The role of therapeutic drug monitoring in the management of patients with human immunodeficiency virus infection.

Therapeutic drug monitoring (TDM) is a well-established method to optimize dosing regimens in individual patients for drugs that are characterized by a narrow therapeutic range and large interindividual pharmacokinetic variability. For some antiretroviral drugs, mainly nonnucleoside reverse transcriptase inhibitors and protease inhibitors, TDM has been proposed as a means to improve the response in human immunodeficiency virus-infected patients. In contrast, nucleoside reverse transcriptase inhibitors do not show a predictable plasma concentration-response (toxicity, efficacy) relationship, and intracellular analyses are expensive. Therefore, TDM is generally not recommended for this class of drugs. TDM has been successfully applied in the clinical practice for certain antiretroviral drugs, but there are ongoing research efforts on the use and refinement of TDM for human immunodeficiency virus treatment, and convincing data from randomized trials are still needed. The best pharmacokinetic measures of drug exposure such as trough and peak concentrations or concentration ratios have not been unambiguously established.