The genome of the human immunodeficiency virus (HIV) encodes three enzymes that are essential for viral replication. Of these, the integrase (IN) enzyme remains significantly underexploited as a therapeutic target although clinically, inhibition of IN has been demonstrated to reduce viral load in HIV-1-infected individuals. During the HIV replication cycle, IN catalyzes two reactions. In the first, IN binds pro-viral cDNA in the host-cell cytoplasm and catalyzes the removal of two conserved nucleotides (GT) from the 3 -ends of the long terminal repeat (LTR) strands. Following 3 processing, the pre-integration complex (PIC) is transported into the nucleus where the second reaction-strand- transfer-occurs.