A new non-nucleoside reverse transcriptase inhibitor (NNRTI), etravirine (Intelence) has received marketing approval in the European Union, manufacturer Tibotec announced last week.
Etravirine is approved for use in treatment-experienced patients in combination with a boosted protease inhibitor and other antiretroviral drugs, based on the results of the DUET studies. Etravirine received accelerated approval in the United States in January 2008, but the US licence does not specify that it should be used in combination with a boosted protease inhibitor.
DUET 1 and 2 randomised around 1200 individuals with NNRTI resistance to receive either etravirine or placebo in combination with darunavir/ritonavir (Prezista) plus at least two nucleoside analogues selected by resistance testing and treatment history (the optimised background regimen).
After 24 weeks, pooled analysis of the two studies, which were identical in design but conducted in different regions of the world, showed that significantly more patients in the etravirine study arm achieved an undetectable viral load (58.9% vs 41.1%; p3; p
Etravirine is the first NNRTI to be licensed for over ten years, and the first one to show activity in people who have already developed resistance to efavirenz (Sustiva) or nevirapine (Viramune).
Speaking in January at the time of etravirine’s US approval Dr Martin Fisher, a consultant in HIV/GU medicine at Brighton & Sussex University Hospital, said that cross-resistance to current (and possibly future) NNRTIs may be etravirine's most limiting factor. “When using etravirine one has to look very carefully at the degree of underlying non-nucleoside resistance,” he said.
“What’s become very apparent is that the more non-nucleoside mutations one has, broadly speaking, the less likely etravirine is to work. So, the critical message there is that if anybody is taking either nevirapine or efavirenz and is experiencing virological failure, you need to get off that non-nucleoside as soon as possible because otherwise you’re scuppering your chances of etravirine working in the future.”
However an analysis of patients with NNRTI resistance receiving treatment at London’s Chelsea and Westminster Hospital published earlier this year suggests that the proportion of patients who stand to benefit from etravirine despite NNRTI resistance is high. Around 90% of those who had failed treatment with either efavirenz or nevirapine showed sufficient sensitivity to etravirine to suggest that they would benefit from the drug if they received it.
The recommended oral dose of etravirine tablets is 200mg (two 100mg tablets) twice daily following a meal. Patients may also disperse the tablets in a glass of water. In the Duet studies the most frequently reported adverse events (>10%) of any intensity that occurred more frequently in patients who received etravirine were rash (17%), diarrhoea (15%) and nausea (13.9%).