Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis.
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.
Hillsborough County Health Department, University of South Florida, Tampa, FL 33602, USA. jpnadler@gmail.com
Nadler
Jeffrey P
JP
Berger
Daniel S
DS
Blick
Gary
G
Cimoch
Paul J
PJ
Cohen
Calvin J
CJ
Greenberg
Richard N
RN
Hicks
Charles B
CB
Hoetelmans
Richard M W
RM
Iveson
Kathy J
KJ
Jayaweera
Dushyantha S
DS
Mills
Anthony M
AM
Peeters
Monika P
MP
Ruane
Peter J
PJ
Shalit
Peter
P
Schrader
Shannon R
SR
Smith
Stephen M
SM
Steinhart
Corklin R
CR
Thompson
Melanie
M
Vingerhoets
Johan H
JH
Voorspoels
Ellen
E
Ward
Douglas
D
Woodfall
Brian
B
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
D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine