GSK-572

S/GSK1349572, or GSK-572 for short, is a second-generation integrase inhibitor being developed jointly by Shionogi of Japan and ViiV Healthcare.

Laboratory and early clinical studies showed that GSK-572 strongly inhibits HIV, has good oral bioavailability when taken once daily without a pharmacoenhancer or 'booster', and appears to have a high genetic barrier to resistance.

GSK-572 has continued to show potent antiviral activity – including activity against HIV strains resistant to raltegravir (Isentress) – in the SPRING-1 study and the VIKING trial.

SPRING-1 is an ongoing, multicentre phase IIb trial comparing 10mg, 25mg or 50mg of GSK-572 to 600mg efavirenz (Sustiva) once daily in previously untreated individuals, alongside a dual-nucleoside backbone.¹ An interim 16-week analysis showed "rapid and robust" antiviral activity at all doses; 96% of participants in the 10mg arm, 92% in the 25mg arm and 90% in the 50mg arm achieved viral load below 50 copies/ml, compared with 60% in the efavirenz arm. Participants taking GSK-572 took a significantly shorter time to reach undetectable viral load than those taking efavirenz.

GSK-572 was generally well-tolerated. Between 4 and 8% of participants taking GSK-572 experienced at least moderate side-effects, compared with 18% taking efavirenz. Gastrointestinal symptoms were the most common type of side-effect among GSK-572 recipients. No one taking the experimental drug had any serious drug-related adverse events. Serious laboratory abnormalities were rare across the board.

VIKING is an open-label, single-arm phase IIb study looking at the safety and efficacy of GSK-572 in 27 treatment-experienced participants with pre-existing resistance to raltegravir, as well as resistance to any three classes of antiretroviral drugs.² Participants first took 50mg GSK-572 once daily as the only active drug in their regimen for 10 days. Their background regimen was then optimised and they continued on treatment through 24 weeks.

People who had developed the Q148 raltegravir resistance mutation plus secondary changes showed reduced susceptibility to GSK-572, whilst those with other major raltegravir resistance mutations – either Q148 alone or mutations in the N155 or Y143 pathways – showed little or no decrease in GSK-572 activity.

Overall, 78% of participants reached a viral load below 400 copies/ml by day 11, or at least a 0.7 log drop in HIV RNA (average decrease 1.45 log). But response differed substantially based on type of pre-existing resistance. Just 33% of patients with Q148 plus secondary mutations achieved viral suppression (mean decrease 0.72 log) compared with all participants who had N155 and Y143 mutations (mean decrease 1.82 log).