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Etravirine demonstrates a favourable safety and tolerability profile: pooled 96-week results from the Phase III DUET trials
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Reported by Jules Levin EACS Nov 3 2009, Cologne, Germany
Pierre-Marie Girard,1 Beatriz Grinsztejn,2 Anne Rachline,3 Steven Nijs,4 James Witek5
1Hopital St Antoine, Paris, France; 2Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil; 3Hopital Saint-Louis, Paris, France;
4Tibotec BVBA, Mechelen, Belgium; 5Tibotec Inc., Yardley, PA,
ABSTRACT
Background
The next-generation NNRTI etravirine (ETR; TMC125) demonstrated superior efficacy versus placebo, and a tolerability profile generally similar to placebo, at Weeks 24 and 48 in treatment-experienced, HIV-1-infected patients enrolled in the Phase III DUET trials. We report Week 96 safety results from a prespecified pooled analysis of the DUET-1 and DUET-2 trials.
Methods
Patients with documented NNRTI resistance and ≥3 primary protease inhibitor (PI) mutations were randomized to ETR 200mg or placebo bid, both with a background regimen (BR) of darunavir with low-dose ritonavir (DRV/r), investigator-selected NRTI(s) ± enfuvirtide (ENF). Incidence and severity of adverse events (AEs) were recorded. To account for the difference in treatment duration, incidences were adjusted for total patient years of exposure.
Conclusions
Consistent with previous results at 24 and 48 weeks, overall rates of AEs were similar between both arms, with the exception of rash which occurred more commonly with ETR treatment. The incidence of AEs adjusted for patient exposure was similar and often lower in the ETR + BR group than the placebo + BR group. Except for rash, ETR + BR demonstrates a tolerability profile similar to placebo over 96 weeks in the DUET trials.
Results
Five hundred and ninety-nine and 604 patients were randomised to ETR + BR and placebo + BR, respectively. Median treatment duration was 96 vs 70 weeks. The incidence of AEs with ETR + BR was generally comparable to placebo + BR, with the exception of rash. No significant increase in rash occurred from Week 48 to 96 and the incidence of nervous system, psychiatric, and hepatic AEs, and grade 3/4 lipid abnormalities was generally comparable between treatment groups. When adjusted for total patient years of exposure, the incidence of any
AE, grade 3/4 AE, serious AE (SAE), AEs leading to discontinuation, death, nervous system and psychiatric AEs, hepatic AEs and lipid abnormalities was similar between the treatment groups.
PYE = patient years of exposure; AST = aspartate aminotransferase; ALT = alanine aminotransferase; LDL = low-density lipoprotein;
*p<0.0001 vs placebo; Grade 4, likely related to an allergic reaction to trimethoprim/sulfamethoxazole; p=0.3140 vs placebo;
p=0.7204 vs placebo; #p=0.3370 vs placebo. All p values were determined by Fisher's exact test
Conclusions
Consistent with previous results at 24 and 48 weeks, overall rates of AEs were similar between both arms, with the exception of rash which occurred more commonly with ETR treatment. The incidence of AEs adjusted for patient exposure was similar and often lower in the ETR + BR group than the placebo + BR group. Except for rash, ETR + BR demonstrates a tolerability profile similar to placebo over 96 weeks in the DUET trials.
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