Among the potential new classes of antiretroviral therapies thought to overcome problems with tolerability and the emergence of viral resistance, are HIV maturation and integrase inhibitors. While the specific interactions responsible for activity of he first-in-class maturation inhibitor bevirimat have yet to be fully characterized, it is clear that the target for bevirimat is the Gag polyprotein precursor, the main structural protein responsible for assembly and budding of virion particles. Clinical development is progressing, with demonstration of both safety and efficacy in early-stage trials. These encouraging results, coupled with the discovery and development of future generations of maturation inhibitors, suggest that maturation inhibitors may be added to the growing set of tools available to control HIV/AIDS. The enzyme HIV integrase is one of three essential enzymes encoded in the viral genome. It catalyzes the insertion of the proviral DNA into the host genome (strand transfer) and, thus, has a crucial role in viral replication. Moreover, it has no cellular homologue in humans and, therefore, presents an attractive drug target. HIV integrase inhibitors are on the verge of realization with the first-in-class drug raltegravir under regulatory review. The results from preclinical and clinical studies on the first generation integraase inhibitors reiterate a demand for novel second generation inhibitors with improved pharmacokinetic and metabolic properties. A number of molecules are under investigation.

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