Etravirine is a diarylpyrimidine non-nucleoside reverse transcriptase inhibitor. Etravirine is designed to be active against HIV isolates with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs. It can bind the enzyme reverse transcriptase (RT) in multiple conformations, both for native and mutant RT, thereby blocking the enzymatic activity of RT.
Etravirine (TMC125), is highly active against wild-type HIV-1 with EC50 of 1.4 nM to 4.8 nM and shows some activity against HIV-2 with EC50 of 3.5 μM. TMC125 also inhibits a series of HIV-1 group M subtypes and circulating recombinant forms and a group O virus.  
Etravirine has a high genetic barrier to the development of resistance. TMC125 is active against HIV resistant to currently available NNRTIs, with a similar tolerability profile to that of the control group in phase IIb trials in treatment-experienced patients, including those infected with virus resistant to NNRTIs and protease inhibitors (PIs).