Therapeutic Drug Monitoring (TDM) is one of the newer diagnostic tools which is receiving a growing interest in the HIV field. The concept of TDM is based on the idea that both virological efficacy and toxicity have been shown to be related to plasma concentrations of antiretroviral agents. By monitoring these plasma concentrations, virological response may be improved and toxicity may be prevented or better manageable. TDM can only be introduced when the following criteria are met: (1) there is an accurate and precise assay available (2) relationships between plasma drug levels and effect are determined (3) effective interventions based on the TDM results are
evaluated (4) physicians have learnt to respond to TDM advices (5) a randomized controlled clinical trial has shown that patients with TDM do better than patients without TDM Many laboratories are now introducing TDM. It is important to recognize that external quality control is essential before TDM is used in patient care. For the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors relationships between plasma levels and effect have been demonstrated. Target concentrations can be defined, but it is important to realize that in treatment-experienced patients also the sensitivity of the virus to the drug should be determined. There is a wide range of possible interventions (dose modifications, addition of low-dose
ritonavir, etc.) to improve the pharmacokinetics, but few studies have evaluated these strategies. Measuring drug levels is meaningless if physicians do not follow the advices, so the introduction of TDM should be accompanied by educational programs. Finally, two randomized controlled trials have been presented recently. The French Pharmadapt study included treatment-experienced patients and could not demonstrate any benefit of TDM. The Dutch Athena study has shown that TDM of nelfinavir and indinavir in treatment-naïve patients improves the outcome after one year of follow-up. A couple of other TDM studies are now ongoing and will show us how to use TDM in clinical practice.
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