TDM in clinical practice

Some of the most forthright commentary on using TDM in clinical practice was provided by Dr Ceppie Merry, who began with a quotation from J. Schentag that ‘if we continue in the practice of ‘one dose for all’ we will quickly enter unmanaged chaos and total irrationality’.

Dr Merry previously worked closely with David Back lab in Liverpool to provide TDM for all patients attending St James Hospital in Dublin. For the last ten months Dr Merry has been involved in clinical practice in Chicago. As more patients see their second and third-line therapies fail, and only a limited number of really new drugs look likely to reach the market in the next couple of years ‘it is far from certain that the pharmaceutical industry alone can help us out of this situation. Maybe we have to make better use out of what we have now, especially for those patients who have run out of other options.’

Dr Merry highlighted the differences between scientific approaches to the introduction of resistance testing and that of TDM, as ‘one of the double standards in HIV therapy today’. While debate will no doubt continue to refine the therapeutic ranges for individual drugs and the most useful sampling points, it is now at least generally recognised that there is a relationship between drug concentrations and outcome, and that the critical factor is time above minimum inhibitory concentration (MIC).

Caveats against use of TDM given in the recent JAMA guidelines for treatment of HIV include cost, quality assurance and uncertainty about optimal use – but these are all factors that remain to be proven for resistance assays, although theses are now routinely provided in the US. In practice, integrating TDM 2-3 weeks into a new regimen offers the potential not only to ensure adequate drug potency when its is most needed, but by increasing the duration of that regimen, will reduce the need for more costly resistance tests upon treatment failure.

Dr Merry concluded by suggesting that the experience of doctors and researchers interested in this area who were present at the meeting, many of whom had been involved in using TDM for PIs for over five years, may be best focused as an expert advisory panel. This would be an important practical outcome from this symposium and we hope it is one that is taken up by the organisers of the meeting. [1]