Clinical benefit of interventions driven by therapeutic drug monitoring

Background: Adequate plasma concentrations of antiretroviral drugs are key to achieving and maintaining long-term suppression of HIV replication. Multiple factors may influence drug levels, causing increases or reductions that may, respectively, result in toxicity or virological failure. Therapeutic drug monitoring (TDM) might help to detect and correct such abnormalities. Objective: To evaluate the usefulness of TDM in the care of HIV-infected patients in an out-patient clinical setting. Methods: All the requests for TDM of protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) for patients attending our HIV out-patient clinic from October 2000 to August 2003 were analysed. Blood samples were collected before the morning dose. Drug concentrations were measured by high performance liquid chromatography by ultraviolet waves (HPLC-UV). Results: A total of 151 requests from 137 patients were assessed. The reasons for requesting TDM were drug toxicity (59%), virological failure (39%) and possible drug interactions (2%). NNRTI levels were more often requested because of toxicity, while PI levels were more often requested because of virological failure. Elevated drug levels were confirmed in 36% of patients with suspected drug toxicity, while subtherapeutic levels were found in 37% of patients failing virologically. Based on the results of TDM, dose modifications were made in 37% of patients, allowing correction of such abnormalities in 80% of cases. Moreover, adequate plasma concentrations were confirmed in 79% of patients whose levels were assessed again. Conclusions: Therapeutic drug monitoring may be a useful tool to identify toxic levels of NNRTI and subtherapeutic concentrations of PI. Dose adjustments following TDM may ameliorate drug-related toxicities or improve virological response rates.