Unlike other nonnucleoside
reverse transcriptase inhibitors,
etravirine is only approved for use in treatment-experienced patients. In the DUET 1 and 2 trials, 1203 highly treatment-experienced patients were randomized to
etravirine or placebo, in combination with
darunavir/
ritonavir and optimized background treatment. In these trials,
etravirine showed significantly higher rates of HIV
RNA suppression when compared with placebo (61% versus 40% at Week 48). There was no significant rise of
lipids or neuropsychiatric adverse events, but there was an increase in the risk of
rash with
etravirine treatment. In the SENSE trial, which evaluated
etravirine and
efavirenz in 157 treatment-naïve patients in combination with 2
nucleoside analogues, there was a lower risk of
lipid elevations and neuropsychiatric adverse events with
etravirine when compared to
efavirenz.
Etravirine has been evaluated in three randomized switching studies. In the SSAT029 switch trial, 38 patients who had neuropsychiatric adverse events possibly related to
efavirenz showed an improvement in these after switching to
etravirine. The Swiss Switch-EE recruited 58 individuals without neuropsychiatric adverse events who were receiving
efavirenz, and no benefit was shown when switching to
etravirine. In the Spanish ETRA-SWITCH trial (n = 46), there were improvements in
lipids when individuals switched from a
protease inhibitor to
etravirine. These switching trials were conducted in patients with full HIV
RNA suppression: <50 copies/mL and with no history of virological failure or resistance to
therapy. The results from these three randomized switching studies suggest a possible new role for
etravirine, in combination with two
nucleoside analogues, as a switching option for those with HIV
RNA suppression but who are reporting adverse events possibly related to antiretroviral
therapy. However a large well-powered trial would need to be conducted to strengthen the evidence from the pilot studies conducted so far.