In a small Phase I dose-finding randomized double-blind monotherapy trial, 35 patients were randomized to placebo or to 1 of 3 dosages of S/GSK1349572, a second-generation integrase inhibitor. The patients were not on ART, had a median HIV RNA level of approximately 4.4 log10 copies/mL, and had no previous exposure to integrase inhibitors. After 10 days of treatment, HIV RNA had decreased by a mean of 1.51 to 2.46 log10 copies/mL in the 3 treatment groups (2.46 log10 copies/mL in the 50 mg once-daily group). No significant adverse effects attributable to the integrase inhibitor were noted, and no integrase resistance mutations were detected.(1)
In in vitro studies, S/GSK1349572 has shown activity against some HIV isolates with resistance to raltegravir and elvitegravir.(2)
| Clinical Bottom Line|
Based on these early data, S/GSK1349572 appears to be potent and tolerable, and may be effective against some viruses with resistance to first-generation integrase inhibitors. It is dosed once daily and requires no pharmacokinetic boosting. Enrollment will begin soon for Phase II investigations of this agent in both initial and salvage therapy.
- Lalezari J, Sloan L, Dejesus E, et al. Potent antiviral activity of S/GSK1349572, a next generation integrase inhibitor (INI), in INI-naive HIV-1-infected patients. In: Program and abstracts of the 5th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 19-22, 2009; Cape Town, South Africa. Abstract TUAB105.
- Underwood M, Johns B, Sato A, et al. S/GSK1349572: a next generation integrase inhibitor with activity against integrase inhibitor resistant clinical isolates from patients experiencing virologic failure while on raltegravir therapy. In: Program and abstracts of the 5th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 19-22, 2009; Cape Town, South Africa. Abstract WEPEA098.