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.