Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance
Integrase Strand Transfer Inhibitors (INSTIs) are currently used as the most effective therapy in the treatment of human immunodeficiency virus (HIV) infections. Raltegravir (RAL) and Elvitegravir (EVG), the first generation of INSTIs used successfully in clinical treatment, are susceptible to the e...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/12/2591 |
| _version_ | 1797454946785820672 |
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| author | Clémence Richetta Nhat Quang Tu Olivier Delelis |
| author_facet | Clémence Richetta Nhat Quang Tu Olivier Delelis |
| author_sort | Clémence Richetta |
| collection | DOAJ |
| description | Integrase Strand Transfer Inhibitors (INSTIs) are currently used as the most effective therapy in the treatment of human immunodeficiency virus (HIV) infections. Raltegravir (RAL) and Elvitegravir (EVG), the first generation of INSTIs used successfully in clinical treatment, are susceptible to the emergence of viral resistance and have a high rate of cross-resistance. To counteract these resistant mutants, second-generation INSTI drugs have been developed: Dolutegravir (DTG), Cabotegravir (CAB), and Bictegravir (BIC). However, HIV is also able to develop resistance mechanisms against the second-generation of INSTIs. This review describes the mode of action of INSTIs and then summarizes and evaluates some typical resistance mutations, such as substitution and insertion mutations. The role of unintegrated viral DNA is also discussed as a new pathway involved in conferring resistance to INSTIs. This allows us to have a more detailed understanding of HIV resistance to these inhibitors, which may contribute to the development of new INSTIs in the future. |
| first_indexed | 2024-03-09T15:44:28Z |
| format | Article |
| id | doaj.art-1c41681731fe4f8cbe0c0a5610d04af5 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T15:44:28Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-1c41681731fe4f8cbe0c0a5610d04af52023-11-24T18:36:08ZengMDPI AGViruses1999-49152022-11-011412259110.3390/v14122591Different Pathways Conferring Integrase Strand-Transfer Inhibitors ResistanceClémence Richetta0Nhat Quang Tu1Olivier Delelis2Laboratoire de Biologie et Pharmacologie Appliquée, ENS-Paris-Saclay, CNRS UMR 8113, Université Paris-Saclay, 91190 Gif-sur-Yvette, FranceLaboratoire de Biologie et Pharmacologie Appliquée, ENS-Paris-Saclay, CNRS UMR 8113, Université Paris-Saclay, 91190 Gif-sur-Yvette, FranceLaboratoire de Biologie et Pharmacologie Appliquée, ENS-Paris-Saclay, CNRS UMR 8113, Université Paris-Saclay, 91190 Gif-sur-Yvette, FranceIntegrase Strand Transfer Inhibitors (INSTIs) are currently used as the most effective therapy in the treatment of human immunodeficiency virus (HIV) infections. Raltegravir (RAL) and Elvitegravir (EVG), the first generation of INSTIs used successfully in clinical treatment, are susceptible to the emergence of viral resistance and have a high rate of cross-resistance. To counteract these resistant mutants, second-generation INSTI drugs have been developed: Dolutegravir (DTG), Cabotegravir (CAB), and Bictegravir (BIC). However, HIV is also able to develop resistance mechanisms against the second-generation of INSTIs. This review describes the mode of action of INSTIs and then summarizes and evaluates some typical resistance mutations, such as substitution and insertion mutations. The role of unintegrated viral DNA is also discussed as a new pathway involved in conferring resistance to INSTIs. This allows us to have a more detailed understanding of HIV resistance to these inhibitors, which may contribute to the development of new INSTIs in the future.https://www.mdpi.com/1999-4915/14/12/2591HIV-1strand-transfer inhibitorsintegraseunintegrated viral DNAresistance |
| spellingShingle | Clémence Richetta Nhat Quang Tu Olivier Delelis Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance Viruses HIV-1 strand-transfer inhibitors integrase unintegrated viral DNA resistance |
| title | Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance |
| title_full | Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance |
| title_fullStr | Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance |
| title_full_unstemmed | Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance |
| title_short | Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance |
| title_sort | different pathways conferring integrase strand transfer inhibitors resistance |
| topic | HIV-1 strand-transfer inhibitors integrase unintegrated viral DNA resistance |
| url | https://www.mdpi.com/1999-4915/14/12/2591 |
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