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- W1574214458 abstract "Raltegravir, the first approved HIV-1 integrase inhibitor, is able to block the strand transfer step of the HIV proviral DNA integration process into the cellular host DNA. The selected dosage for the pivotal phase III studies (subsequently approved by the regulatory agencies) was 400mg bid by oral route with or without food. Raltegravir has a week effect (either inhibition or induction) on the hepatic cytochrone P450 activity. There is not need of dose adjustments in renal insufficiency or in mild-to-moderate hepatic impairment. The emerging paradigm in the field of salvage therapy was to achieve a viral load below limit of detection in almost all patients. Pretty soon it became apparent that this was feasible in more than 70-90% of patients. Raltegravir proved to be pivotal for this new paradigm. Raltegravir vs placebo both with an optimized background therapy has been tested for salvage therapy in the 005 and in the BENCHMRK studies (018 and 019). In all three studies proved to be superior to the placebo at 24, 48 and 96 weeks. Tolerance was remarkably good and virological failure was often associated with selection of integrase gene resistance mutations following the Y143C/H/R, Q148H/K/R o less frequently the NI55H paths. Finally, in the two SWITCHMRK studies non-inferiority vs Lopinavir/r could not be demonstrated in virogically suppressed patients with an stable cART containing Lopinavir/r. Most likely explanation was the presence of archived resistance mutationts to background therapy leading to a functional monotherapy with raltegravir." @default.
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- W1574214458 date "2009-11-24" @default.
- W1574214458 modified "2023-10-14" @default.
- W1574214458 title "The use of integrase inhibitors in treatment-experienced patients" @default.
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- W1574214458 doi "https://doi.org/10.1186/2047-783x-14-s3-30" @default.
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