Investigational Integrase Inhibitor Shows Potent Activity in Early Studies

HIV Meds Quarterly Research Brief, Summer 2009

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 log ₁₀ 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 log ₁₀ copies/mL in the 3 treatment groups (2.46 log ₁₀ 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.

References

1. 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.
2. 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.

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