Effectiveness

Given its activity against virus resistant to nevirapine and efavirenz, etravirine was evaluated in treatment-experienced patients in the DUET 1 and 2 studies. Its manufacturer, Tibotec, assessed etravirine combination with another of its products designed for treatment-experienced patients, the protease inhibitor darunavir (Prezista).

The phase III DUET 1 and 2 studies (identical in design, but conducted in different regions of the world) randomised 1200 individuals with at least one NNRTI resistance mutation and three or more primary PI mutations to receive either etravirine (then called TMC-125) 200mg twice daily or placebo in combination with darunavir/ritonavir plus at least two nucleoside analogues selected by resistance testing and treatment history (the optimised background regimen). Participants needed to have been on a stable regimen for at least eight weeks and have a detectable viral load above 5000 copies/ml on their current treatment regimen.1 

Significantly more patients in the etravirine than in the placebo group achieved viral load less than 50 copies/ml at week 48 (61 vs 40%). Significantly fewer patients in the etravirine group experienced at least one confirmed or probable AIDS-defining illness/death (6 vs 10%). Rash was the only adverse event to occur at a significantly higher incidence in the etravirine group (19 vs 11%), occurring primarily in the second week of treatment. Safety and tolerability in the etravirine group was comparable to the placebo group. (See the Side-effects section included in this entry for important new information on serious adverse events.)

In settings with limited access to protease inhibitors, some patients may be able to use etravirine plus two active NRTIs as second-line HAART treatment, based on genotype findings.2

Earlier small dosing and efficacy studies had already showed that etravirine could reduce viral load significantly, without serious side-effects, after one week of monotherapy.3 When added in place of a failing NNRTI, viral load fell by an average of nearly one log.4 There was no relationship between response and genotypic or phenotypic resistance, or between drug concentration and treatment response.5 6 

Despite its impressive activity against NNRTI-resistant HIV, those findings showed that the more NNRTI resistance mutations a patient has, the lower the viral load reduction. Patients with no NNRTI resistance mutations at baseline had a median viral load reduction of nearly 3 logs after 34 weeks of ETR treatment combined with an optimised background regimen. Those with three or more NNRTI mutations had a viral load reduction of less than a log. 7    

In a separate study with treatment-naive patients, etravirine monotherapy for seven days appeared to be just as potent as a combination regimen of AZT, 3TC, abacavir, indinavir, and nevirapine.8 1

References

  1. Katlama C et al. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS 23(17): 2289-300, 2009
  2. Sungkanuparph S et al. Evaluating the role of etravirine in the second-line antiretroviral therapy after failing an initial non-nucleoside reverse transcriptase inhibitor-based regimen in a resource-limited setting. Curr HIV Res 6(5): 474-476, 2008
  3. Gruzdev B et al. A randomized, double-blind, placebo-controlled trial of TMC125 as 7-day monotherapy in antiretroviral naïve, HIV-1 infected subjects. AIDS 17: 2487-2494, 2003
  4. Gazzard B et al. An open-label assessment of TMC 125 – a new, next-generation NNRTI, for 7 days in HIV-1 infected individuals with NNRTI resistance. AIDS 17: 49-54, 2003
  5. Montaner J et al. Safety and tolerability of TMC125 in 3-class-experienced HIV-infected patients: 24-week primary analysis of trial TMC125-C203. Tenth European AIDS Conference / European AIDS Clinical Society, Dublin, abstract LBPS3/7B, 2005
  6. Nadler JP et al. Efficacy and tolerability of TMC125 in HIV patients with NNRTI and PI resistance at 24 weeks: TMC125-C233. Tenth European AIDS Conference / European AIDS Clinical Society, Dublin, abstract LBPS3/7A, 2005
  7. TMC125-C223 Writing Group Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis. AIDS 21(6): F1-F10, 2007
  8. Sankatsing S et al. TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen. AIDS 17: 2623-2627, 2003
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