Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine
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,...
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| Format: | Article |
| Language: | English |
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National Academy of Sciences
2020
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| Online Access: | https://hdl.handle.net/1721.1/127652 |
| _version_ | 1826208658124439552 |
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| author | 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 McManus, Rebecca S Koeppen, Ryan P. Hua, Tiffany P Hayward, Alison M Collins, Joy E Tamang, Siddartha M Ishida, Keiko Miller, Jonathan B. Katz, Stephanie Slocum, Alexander H Sulkowski, Mark S. Thomas, David L. Langer, Robert S Traverso, Carlo Giovanni |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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 McManus, Rebecca S Koeppen, Ryan P. Hua, Tiffany P Hayward, Alison M Collins, Joy E Tamang, Siddartha M Ishida, Keiko Miller, Jonathan B. Katz, Stephanie Slocum, Alexander H Sulkowski, Mark S. Thomas, David L. Langer, Robert S Traverso, Carlo Giovanni |
| author_sort | Verma, Malvika |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:08:47Z |
| format | Article |
| id | mit-1721.1/127652 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:08:47Z |
| publishDate | 2020 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1276522022-10-01T19:31:30Z Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine 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 McManus, Rebecca S Koeppen, Ryan P. Hua, Tiffany P Hayward, Alison M Collins, Joy E Tamang, Siddartha M Ishida, Keiko Miller, Jonathan B. Katz, Stephanie Slocum, Alexander H Sulkowski, Mark S. Thomas, David L. Langer, Robert S Traverso, Carlo Giovanni 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 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. NIH (Grants EB000244 and 5T32DK007191-45) 2020-09-17T22:31:50Z 2020-09-17T22:31:50Z 2020-05 2020-03 2020-08-07T15:05:45Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 https://hdl.handle.net/1721.1/127652 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 en http://dx.doi.org/10.1073/pnas.2004746117 Proceedings of the National Academy of Sciences of the United States of America 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. application/pdf National Academy of Sciences PNAS |
| spellingShingle | 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 McManus, Rebecca S Koeppen, Ryan P. Hua, Tiffany P Hayward, Alison M Collins, Joy E Tamang, Siddartha M Ishida, Keiko Miller, Jonathan B. Katz, Stephanie Slocum, Alexander H Sulkowski, Mark S. Thomas, David L. Langer, Robert S Traverso, Carlo Giovanni Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine |
| title | Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine |
| title_full | Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine |
| title_fullStr | Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine |
| title_full_unstemmed | Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine |
| title_short | Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine |
| title_sort | development of a long acting direct acting antiviral system for hepatitis c virus treatment in swine |
| url | https://hdl.handle.net/1721.1/127652 |
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