Coverage of 2007 IAS
(International AIDS Society)

July 2007, Sydney, Australia

Two Studies Report Data on Etravirine

July 26, 2007

Pivotal data were presented on the experimental NNRTI etravirine (TMC-125) at the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Etravirine is the first drug of its type to work against HIV that has grown resistant to other NNRTIs, like Sustiva (efavirenz) and Viramune (nevirapine).

The DUET-1 and DUET-2 trials compared etravirine to a placebo in people with extensive experience taking HIV drugs and documented resistance to NNRTIs. Everyone in the study took a background combination of anti-HIV drugs contaning the boosted protease inhibitor Prezista (darunavir + ritonavir).

After 48 weeks significantly more people taking etravirine in both studies had HIV levels below 50 copies. In DUET 1, 56% of people taking etravirine had HIV levels below 50 copies compared to 39% of people taking the placebo (62% vs. 44% in DUET 2). On average people taking etravirine experienced reductions in HIV levels or around 2.3–2.4 logs, compared to 1.7 logs for people taking the placebo. CD4 cell counts rose on average of 78–89 for people taking etravirine, compared to 64–66 for people in taking the placebo.

Not surprisingly the more active drugs that people were taking in the study, the better their results. People who had no additional active drugs in their regimen, 44–47% taking etravirine had HIV levels below 50 copies, compared to 7–9% on the placebo. The difference grew smaller as more active drugs were available, but etravirine still appeared to add benefit.

Etravirine also appears to work best against HIV that has fewer NNRTI associated mutations. If one or fewer NNRTI mutations were detected at baseline, 60–75% of people taking etravirine achieve HIV levels below 50 copies. If three NNRTI mutations were present, that number dropped to 45%; with 4 down to 25%. When five NNRTI mutations were detected, only 15% of people achieved HIV levels below 50 copies.

The most common side effect associated with etravirine in the DUET studies was rash, which occurred in about 17% of people in the two studies. Most rashes were mild to moderate, and rarely (2%) led people to stop taking their treatment. Rash was more common in women, but no association with CD4 count was seen.

These are promising results for people who can no longer take NNRTIs due to resistance. The three currently available NNRTIs are highly cross-resistant, meaning that HIV that has grown resistant to one drug is likely to be resistant to the others. This has meant that most people have only had one shot at this powerful class of anti-HIV drugs. The development of an effective and well tolerated, second generation NNRTI is therefore a welcome development.