Improving HIV infection management using antiretroviral plasma drug levels monitoring: A clinician's point of view

Due to genetic and environmental factors, there are wide inter-patient differences when measuring drug exposure to a standard dose. If there is a relationship between drug exposure and efficacy or toxicity, this inter-patient variability carries various risks to develop toxicity or failure. Therapeutic drug monitoring is an attempt to adjust the dose to obtain a level within a therapeutic range consisting in a minimum plasma concentration needed to be efficacious and a maximum plasma concentration not to exceed to avoid toxicity. Many studies have shown a relationship between various pharmacokinetic parameters and drug toxicity or efficacy for HIV protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Therapeutic drug monitoring (TDM) proves to be a useful tool to assess adherence, to investigate drug-drug interactions between antiretroviral (ARV) drugs or with co-medications, to prevent some ARV drug toxicities, to adjust the dosage in particular populations, and to increase ARV efficacy of some drugs in naive patients. The integration of virological and pharmacological parameters, using inhibitory quotients, looks promising to improve therapy in ARV-experienced patients. Effective and non-toxic target concentrations will be determined for all present and future antiretroviral drugs covering the extended spectrum of naive patients to multiple failures. In this article, we review the rationale of TDM for antiretroviral drugs, the retrospective and prospective studies assessing plasma drug concentrations in relation with antiretroviral toxicity or efficacy, and the actually recommended or proposed indications for TDM. We also highlight the benefits and limits of this tool as an adjunct in the care of HIV-infected patients.