Modelling-based prediction of clinical benefits from etravirine in the TMC125-C223 trial

To predict the decrease in progression to AIDS or death based on the treatment benefit of etravirine over active control on CD4 counts and HIV RNA.

In the TMC125-C223 trial, treatment-experienced patients (n = 199, baseline median CD4 99 cells/microL, HIV RNA 4.7 log10 copies/mL) received optimized background treatment plus either etravirine 400 mg bid, etravirine 800 mg bid, or control. CD4 and HIV RNA data were used to predict progression to AIDS or death with two methods: regression method - data from clinical endpoint trials were used to correlate previous CD4 and HIV RNA treatment benefits with clinical progression; CD4 categorization method - data from the EuroSIDA cohort were used to predict rates of disease progression.

At week 48, CD4 counts rose by 49 cells/microL for etravirine 800 mg bid versus 10 cells/microL for control; HIV RNA fell by -1.0 and -0.14 log10 at week 48 in the two groups. The regression method predicted a 39% comparative reduction in progression to AIDS/death from HIV RNA levels and a 33% reduction in progression from CD4 counts. The categorization method predicted a comparative reduction of 39% based on HIV RNA levels and a reduction of 31% based on CD4 counts.

Based on the efficacy results from the TMC125-C223 trial, the benefits of etravirine 800 mg bid versus control in raising CD4 counts and suppressing HIV RNA are predicted to lower progression rates to AIDS/death by 31%-39% for etravirine treatment, using two independent methods.