Which mutations cause resistance to etravirine in antiretroviral therapy of HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Etravirine has a higher genetic barrier to resistance than other currently available NNRTIs. A single mutation at 103 or 181 is insufficient to cause clinical failure of etravirine. [31] Clinical trials have identified 17 resistance mutations associated with decreased response to etravirine: V90I, A98G, L100I, K101E, K101H, K101P, V106I, E138A, V179D, V179F, V179T, Y181C, Y181I, Y181V, G190A, G190S, and M230L. [32]

A 2008 study found that different mutations affect viral susceptibility to etravirine to varying degrees. Each etravirine resistance-associated mutation was assigned a relative weight. The virologic response was found to be a function of the number and weight of resistance mutations. With a cumulative score of 0-2, a response rate of 74% was reported. With a score of 2.5-3.5 or 4 or more, response rates of 52% and 38%, respectively, were reported. [32]

The etravirine mutation weighting scheme is as follows [32] :

  • 3 - Y181I, Y181V

  • 2.5 - L100I, K101P, Y181C, M230L

  • 1.5 - V106I, E138A, V179F, G190S

  • 1 - V90I, A98G, K101E, K101H, V179D, V179T, G190A

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