Integration is a key step in the HIV-1 life cycle in which the ends of linear viral DNA are covalently joined with host chromosomal DNA. Integrase is the highly conserved and essential viral protein that performs two catalytically related reactions that ultimately lead to the insertion of the viral genome into that of the host cell. The only chemotherapeutic agents against integrase currently available for HIV-1 infected individuals are those that interrupt strand transfer, the second step of catalysis. Accordingly, this article outlines possible future strategies targeting the first catalytic step, 3' processing, as well as other nonenzymatic, yet indispensible, functions thought to be co-ordinated by integrase. Importantly, the interruption of irremediable recombination between viral and host DNAs represents the last step after viral entry at which an otherwise irreversible infection can be prevented.
