24-week efficacy of TMC114 in PI-experienced patients
Graham McKerrow, HIV i-Base
An interim 24-week analysis of data from 497 patients in a multinational study of the new protease inhibitor TMC114 with ritonavir, demonstrated exciting efficacy in three-class-experienced patients with limited treatment options and was presented as an oral late-breaker session.
Four different dosing regimens were generally safe and well tolerated and the researchers concluded by recommending a dose of 600/100mg twice a day for further clinical development in treatment experienced patients because on a series of measures that dose was as potent or more potent than others and produced comparable or fewer side effects.
TMC114 had previously shown potent activity in protease inhibitor (PI) resistant patients in a 14-day trial. The new study looked at its effect in people who had experienced at least 3 classes of antiretrovirals with prior use of at least 1 PI, had at least one primary PI mutation, and viral load >1,000 copies/mL.
Patients were randomised to receive optimal background therapy (OBR, at least 2 NRTIs with or without T-20) and one of 4 doses of TMC114/r (400/100mg once a day, 800/100mg once a day, 400/100mg BD or 600/100mg BD) or chosen PI (CPI).
Baseline median CD4 count and viral load were 141 cells/mm3 and 4.6 log10 copies/mL respectively.
Interim week 24 interim results (intent to treat) are shown in the table below. The TMC-144/r dose 600/100mg twice-daily dosing produced a greater mean change in viral load, a greater percentage of subjects with 1log or more reduction, a marginally greater percentage with fewer than 400 copies/mL, and a greater percentage with fewer that 50 copies/mL than any other group, while at the same time having the same or only a slightly higher percentage of subjects with grade 3 and 4 adverse events and a lower or comparable percentage of severe adverse events.
Mean change in CD4 was +75 cells/mm3 for TMC114/r 600/100 twice-daily vs +15 cells/mm3 for CPI. See Table 1 below.
Table 1: 24-week interim results of TMC114 vs comparitor PI
|TMC114/r||400/100 once- daily||800/100 once-daily||400/100 twice-daily||600/100 twice-daily||CPI|
|Mean HIV RNA change||-1.28||-1.43||-1.47||-1.85||-0.27|
|% > 1 log reduction||55||56||58||72||16|
|% < 400 copies/mL||46||48||58||72||16|
|% < 50 copies/mL||30||31||38||47||10|
|% grade 3 and 4 ae’s||23||26||26||26||23|
|% severe ae’s||10||17||16||9||11|
Katlama C, Berger D, Bellos N et al. Efficacy of TMC114/r in 3-class experienced patients with limited treatment options: 24-week planned interim analysis of 2 96-week multinational dose-finding trials. 12th CROI, Boston, 2005.