NEW YORK (Reuters Health) – TMC125 (etravirine), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is a safe, effective, and well-tolerated treatment for HIV-infected patients with resistance to other NNRTIs, according to two reports in the July 7th issue of The Lancet.
"Occasionally one hears that the days of innovation in HIV therapy are over and that there is neither the scientific nor economic incentive for further progress," Dr. Bernard Hirschel and Dr. Thomas Perneger, from Geneva University Hospital in Switzerland, note in a related editorial. However, the results of the present trials and other recent studies "show that such pessimism is not justified. Not only are the new drugs effective, but they are also well tolerated."
The present reports describe the outcomes of two randomized phase III trials: DUET 1 and 2. The goal of each was to assess the efficacy, safety, and tolerability of TMC125 in treatment-experienced patients with evidence of NNRTI resistance. DUET 1 was conducted in Argentina, Brazil, Chile, France, Mexico, Panama, Puerto Rico, Thailand, and the USA, while DUET 2 took place in Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Poland, Portugal, Spain, UK, and USA.
The DUET-1 research team, led by Dr. Jose Valdez Madruga, from Centro de Referencia e Treinamento DST/AIDS in Sao Paulo, Brazil, assessed the outcomes of 612 patients who were treated with TMC125 200 mg or placebo twice daily for 24 weeks in addition to duranavir/ritonavir and an investigator-selected NRTI. Eligibility criteria included virologic failure on stable antiretroviral therapy, genotypic NNRTI resistance, viral load >5000 copies/mL, and three or more primary protease inhibitor mutations.
Discontinuation rates at 24 weeks were 14% in the TMC125 group and 18% in controls. Virologic failure was the most common reason for discontinuation.
At 24 weeks, the percentage of patients achieving a viral load of <50 copies per mL was 56% in the TMC125 group, significantly higher than the 39% seen in the placebo group (p = 0.005).
Side effects with TMC125 were generally mild or moderate in severity and were comparable to what was seen with placebo. The exceptions were rash and diarrhea, which occurred more and less frequently, respectively, with TMC125 than with placebo.
DUET-2, which included 591 patients, used the same eligibility criteria, protocol, and outcomes as DUET-1. As in DUET-1, virologic failure was the main reason for drug discontinuation. The discontinuation rates were 17% and 25% in the TMC125 and placebo groups, respectively.
Sixty-two percent of TMC125-treated patients achieved viral loads of <50 copies per mL compared with 44% of those given placebo (p = 0.0003), lead author Dr. Adriano Lazzarin, from San Raffaele University in Milan, Italy, and colleagues note.
Once again, the side effect profile and tolerability of TMC125 was generally comparable to that seen with placebo.
"The magnitude of the results seen with TMC125 in DUET-1 and DUET-2, and the similarity of the responses across both trials done in different countries, indicate that 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, given as part of an antiretroviral regimen, to produce significantly better virologic responses than the placebo group in treatment-experienced patients," Dr. Lazzarin’s team concludes.
