Efficacy and safety of etravirine at week 96 in treatment-experienced HIV type-1-infected patients in the DUET-1 and DUET-2 trials.
BACKGROUND
Durable efficacy and long-term safety of antiretroviral therapy are important goals in the management of treatment-experienced patients. The 96-week efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine were evaluated in the Phase III DUET trials.


METHODS
HIV type-1-infected treatment-experienced adults with viral loads >5,000 copies/ml and NNRTI and protease inhibitor resistance were randomized to receive etravirine 200 mg or placebo, each twice daily and in combination with a background regimen of darunavir/ritonavir twice daily, nucleoside/nucleotide reverse transcriptase inhibitors and optional enfuvirtide. The primary end point was the proportion of patients with viral load <50 copies/ml (intent-to-treat analysis, time-to-loss of virological response algorithm) at week 24. Results from both trials were combined in the pre-specified pooled 96-week analysis.


RESULTS
In total, 599 patients received etravirine and 604 received placebo. At week 96, 57% of patients in the etravirine group versus 36% in the placebo group had a viral load <50 copies/ml (P<0.0001); 91% and 88% of patients, respectively, had maintained this response from week 48. Mean increases in CD4(+) T-cell count from baseline at week 96 were 128 cells/mm(3) with etravirine versus 86 cells/mm(3) with placebo (P<0.0001). With the exception of rash, which was reported more frequently with etravirine than placebo (21% versus 12%, respectively; P<0.0001), the safety and tolerability profile of etravirine was similar to placebo over the treatment period.


CONCLUSIONS
Etravirine, in combination with an antiretroviral background regimen, provided durable virological and immunological responses with no new safety concerns in treatment-experienced patients over 96 weeks in the DUET trials.
Université Pierre et Marie Curie, Paris 6, France. christine.katlama@psl.aphp.fr
Christine
C
Katlama
Bonaventura
B
Clotet
Anthony
A
Mills
Benoit
B
Trottier
Jean-Michel
JM
Molina
Beatriz
B
Grinsztejn
William
W
Towner
Richard
R
Haubrich
Steven
S
Nijs
Johan
J
Vingerhoets
Brian
B
Woodfall
James
J
Witek
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000069454:Darunavir; D004311:Double-Blind Method; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009570:Nitriles; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use; D011724:Pyridazines / Q000008:administration & dosage* / Q000627:therapeutic use*; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D009570:Nitriles; D010446:Peptide Fragments; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C451734:etravirine; D000077560:Enfuvirtide; D019438:Ritonavir; D000069454:Darunavir