Si chiama TMC 278 un nuovo non nucleosidico della Tibotec in sviluppo. Di seconda generazione, ora passa alla fase IIb. Promettenti i risultati degli studi preliminari.Descrizione dello studio:
Dr. Goebel and colleagues in Russia and Britain randomized 47 treatment-naive individuals to placebo or 25 mg, 50 mg, 100 mg, or 150 mg TMC278 given once daily for 7 days as an oral solution. Study participants began treatment with a median viral load of 4.5 log10 copies/mL (range 3.5-5.9 log10 copies/mL) and a median CD4+ cell count of 292 cells/mm3 (range, 29-590 cells/ mm3).
After 7 days, the median HIV-1 load dropped 1.29 logs with TMC278 25 mg, 1.23 logs with 50 mg, 1.07 logs with 100 mg, and 1.17 logs with 150 mg , there was no change with placebo (P value vs placebo < .01 for all treatment groups). The apparent virologic equivalence between arms prompted speculation at the conference that an even lower dose may be possible. However, Dr. Goebel noted that longer treatment may distinguish between the doses.
Although enrollees could have no antiretroviral experience, 2 did have resistance-related mutations when the study began: the lamivudine-related M184V mutation plus the K103N NNRTI mutation in 1 person; in the other, the NNRTI mutations K103N and Y181C plus the protease inhibitor mutation L90M. The first person had a 0.53-log fall in viral load with TMC278 and the second a 0.73-log drop.
No one stopped treatment because of toxicity in this brief study, and no serious side effects were reported. The median CD4+ cell count climbed 55 cells/mm3 in 7 days.
A multinational phase 2b dose-finding study begins in March 2005.
1. Goebel F, Yakovlev A, Pozniak A, et al. TMC278: potent anti-HIV activity in antiretroviral therapy-naive patients. Program and abstracts of the 12th Conference on Retroviruses and Opportunistic Infections; February 22-25, 2005; Boston, Massachusetts. Abstract 160.
2. de Bethune MP, Andries K, Azijn H, et al. TMC278, a new potent NNRTI with an increased barrier to resistance and good pharmacokinetic profile. Program and abstracts of the 12th Conference on Retroviruses and Opportunistic Infections; February 22-25, 2005; Boston, Massachusetts. Abstract 556.