TY - JOUR
T1 - Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine
AU - Verma, Malvika
AU - Chu, Jacqueline N.
AU - Salama, John A.F.
AU - Faiz, Mohammed T.
AU - Eweje, Feyisope
AU - Gwynne, Declan
AU - Lopes, Aaron
AU - Hess, Kaitlyn
AU - Soares, Vance
AU - Steiger, Christoph
AU - McManus, Rebecca
AU - Koeppen, Ryan
AU - Hua, Tiffany
AU - Hayward, Alison
AU - Collins, Joy
AU - Tamang, Siddartha M.
AU - Ishida, Keiko
AU - Miller, Jonathan B.
AU - Katz, Stephanie
AU - Slocum, Alexander H.
AU - Sulkowski, Mark S.
AU - Thomas, David L.
AU - Langer, Robert
AU - Traverso, Giovanni
N1 - Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
PY - 2020/6/2
Y1 - 2020/6/2
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.2004746117
DO - 10.1073/pnas.2004746117
M3 - Article
C2 - 32424082
AN - SCOPUS:85085904720
SN - 0027-8424
VL - 117
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 22
ER -