Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine

Malvika Verma, Jacqueline N. Chu, John A.F. Salama, Mohammed T. Faiz, Feyisope Eweje, Declan Gwynne, Aaron Lopes, Kaitlyn Hess, Vance Soares, Christoph Steiger, Rebecca McManus, Ryan Koeppen, Tiffany Hua, Alison Hayward, Joy Collins, Siddartha M. Tamang, Keiko Ishida, Jonathan B. Miller, Stephanie Katz, Alexander H. SlocumMark S. Sulkowski, David L. Thomas, Robert Langer, Giovanni Traverso

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number22
DOIs
StatePublished - Jun 2 2020

ASJC Scopus subject areas

  • General

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