Raltegravir: opening the road for integrase inhibitors in clinical practice

摘要

In the developed world, access to highly active antiretroviral therapy has led to a significant reduction in morbidity and mortality attributed to HIV/AIDS. However, the continual emergence of resistant HIV-1 strains and the limitations of currently available classes of antiretrovirals in terms of tolerance or toxicity highlight the need to develop agents with novel mechanisms of action. Successful completion of the HIV-1 viral life cycle requires the integration of cDNA mediated by the enzyme HIV-1 integrase, one of three essential enzymes encoded in the viral genome. Raltegravir, the first integrase inhibitor, acts specifically to block the strand transfer step. In clinical trials, raltegravir has been shown to be a potent drug with a good pharmacokinetic and side-effect profile, both in treatment-naive and -experienced patients, and has achieved high rates of virological suppression even in those with limited treatment options. Raltegravir was approved by the US FDA in October 2007 and by the European Commission in December 2007 to be used in combination therapy in previously treated HIV-1-infected individuals.