First report of ABT-378/r use in children

The first paediatric data for ABT 378/r (lopinavir/ritonavir) was presented at this meeting.

Using the liquid formulation of this new agent in a group of 100 children (comprising of 44 treatment naive and 56 experienced, but NNRTI-naive), the results look as promising as has been seen in recent adult trials. This will offer patients and clinicians an important new option in an area with more limited choice of antiretrovirals than that of adult subjects.

Study M98-940 is a phase I/II of co-formulated ABT 378/r, now branded Kaletra, at two doses in combination with NRTIs (and nevirapine in experienced subjects), in treatment naive and treatment experienced paediatric patients. The mean average age of the children was 4.8 years (range 6 months to 10.2 years) for the naive children and 5.7 years (range 8 months to 12.6 years) for the experienced group. Subjects were defined as naive if they had received <3 months prior ARV therapy (or <1 week treatment with 3TC).

Both groups of children were randomised to receive twice daily doses of either 230/57.5mg per metre squared or 300/75mg per metre squared of ABT 378/r. In addition the naive children received d4T and 3TC and the experienced ones received nevirapine and one or two open label NRTIs. All subjects were switched to the higher dose following an analysis of safety, tolerability and efficacy and week 3 pharmacokinetics.

At 24 weeks 82% of nave and 66% of experienced children were undetectable (below <400 copies) by intent-to-treat analysis and their CD4 counts had risen by 328 and 335 respectively. Of the 100 children enrolled in the study there was only 1 discontinuation as of week 24, this was due to Burkitts lymphoma and problems with its treatment and not related to study drug. There were very few adverse events of probable relationship to study drug. Overall the presenting investigator Dr Violari described the results as ‘very impressive indeed.’

Questions raised by the audience included the all-important one for paediatrics, ‘But what does it taste like?’ and the answer came back, ‘It’s not great, but the children got used to it, and it didn’t cause anyone to stop their treatment’.