We report the results from further analyses investigating the frequency, time distribution and severity of AEs

and laboratory abnormalities of interest for etravirine, performed using the week 96 data set from the DUET trials. For these analyses, AEs of interest were selected based on their relevance in the target population (i.e. treatment-experienced, HIV-1-infected patients), their known association with other antiretrovirals and their potential importance based on preclinical or earlier clinical data. We also present the frequency of AEs and laboratory abnormalities per 100 patient-years of exposure for all AEs and laboratory abnormalities of interest to account buy Metformin for the difference in extent of exposure between the etravirine and placebo groups. DUET-1 (NCT00254046) and DUET-2 (NCT00255099) were randomized, double-blind, placebo-controlled, phase III trials of 48 weeks’ duration, with an optional open-label 48-week extension period. Patients were randomized to receive etravirine 200 mg twice daily (bid) or placebo, both in combination with a background regimen of darunavir/ritonavir 600/100 mg bid, investigator-selected nucleoside

reverse transcriptase inhibitors and optional PI3K activity enfuvirtide. The DUET trial design and methodology have been previously reported in detail [3, 6, 7]. Treatment-experienced, HIV-1-infected patients with plasma viral load > 5000 HIV-1 RNA copies/mL were enrolled if they had been on stable therapy for ≥ 8 weeks, had at least one NNRTI resistance-associated mutation (RAM) and at least three primary PTK6 protease inhibitor mutations at screening or in documented historical genotype. The trial protocols were reviewed and approved by the relevant Independent Ethics Committees or Institutional Review Boards,

and written informed consent was obtained from all participants prior to any trial-related procedures. The trials were conducted according to the principles of good clinical practice, the Declaration of Helsinki and the European Union Clinical Trials Directive. The week 96 pooled analysis of DUET-1 and DUET-2 was pre-specified. Safety assessments were carried out every 8 weeks between week 48 and week 96. For the purposes of this analysis, AEs of interest (and preferred terms) were: nervous system AEs (e.g. headache, dizziness, somnolence, memory impairment, amnesia, disturbance in attention, balance disorder, and restless legs syndrome); psychiatric AEs (e.g. depression, insomnia, anxiety, sleep disorder, libido decreased, abnormal dreams, stress, confusional state, nightmare and panic attack); rash-related AEs (e.g.