5 mmol/L for etravirine and −0.6 mmol/L for placebo (Fig. 3b). There was a large difference between arms in the duration of treatment, with a median exposure of 96.0 weeks for the etravirine group and 69.6 weeks for placebo (Table 3). The frequency of AEs (regardless Barasertib of severity or causality) adjusted for treatment duration was similar between the treatment groups or lower for etravirine, with the exception of rash (Table 3). A significant difference in the frequency of rash-related AEs between treatment arms remained after adjusting for the difference in treatment exposure: 13.7 patients for etravirine vs. 9.3 patients for placebo per 100 patient-years of exposure [relative risk (95% CI) 1.48 (1.02–1.95)].

The adjusted frequency of nervous system AEs of interest was lower in the etravirine group than in the placebo group [12.6 vs. 16.8 per 100 patient-years exposure, respectively; relative risk (95% Trichostatin A in vivo CI) 0.75 (0.54–0.96)]; that of psychiatric AEs of interest was also lower [13.3 vs. 16.4 per 100 patient-years exposure, respectively; relative risk (95% CI) 0.81 (0.59–1.03)]. The findings from this week 96 pooled analysis of the DUET trials were consistent with previous results reported at weeks 24 and 48. The frequency of AEs of interest was similar in both treatment groups, with the exception of rash, which occurred more commonly in the etravirine group, in line with previous results [3, 6, 7]. These data support earlier findings

that rash events occurring in patients receiving etravirine are, however, generally mild to moderate in severity and normally resolve with continued treatment. Of note, in this analysis, there were no new discontinuations because of rash since the previous analysis at week 48.

However, with broader use of etravirine following marketing approval, severe cutaneous and hypersensitivity reactions, including ifenprodil Stevens–Johnson syndrome and toxic epidermal necrolysis, have been reported [8, 9]. As these can be life-threatening, clinical guidance requires immediate discontinuation of etravirine whenever such severe reactions are suspected [8, 9]. The findings from this week 96 analysis provide further evidence that etravirine use is not more frequently associated with neuropsychiatric AEs than placebo. Furthermore, data from the ongoing SENSE (Study of Efavirenz NeuropSychiatric Events versus Etravirine; NCT00903682) trial, comparing the week 12 frequencies of neuropsychiatric AEs in treatment-naïve, HIV-1-infected patients receiving either etravirine or efavirenz, demonstrated that etravirine has a more favourable short-term neuropsychiatric tolerability profile than efavirenz [10]. Of note, there are no comparative data for etravirine and efavirenz in treatment-experienced patients such as those enrolled in DUET, given that efavirenz would not be an appropriate comparator in this patient population because of decreased activity as a result of antiretroviral drug resistance.