Therapeutic drug monitoring of antiretroviral agents

Abstract

HIV+ patients fail antiretroviral therapy due to inadequate drug concentrations reaching the site of viral replication and/or the development of viral resistance to the antiretroviral agents. Adequate drug concentrations may not be reaching the virus due to poor compliance, poor absorption, or other pharmacokinetic factors such as metabolism, elimination, and drug interactions. The most important and most common pharmacokinetic drug interactions involve inhibition of metabolism, induction of metabolism, altered drug absorption, inhibition of renal excretion, and displacement from plasma protein binding sites. If a patient is failing antiretroviral therapy, TDM of antiretroviral agents could help in determining both adequacy of drug concentrations and patients' adherence. Ongoing studies will determine whether total drug concentration or free drug concentration of the protease inhibitors is the best predictor of response. Trough concentrations could prove to be the most important predictor of response, but additional studies are needed to compare trough, peak, and AUC concentrations with response to treatment. Finally, if some patients fail therapy due to inadequate drug concentrations, then increasing the dose could benefit patients' outcome and increase longevity. Clinical trials are needed that compare patients who receive a fixed-dosage regimen with patients who have adjusted dose regimens. Such a study is the best way to determine the true value of TDM of the antiretrovirals.