Resistance

In the DUET I study analysis, according to Tibotec, 85% of participants with resistance to another NNRTI showed susceptibility to etravirine. The means of calculating this percentage has been called into question, but there is certainly a high response to this drug in treatment-experienced patients. Additionally, in contrast to other NNRTIs, more than one resistance mutation needs to develop, in order to bring about resistance to etravirine.1 2

The presence of the most common NNRTI mutation, K103N, did not affect the treatment response in individuals on etravirine in the DUET studies; however, the presence at baseline of V179D, V179F, V179T, Y181V, or G190S was associated with a decreased virologic response to etravirine.

In addition, the presence at baseline of three or more NNRTI mutations, as defined by the 2007 IAS-USA guidelines (V90I, A98G, L100I, K101E/P, K103N, V106A/I/M, V108I, V179D/F, Y181C/I/V, Y188C/H/L, G190A/S, P225H) resulted in a decreased virologic response to etravirine.

Virologic failure on an etravirine-containing regimen most commonly led to the following NNRTI-resistance associated mutations: V179F, V179I, Y181C, and Y181I. Less common emerging NNRTI-resistance associated mutations included: K101E, K103N, V106I/M, V108I, Y188L, V189I, G190S/C and R356K.3 4

Tibotec, manufacturer of etravirine, has noted that cross-resistance to efavirenz and/or nevirapine is to be expected after virologic failure while on an etravirine-containing regimen.

References

  1. Brillant JE et al. In vitro resistance development for a second-generation NNRTI: TMC125. 13th International HIV Drug Resistance Workshop, Costa Adeje, abstract 16, 2004
  2. Vingerhoets J et al. TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. J Virol 79: 12773-12782, 2005
  3. Madruga JV et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1 infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet 370: 29-38, 2007
  4. Lazzarin A et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1 infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet 370: 39-48, 2007
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