Combining resistance and pharmacology for optimum patient care

Therapeutic drug monitoring is now incorporated into the treatment guidelines of many countries. In this review, we describe the use and limitations of therapeutic drug monitoring, and how added benefit might accrue from integrating therapeutic drug monitoring with resistance testing in the form of inhibitory quotients.

Although the unselected use of therapeutic drug monitoring in current (ritonavir-boosted) protease inhibitor or nonnucleoside reverse transcriptase inhibitor-containing regimens has yet to be established, therapeutic drug monitoring is likely to be useful in selected groups of patients, such as children, pregnant women, patients with malabsorption, or in specific clinical scenarios, such as liver impairment, drug interactions, suspected toxicity, assessing adherence or treatment failure. One problem with therapeutic drug monitoring is that efficacy targets relate mainly to drug-sensitive virus. Inhibitory quotients may be a better predictor of response in treatment-experienced patients.

In this review, we discuss the different derivations of inhibitory quotients. Inhibitory quotients have been shown to be predictive of virological response in heavily pretreated patients receiving lopinavir, amprenavir, saquinavir, atazanavir and tipranavir. Lack of standardization and consensus on which inhibitory quotient to use are major factors which limit their introduction into clinical practice.