title: Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis.
abstract: OBJECTIVE
  TMC125-C223 is an open-label, partially blinded, randomized clinical trial to evaluate the efficacy and safety of two dosages of etravirine (TMC125), a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant HIV-1.
  
  
  METHODS
  A total of 199 patients were randomly assigned 2: 2: 1 to twice-daily etravirine 400 mg, 800 mg and control groups, respectively. The primary endpoint was a change in viral load from baseline at week 24 in the intention-to-treat population.
  
  
  METHODS
  Patients had HIV-1 with genotypic resistance to approved NNRTIs and at least three primary protease inhibitor (PI) mutations. Etravirine groups received an optimized background of at least two approved antiretroviral agents [nucleoside reverse transcriptase inhibitors (NRTI) and/or lopinavir/ritonavir and/or enfuvirtide]. Control patients received optimized regimens of at least three antiretroviral agents (NRTIs or PIs and/or enfuvirtide).
  
  
  RESULTS
  The mean change from baseline in HIV-1 RNA at week 24 was -1.04, -1.18 and -0.19 log10 copies/ml for etravirine 400 mg twice a day, 800 mg twice a day and the control group, respectively (P < 0.05 for both etravirine groups versus control). Etravirine showed no dose-related effects on safety and tolerability. No consistent pattern of neuropsychiatric symptoms was observed. There were few hepatic adverse events, and rashes were predominantly early onset and mild to moderate in severity.
  
  
  CONCLUSIONS
  Etravirine plus an optimized background significantly reduced HIV-1-RNA levels from baseline after 24 weeks in patients with substantial NNRTI and PI resistance, and demonstrated a favorable safety profile compared with control.
authors.affiliation: Hillsborough County Health Department, University of South Florida, Tampa, FL 33602, USA. jpnadler@gmail.com
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Nadler
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Berger
authors.forename: Gary
authors.initials: G
authors.lastname: Blick
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Cimoch
authors.forename: Calvin J
authors.initials: CJ
authors.lastname: Cohen
authors.forename: Richard N
authors.initials: RN
authors.lastname: Greenberg
authors.forename: Charles B
authors.initials: CB
authors.lastname: Hicks
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Iveson
authors.forename: Dushyantha S
authors.initials: DS
authors.lastname: Jayaweera
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Mills
authors.forename: Monika P
authors.initials: MP
authors.lastname: Peeters
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ruane
authors.forename: Peter
authors.initials: P
authors.lastname: Shalit
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Schrader
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Smith
authors.forename: Corklin R
authors.initials: CR
authors.lastname: Steinhart
authors.forename: Melanie
authors.initials: M
authors.lastname: Thompson
authors.forename: Johan H
authors.initials: JH
authors.lastname: Vingerhoets
authors.forename: Ellen
authors.initials: E
authors.lastname: Voorspoels
authors.forename: Douglas
authors.initials: D
authors.lastname: Ward
authors.forename: Brian
authors.initials: B
authors.lastname: Woodfall
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D004325:Dreams / Q000187:drug effects; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000139:chemically induced; D009154:Mutation; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine