Abstract
HIV-1 genomic integration into host cell chromatin is a unique and pivotal step in the replication cycle of all retroviruses that is mediated by the viral integrase enzyme. For this reason, the targeting of the viral integrase enzyme that mediates this step is an attractive strategy aimed at blocking viral replication. The first integrase inhibitors to be developed entered clinical trials around 2000 and this led to regulatory approval of the first integrase strand transfer inhibitor, raltegravir, for the treatment of HIV/AIDS. Derivative second-generation integrase strand transfer inhibitors, such as dolutegravir, are now at various stages of clinical development. It is likely that dolutegravir will gain clinical licensure during 2013, whereas another new integrase strand transfer inhibitor, elvitegravir, is likely to be approved during 2012. The latter compound, however, has a very similar resistance profile to that of raltegravir. In this context, elvitegravir is unlikely to be effective in the treatment of patients who have developed resistance to raltegravir, or vice versa, whereas dolutegravir is likely to be effective in both initial therapy and in the salvage of many patients who display resistance to both raltegravir and elvitegravir.
Original language | English |
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Pages (from-to) | 697-707 |
Number of pages | 11 |
Journal | Drugs of the Future |
Volume | 37 |
Issue number | 10 |
DOIs | |
Publication status | Published - Oct 2012 |
Externally published | Yes |
Keywords
- Dolutegravir
- GSK-1349572
- HIV
- Integrase inhibitor
- S-349572