Etravirine (Intelence)

Etravirine (Intelence) is an anti-HIV drug that reduces the amount of virus in the body and belongs to the class of drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). The enzyme reverse transcriptase converts single-stranded viral RNA into DNA. Drugs in the NNRTI class stop HIV from replicating within cells by binding near reverse transcriptase’s active site and inhibiting polymerase activity.

Etravirine is the first NNRTI to be licensed since 1998 and the first one to show activity in people who have already developed resistance to efavirenz (Sustiva) or nevirapine (Viramune).1  Formerly known as TMC-125, etravirine was developed by Tibotec Pharmaceuticals, Ltd. and is a diarylpyrimidine (DAPY), a different type of NNRTI specifically designed to be less susceptible than other NNRTIs to resistance mutations. As a flexible molecule, it can fit into different shaped binding pockets in the reverse transcriptase enzyme and this is why it remains active against HIV that is resistant to other NNRTIs.2 

Etravirine is indicated for treatment-experienced adults who have evidence of viral replication and HIV strains resistant to an NNRTI and other antiretrovirals. It should not be combined with licensed nucleoside analogues alone, due to the the risk of virologic failure.

Etravirine is not recommended for use with an unboosted protease inhibitor, ritonavir-boosted atazanavir, fosamprenavir, or tipranavir. In addition, the manufacturer recommends resistance testing before initiating therapy with this drug.

Etravirine was approved in the US and European Union in 2008.

References

  1. Andries K et al. TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 48: 4680-4686, 2004
  2. Das K et al. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J Med Chem 47: 2550-2560, 2004