GSK-1349572, a novel integrase inhibitor for the treatment of HIV infection.

GSK-1349572 (S/GSK-1349572), under development by ViiV Healthcare and Shionogi & Co Ltd, is the lead from a series of HIV integrase inhibitors, for the potential oral treatment of HIV infection. Initial evaluation of the drug in an in vitro integrase strand assay demonstrated specific inhibition of recombinant integrase. Inhibition of the integrase strand transfer reaction by GSK-1349572 was later confirmed in a cell-based assay, and the drug also displayed in vitro activity against integrase-resistant clinical isolates from patients experiencing virological failure while receiving raltegravir. The pharmacokinetic profile of GSK-1349572 supports once-daily dosing without the requirement for boosting with ritonavir. In phase I and II clinical trials, in healthy volunteers and in patients with HIV-1 infection, side effects of GSK-1349572 were generally similar to placebo; no consistent relationship was observed between the frequency of adverse events and either the dose or duration of treatment with GSK-1349572. At the time of publication, phase IIb trials of GSK-1349572 were ongoing in antiretroviral-naïve and -experienced patients. With the high demand for second-generation integrase inhibitors for antiretroviral-experienced patients and for once-daily drugs without ritonavir-boosting for treatment-naïve patients, this second-generation integrase inhibitor has the potential to become a highly valued product.