Therapeutic drug monitoring (TDM) refers to the adjustment of drug doses based on measured plasma concentrations to attain values within a “therapeutic window.” Clinicians have used these principles for years to adjust doses of drugs including theophylline, aminoglycosides, digoxin, and anticonvulsants. However, TDM has not generally been used for monitoring the treatment of chronic infectious diseases. There is growing evidence that TDM may be useful in some circumstances to insure HIV-infected patients have adequate blood concentrations for efficacy without producing toxicity. This may be especially true for children where there is wide variability in plasma concentrations. A number of critical questions remain to be addressed before TDM is used routinely in HIV infection. To this end, several large clinical trials have recently been initiated that may help to define its role.

A number of retrospective studies have demonstrated that plasma concentrations of antiretroviral drugs correlate with antiviral activity [1–4]. It is clear that drug concentrations are an important predictor of response to HIV treatment. However, these findings are quite different than assessing the value of using TDM in the clinic to guide antiretroviral therapy for an individual. This chapter will review the available data, describe which drugs can be monitored, indicate when samples should be collected, and address practical concerns and issues for the clinician.

Drugs as TDM candidates

Some antiretrovirals share many of the characteristics of drugs that require monitoring of plasma levels, including variable inter-subject pharmacokinetics, serious consequences if there is a lack of effect or drug toxicity, documented relationships between drug concentration and effect or toxicity, identification of a therapeutic range, and the availability of rapid and accurate assays.