Integrase strand transfer inhibitors are one of the newest class of antiretroviral drugs. This class of drugs inhibit the catalytic activity of HIV-1 integrase, an HIV-1-encoded enzyme required for viral replication [1]. Inhibition of integrase prevents covalent insertion of unintegrated, linear HIV-1 DNA into the host cell genome, therefore preventing the formation of HIV-1 provirus. RAL, the first agent in its class, was initially approved in 2007 for use in patients harboring drug-resistant HIV [2]. More recently, the FDA has expanded the indication for RAL use in HIV-infected patients who are antiretroviral naïve [3]. The currently approved dose is 400 mg twice daily. The RAL area-under-the-curve (AUC) and Cmax increase in a dose-dependent fashion over the range of 100 mg to 1,600 mg. With twice-daily dosing, PK steady state is achieved within approximately the first 2 days. Considerable variability was observed in the PK of raltegravir in clinical trials. In clinical trial participants receiving twice-daily RAL 400 mg, drug exposures were characterized by a geometric mean AUC within the first 12 hours of 14.3 mcM(hr) and a plasma concentration at 12 hours of 142 nM [3]. RAL at concentrations of 6 to 50 nM resulted in 95% inhibition (EC95) of viral spread in mitogen-activated human peripheral blood mononuclear cells (PBMCs) infected with diverse, primary clinical isolates of HIV-1, including isolates resistant to reverse transcriptase inhibitors and protease inhibitors (PIs).