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DUET-2: Week-48 Results of a Phase III Randomized Double-blind Trial to Evaluate the Efficacy and Safety of TMC125 vs Placebo in 591 Treatment-experienced HIV-1-infected Patients
Margaret Johnson*1, T Campbell2, B Clotet3, C Katlama4, A Lazzarin5, W Towner6, M Peeters7, J Vingerhoets7, S Bollen7, G De Smedt7, and on behalf of the DUET-2 study group
1Royal Free Hosp, London, UK; 2Univ of Colorado Hlth Sci Ctr, Denver, US; 3Hosp Unive Germans Trias i Pujol and irsiCaixa Fndn, Barcelona, Spain; 4Hosp Pitie-Salpetriere, Paris, France; 5San Raffaele Univ, Milan, Italy; 6Kaiser Permanente, Los Angeles, CA, US; and 7Tibotec BVBA, Mechelen, Belgium
Background: The week-24 primary
analysis of DUET-2 showed that TMC125 (etravirine, ETR), a next-generation
NNRTI, provides strong antiviral activity and a good tolerability profile in
treatment-experienced patients with HIV-1. We present a pre-planned analysis of
week 48 efficacy and safety data.
Methods: DUET-2 is an ongoing 96-week
randomized, double-blind phase III trial designed to show superiority of TMC125
200 mg vs placebo, both given twice-daily with a background regimen of
darunavir/ritonavir (DRV/r), investigator-selected NRTI and optional
enfuvirtide (ENF), in patients with documented NNRTI resistance and ³3 primary protease
inhibitor (PI) mutations (November 2005, IAS-USA list). The primary endpoint
was the percentage of patients with confirmed viral load <50 copies/mL at week
24 (TLOVR). Safety was assessed throughout the study.
Results: The intent-to-treat population
included 591 patients (median baseline viral load 4.8 log10 copies/mL;
CD4 count 105 cells/mm3, 55% CDC Category C, median NNRTI mutations
2, 27% used ENF de novo).
Of patients with viral load <50 copies/mL
at week 24, 90% of patients maintained viral load <50 copies/mL at week 48
with TMC125 + background regimen vs 88% with placebo + background regimen.
Furthermore, a significantly increased mean CD4 cell count was observed at week
48 with TMC125 + background regimen vs placebo + background regimen. Similar to
week 24, Week 48 safety data showed that the incidence and severity of adverse
events with TMC125 were similar to placebo: any adverse events (95.6% TMC125
vs 95.3% placebo), serious adverse events (20.7% vs 22.0%), grade-3 or -4 adverse
events (38.0% vs 34.1%), adverse events leading to discontinuation (7.8% vs
4.4%). The most common adverse events were diarrhea (22.0% vs 22.6%), rash (any
type) (16.6% vs 11.1%), and nausea (14.6% vs 10.8%). Most rashes were mild to
moderate, infrequently led to discontinuation (2.4% vs 0%), occurred early and
resolved with continued treatment. The incidences of nervous system (16.6% vs
17.9%) and psychiatric disorders (20.0% vs 20.9%) with TMC125 were comparable
to placebo.
Conclusions: At 48 weeks, in
treatment-experienced patients with documented NNRTI resistance, TMC125
+ background regimen provided durable and superior virologic
and immunologic benefits vs placebo + background regimen. TMC125 was well
tolerated and adverse events were mostly similar to placebo with no new safety
concerns.
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