV treatment, including in high-risk populations who are currently undertreated.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Tata Center for Technology and Design
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
Sloan School of Management
Massachusetts Institute of Technology. Department of Mechanical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.2004746117
