ViiV Healthcare presents phase III data from VIKING-3 study of dolutegravir in HIV-1 infected integrase inhibitor-resistant adults

ViiV Healthcare today announced 24-week data from the VIKING-3 Phase III study evaluating the investigational integrase inhibitor (INI) dolutegravir in HIV-1 infected adults with multiple class antiretroviral (ARV) resistance including resistance to integrase inhibitors (raltegravir and/or elvitegravir). In the study, mean HIV RNA levels declined by 1.4 log10 copies/mL after 7 days of dolutegravir 50mg twice-daily treatment was added to the current failing regimen [95% confidence interval for the difference (1.3, 1.5; p<0.001)]. The proportion of study participants who were subsequently virologically suppressed (HIV-1 RNA <50 copies/mL) with optimised background regimen (OBR) was 63% at week 24. Overall, 3% (6/183) of study participants discontinued due to adverse events. The most common drug-related adverse events were diarrhoea, nausea, and headache, each reported in 5% of subjects. These data were presented at the 11th International Congress on Drug Therapy in HIV Infection in Glasgow.

“At ViiV Healthcare we are committed to delivering treatment options for all populations of people living with HIV. VIKING-3 was designed to address a significant medical need in one of the most difficult populations to treat – those patients who have advanced disease and have developed resistance to integrase inhibitors as well as multiple other antiretroviral agents.” said John Pottage, MD, Chief Scientific and Medical Officer, ViiV Healthcare. “We are encouraged by these results in integrase inhibitor-resistant patients and look forward to receiving further phase III data in treatment-experienced patients in the coming months.”

At baseline the 183 patients enrolled in the VIKING-3 study had been on antiretroviral therapy (ART) for an average of 13 years and all had a broad range of genotypic and phenotypic resistance to integrase inhibitors (raltegravir and/or elvitegravir). In addition, 79% had resistance to ≥2 NRTIs, 75% had resistance to ≥1 NNRTI, 70% had ≥2 PI resistance-associated mutations and 61% of subjects had non-R5 HIV detected. Median baseline CD4+ counts were low at 140 cells/mL, with 56% of subjects classified as CDC Class C (patients who have one or more AIDS-defining illness). The study population included 23% women, 21% co-infected with HBV and/or HCV, and 27% of African American/African heritage.

VIKING-3 Study Design

VIKING-3 (ING112574) is a Phase III, multicentre, open-label, single arm study to assess the antiviral activity and safety of a dolutegravir containing regimen in HIV-1 infected, ART-experienced adults with historical or current evidence of resistance to integrase inhibitors (raltegravir and/or elvitegravir). VIKING-3 primary endpoints include the change at Day 8 from baseline in HIV-1 RNA with DTG 50mg BID added to the currently failing regimen (functional monotherapy) and the proportion of study participants with <50 copies/mL plus optimised background regimen (OBR) at Week 24 and beyond. Patients enrolled were required to have documented genotypic and/or phenotypic resistance to at least one drug in two or more of the other approved classes of ART but also be able to include at least one fully active drug in the OBR to be started Day 8.

About Dolutegravir and the Dolutegravir Clinical Trial Programme

S/GSK1349572 (dolutegravir, DTG) is an investigational integrase inhibitor currently in development for the treatment of HIV; it does not require an additional pharmacokinetic boosting drug to 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.

Data from the SAILING study investigating once-daily dolutegravir in treatment-experienced patients with no previous exposure to integrase inhibitors is due to be presented at upcoming scientific meetings. Data from SAILING, VIKING-3 and the previously disclosed data from the SPRING-2 and SINGLE studies will be part of global regulatory submissions for dolutegravir before the end of 2012. Dolutegravir is not yet approved as a treatment for HIV or any other indication anywhere in the world.