PMID- 18764771
OWN - NLM
STAT- MEDLINE
DCOM- 20090929
LR  - 20201209
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Linking)
VI  - 47
IP  - 7
DP  - 2008 Oct 1
TI  - Safety, tolerability, and preliminary efficacy of 48 weeks of etravirine therapy 
      in a phase IIb dose-ranging study involving treatment-experienced patients with 
      HIV-1 infection.
PG  - 969-78
LID - 10.1086/591705 [doi]
AB  - BACKGROUND: Etravirine (ETR; also known as TMC125) is a new nonnucleoside 
      reverse-transcriptase inhibitor with activity against wild-type and nonnucleoside 
      reverse-transcriptase inhibitor-resistant human immunodeficiency virus type 1 
      (HIV-1). METHODS: This randomized, phase IIb, placebo-controlled, 2-stage, 
      dose-escalating trial evaluated the safety, tolerability, and preliminary 
      efficacy of 3 twice-daily doses of ETR (experimental formulation TF035; compared 
      with placebo), administered with an individually optimized background regimen, in 
      treatment-experienced HIV-1-infected patients. In stage 1 of the trial, 166 
      patients received ETR (400 mg or 800 mg twice daily) or placebo. In stage 2 of 
      the trial, 74 patients received ETR (800 mg or 1200 mg twice daily) or placebo. 
      The primary objective was to assess the safety and tolerability of the regimens 
      over 48 weeks. RESULTS: Neuropsychiatric adverse events (AEs) of interest 
      occurred in 46.6% of patients in the combined ETR group and in 45.5% of patients 
      in the combined placebo group (P=.89). Clinically relevant hepatic AEs occurred 
      in 3.4% of patients who received ETR and in 6.1% of patients who received placebo 
      (P=.47), and rash occurred in 19.5% and 12.1%, respectively (P=.25). In general, 
      there was no evidence of a relationship between ETR dose and specific AEs. Most 
      AEs were severity grade 1 or 2; the incidence of grade 3 or 4 AEs was comparable 
      between groups (27.0% in the combined ETR group vs. 27.3% in the placebo group). 
      Plasma preparation tubes were used for viral load measurement. In stage 1, there 
      was no statistically significant difference in efficacy between ETR and placebo. 
      In stage 2, the decrease in log10 plasma viral load between baseline and week 24 
      was statistically significantly greater in patients who received ETR, compared 
      with patients who received placebo; a trend in favor of ETR persisted until week 
      48. CONCLUSIONS: ETR was generally safe and well tolerated during long-term 
      administration in treatment-experienced, HIV-1-infected patients, and it had a 
      safety profile comparable to that of placebo.
FAU - Montaner, Julio
AU  - Montaner J
AD  - St. Paul's Hospital, University of British Columbia, Vancouver, Canada. 
      drjm@cfenet.ubc.ca
FAU - Yeni, Patrick
AU  - Yeni P
FAU - Clumeck, Nathan N
AU  - Clumeck NN
FAU - Fatkenheuer, Gerd
AU  - Fatkenheuer G
FAU - Gatell, Jose
AU  - Gatell J
FAU - Hay, Phillip
AU  - Hay P
FAU - Seminari, Elena
AU  - Seminari E
FAU - Peeters, Monika P
AU  - Peeters MP
FAU - Scholler-Gyure, Monika
AU  - Scholler-Gyure M
FAU - Simonts, Myriam
AU  - Simonts M
FAU - Woodfall, Brian
AU  - Woodfall B
CN  - TMC125-C203 Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT00412646
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Nitriles)
RN  - 0 (Pyridazines)
RN  - 0 (Pyrimidines)
RN  - 0C50HW4FO1 (etravirine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anti-HIV Agents/administration & dosage/adverse effects/*therapeutic use
MH  - CD4 Lymphocyte Count
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - HIV Infections/*drug therapy
MH  - HIV-1
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nitriles
MH  - Pyridazines/administration & dosage/adverse effects/*therapeutic use
MH  - Pyrimidines
EDAT- 2008/09/04 09:00
MHDA- 2009/09/30 06:00
CRDT- 2008/09/04 09:00
PHST- 2008/09/04 09:00 [pubmed]
PHST- 2009/09/30 06:00 [medline]
PHST- 2008/09/04 09:00 [entrez]
AID - 10.1086/591705 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2008 Oct 1;47(7):969-78. doi: 10.1086/591705.