Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence
Drug resistance prevents the successful treatment of HIV-positive individuals by decreasing viral sensitivity to a drug or a class of drugs. In addition to transmitted resistant viruses, treatment-naïve individuals can be confronted with the problem of drug resistance through de novo emergence of su...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-07-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/7/7/2790 |
| _version_ | 1818610922139156480 |
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| author | Thibault Mesplède Mark A. Wainberg |
| author_facet | Thibault Mesplède Mark A. Wainberg |
| author_sort | Thibault Mesplède |
| collection | DOAJ |
| description | Drug resistance prevents the successful treatment of HIV-positive individuals by decreasing viral sensitivity to a drug or a class of drugs. In addition to transmitted resistant viruses, treatment-naïve individuals can be confronted with the problem of drug resistance through de novo emergence of such variants. Resistant viruses have been reported for every antiretroviral drug tested so far, including the integrase strand transfer inhibitors raltegravir, elvitegravir and dolutegravir. However, de novo resistant variants against dolutegravir have been found in treatment-experienced but not in treatment-naïve individuals, a characteristic that is unique amongst antiretroviral drugs. We review here the issue of drug resistance against integrase strand transfer inhibitors as well as both pre-clinical and clinical studies that have led to the identification of the R263K mutation in integrase as a signature resistance substitution for dolutegravir. We also discuss how the topic of drug resistance against integrase strand transfer inhibitors may have relevance in regard to the nature of the HIV reservoir and possible HIV curative strategies. |
| first_indexed | 2024-12-16T15:22:07Z |
| format | Article |
| id | doaj.art-99530c1aa77e4bf193367a5f570f20fc |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-16T15:22:07Z |
| publishDate | 2015-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-99530c1aa77e4bf193367a5f570f20fc2022-12-21T22:26:36ZengMDPI AGViruses1999-49152015-07-01773703371810.3390/v7072790v7072790Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV PersistenceThibault Mesplède0Mark A. Wainberg1McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, CanadaMcGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, CanadaDrug resistance prevents the successful treatment of HIV-positive individuals by decreasing viral sensitivity to a drug or a class of drugs. In addition to transmitted resistant viruses, treatment-naïve individuals can be confronted with the problem of drug resistance through de novo emergence of such variants. Resistant viruses have been reported for every antiretroviral drug tested so far, including the integrase strand transfer inhibitors raltegravir, elvitegravir and dolutegravir. However, de novo resistant variants against dolutegravir have been found in treatment-experienced but not in treatment-naïve individuals, a characteristic that is unique amongst antiretroviral drugs. We review here the issue of drug resistance against integrase strand transfer inhibitors as well as both pre-clinical and clinical studies that have led to the identification of the R263K mutation in integrase as a signature resistance substitution for dolutegravir. We also discuss how the topic of drug resistance against integrase strand transfer inhibitors may have relevance in regard to the nature of the HIV reservoir and possible HIV curative strategies.http://www.mdpi.com/1999-4915/7/7/2790HIVintegrase strand-transfer inhibitorsresistanceraltegravirelvitegravirdolutegravirR263Kviral fitnessviral reservoirsHIV eradication |
| spellingShingle | Thibault Mesplède Mark A. Wainberg Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence Viruses HIV integrase strand-transfer inhibitors resistance raltegravir elvitegravir dolutegravir R263K viral fitness viral reservoirs HIV eradication |
| title | Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence |
| title_full | Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence |
| title_fullStr | Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence |
| title_full_unstemmed | Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence |
| title_short | Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence |
| title_sort | resistance against integrase strand transfer inhibitors and relevance to hiv persistence |
| topic | HIV integrase strand-transfer inhibitors resistance raltegravir elvitegravir dolutegravir R263K viral fitness viral reservoirs HIV eradication |
| url | http://www.mdpi.com/1999-4915/7/7/2790 |
| work_keys_str_mv | AT thibaultmesplede resistanceagainstintegrasestrandtransferinhibitorsandrelevancetohivpersistence AT markawainberg resistanceagainstintegrasestrandtransferinhibitorsandrelevancetohivpersistence |