Coverage of 2006 International
Conference on AIDS

August 14–18, 2006, Toronto, Canada

 

Mixed Results for Next Generation NNRTI

Paul Dalton, Treatment Advocate, Project Inform
August 16, 2006

Dr. Cal Cohen presented data on Tibotec’s second generation non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (formerly known as TMC-125) at the 2006 International Conference on AIDS in Toronto, Ontario, Canada. The study, called TMC-215C223, compared two doses of etravirine (400mg and 800mg both twice a day) together with a potent anti-HIV regimen (or, optimized background therapy) to a potent regimen that didn’t include etravirine.

While most people (39 of 40) taking only the optimized background stopped during the trial—mostly due to increases in HIV levels while on therapy—less than 10% of people taking etravirine regimens with etravirine experienced rebounds in HIV levels. This is a hopeful finding.

Less impressive were the numbers of people able to achieve robust reductions in viral load. Among people taking the regimen with 400mg of etravirine twice daily, only 23% had viral loads below 50 copies after 48 weeks. The higher dose group—those taking 800mg of etravirine twice a day—had similar results, with 22% achieving viral suppression to below 50.

Digging a bit deeper it seems that people who had the least evidence of NNRTI resistance (fewer resistance mutations) had the largest drops in viral load. People with a single point mutation taking 800mg twice daily of etravirine experienced an impressive 1.67 log reduction in viral load, while people with two mutations achieved a drop of 1.38 logs. People with more than three mutations only experienced a modest 0.54 log drop. These results suggest that etravirine will be most useful for people with only limited NNRTI experience, and of less use for people with NNRTI resistance.

The company has chosen the 800mg twice daily dose to move forward with its phase III program, which is currently in progress. The company expects to file for approval for this drug sometime in 2007. It will be available through an expanded access program before approval, possibly as early as late 2006.

People with HIV are in need of a new NNRTI—there can be little doubt about that. The three currently available drugs in this class are so highly cross-resistant that most people only get a single chance at this potent class of anti-HIV drugs. Earlier research on etravirine had activists hoping for an even more potent drug than it appears to be.

The company developing etravirine, Tibotec, has a follow-up compound called TMC-278 currently in phase II studies. Early data suggest it might be more potent than etravirine, although it is too soon to say. People whose virus rebounds on etravirine are unlikely to respond well to TMC-278.