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GSK572 Integrase Inhibitor Shines In Phase II

By Liz Highleyman

Summer/Fall 2010

S/GSK1349572 -- or GSK572 for short -- is a second-generation integrase inhibitor being developed jointly by Shionogi and ViiV Healthcare. Prior research has shown that it works against HIV with some raltegravir-resistance mutations and has a high genetic barrier to resistance. According to data from two Phase IIb trials presented at AIDS 2010, the drug continues to demonstrate potent antiviral activity and good tolerability.

The SPRING-1 study (abstract THLBB205) included 205 previously untreated HIV patients. Most were men, 80% were white, and the median baseline CD4 cell count was 324 cells/mm3. Participants were randomly assigned to receive GSK572 at doses of 10 mg, 25 mg, or 50 mg, or else 600 mg efavirenz once-daily. About two-thirds took tenofovir/emtricitabine and one-third took abacavir/lamivudine as an NRTI backbone.

In a planned 16-week interim analysis, GSK572 demonstrated "rapid and robust" antiviral activity, with at least 90% of participants in all three dose arms reaching undetectable HIV RNA (below 50 copies/mL), compared with 60% in the efavirenz arm. Patients using GSK572 also took significantly less time to achieve viral suppression. CD4 cell gains ranged from 153 to 176 cells/mm3 in the GSK572 arms, compared with 116 cells/mm3 in the efavirenz arm.

GSK572 was generally well-tolerated; only 4%-8% of participants in the GSK572 arms experienced at least moderate drug-related adverse events, compared with 18% in the efavirenz arm.

VIKING was a smaller single-arm trial evaluating the safety and efficacy of GSK572 in 27 treatment-experienced patients, again mostly men, with pre-existing resistance to raltegravir (Isentress) and to any three antiretroviral drug classes (abstract MOAB0105). Participants in this study had more advanced HIV disease -- with a median CD4 cell count of 110 cells/mm3 and about 60% with a diagnosis of AIDS -- and they had been on ART for a median of 14 years and taken a median of 17 drugs.

All participants first received 50 mg once-daily GSK572 as "functional monotherapy" (i.e., the only active drug) for 10 days, then background regimens were optimized and treatment continued through week 24. Overall, 78% of study participants achieved viral load below 400 copies/mL by day 11, with a mean HIV RNA drop of 1.45 log. But response differed according to pre-existing resistance. Just 33% of people with a Q148 mutation plus at least one secondary mutation achieved virological response, compared with all patients with N155 and Y143 mutations. Again, GSK572 was generally well-tolerated with no serious drug-related adverse events.

In October, Shionogi-ViiV announced the start of the GSK57 Phase III development program, including the SPRING-2 trial enrolling treatment-naive participants and the SAILING study enrolling treatment-experienced patients.

Liz Highleyman ( is a freelance medical writer based in San Francisco.

This article was provided by San Francisco AIDS Foundation. It is a part of the publication Bulletin of Experimental Treatments for AIDS. You can find this article online by typing this address into your Web browser:

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