Phase 3 Study Update of Dolutegravir-based Regimen for HIV

ViiV Healthcare and Shionogi announced that initial results have been received from the Phase 3 SINGLE (ING114467) study of the investigational integrase inhibitor dolutegravir in treatment-naive adults with HIV-1.

SINGLE is an ongoing, randomized, multi-center, multinational, double-blind, double-dummy study designed to compare the efficacy and safety of two antiretroviral regimens: dolutegravir 50mg plus abacavir/lamivudine (Epzicom; GlaxoSmithKline Pharmaceuticals) vs. Atripla (tenofovir/emtricitabine/efavirenz; Bristol-Myers Squibb and Gilead). The primary endpoint was the proportion of study participants with undetectable HIV-1 RNA (<50copies/mL) at 48 weeks. As per study design, trial participants will continue on blinded therapy in order to assess the tolerability, long-term safety, and antiviral and immunologic activity of dolutegravir plus abacavir/lamivudine once-daily compared to Atripla over 96 weeks. Investigators will also evaluate viral resistance in patients experiencing virologic failure.

Four hundred fourteen treatment-naive study participants were randomized and exposed to the dolutegravir-based regimen and 419 to the Atripla arm. The study demonstrated superiority of the dolutegravir-based regimen compared to the single tablet regimen Atripla.  At 48 weeks, 88% of study participants on the dolutegravir regimen were virologically suppressed (<50 copies/mL) vs. 81% of participants on the single tablet regimen Atripla [difference and 95% CI; 7.4% (2.5%–12.3%); difference in the primary endpoint was statistically significant, P=0.003]. Differences in efficacy were primarily driven by a higher rate of discontinuation due to adverse events on the Atripla arm. The SINGLE study was designed to demonstrate non-inferiority of the dolutegravir-based regimen versus Atripla, and the primary analysis met this criterion.  Statistical superiority was concluded as part of a subsequent, pre-specified testing procedure.

Dolutegravir (S/GSK1349572) is an investigational integrase inhibitor (INI). Dolutegravir does not require an additional 'booster' drug be added to the regimen. Integrase inhibitors block HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection.

For more information call (800) 461-3696 or visit www.shionogi-inc.com.