Etravirine effective at HIV supression: DUET trials 1 and 2

Treatment with TMC125 (etravirine) leads to better virological suppression than placebo as part of antiretroviral therapy in patients with documented resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), conclude two randomised trials in this week's issue of The Lancet.

TMC125 is a well tolerated new NNRTI with activity against both wild-type and NNRTI-resistant HIV-1. It is hoped that TMC125 will be part of the next generation of antiretrovirals with activity against resistant virus and a high genetic barrier to the development of resistance, which will help address a major unmet clinical need.

The DUET-1 and DUET-2 randomised, phase III studies examine the efficacy, safety, and tolerability of TMC125 compared with placebo in treatment-experienced patients with NNRTI-resistant HIV-1 infection. After 24 weeks, a higher proportion of patients who received TMC125 achieved a viral load of less than 50 copies per mL than did those in the placebo group (56% vs 39% in DUET-1 and 62% vs 44% in DUET-2). Furthermore, the safety and tolerability profile of TMC125 was generally comparable with placebo.

The authors of DUET-2, Adriano Lazzarin (San Raffaele University, Milan, Italy) and colleagues point out that: "The magnitude of the results seen with TMC125 and the similarity of the responses across both trials done in different countries, indicate the higher genetic barrier to resistance of TMC125 compared with currently available NNRTIs and its activity against NNRTI resistant virus are central to the ability of TMC125 to produce significantly better virological responses than the placebo group in treatment experienced patients. The maintenance of the response to 24 weeks without additionally clinically relevant tolerability concerns further suggests that TMC125 is an encouraging new agent in this antiretroviral class."

In an accompanying Comment, Bernard Hirschel and Thomas Perneger (Geneva Hospital, Geneva, Switzerland) argue that important questions have been left unanswered, including: "Quality-of-life measurements, and detailed correlations between resistant genotype and treatment success which may help gauge etravirine's prospects in individual patients."