Therapeutic Drug Monitoring for Antiretroviral Therapy: Usefulness and Limitations

The role of therapeutic drug monitoring (TDM) in the management of antiretroviral drugs is a topic of increasing interest. If TDM is to be incorporated into patient care, it is essential that randomized controlled trials demonstrate that this intervention is both of clinical benefit for the patient and cost-effective. Such trials are in progress. Even without these data it makes intuitive sense to at least ensure drug concentration is maintained above certain levels to get optimal antiviral effect. Since nucleoside reverse transcriptase inhibitors (NRTIs) have to be intracellularly phosphorilated and the correlation between plasma nucleosides and intracellular triphosphates is poor, most attention has focused on the protease inhibitors (PIs). Arguments in favour of TDM for PIs include: Low drug exposure correlates with poor virological response, marked inter-individual variability in drug concentrations, complex drug interactions, and high plasma levels correlating with toxicity. However, it is unclear which PK values (Cmax, Cmin, AUC) are the most important to determine, although preliminary data support the use of single trough levels as a good parameter for this purpose. For non-nucleoside reverse transcriptase inhibitors (NNRTIs), blood drug levels are almost always more than 10- to 100-fold above the IC 50 when used at the recommended doses. However, recent clinical trials have underlined that critical blood levels, which are 1-2 logs above the in vitro IC 50 , need to be reached if long-term viral suppression is to be achieved. If this is the case, TDM might also be useful when using NNRTIs.