Background: Therapeutic drug monitoring (TDM) of antiretroviral drugs (ARVs) is used to improve the efficacy and safety of ARVs, but there is little interest for the systematic or random TDM of ARVs in the medical management of patients with acquired immune deficiency syndrome. This study aimed to evaluate a different approach and test the potential advantages of TDM as part of medical treatments when clinical problems are identified in human immunodeficiency virus-infected patients.
Methods: The authors conducted a prospective, noncontrolled, cohort study on 544 human immunodeficiency virus-positive patients treated either with a protease inhibitor (PI), atazanavir/lopinavir, or with a nonnucleoside reverse transcriptase inhibitor (NNRTI), efavirenz/nevirapine. Patients who had virological failure, clinical signs of toxicity, or a risk of pharmacokinetic interactions were identified as having medication-related problems (MRPs), and they were scheduled for TDM of the PIs or NNRTIs. Cases with drug levels outside the range were subjected to intervention, and a second determination of plasma levels and viral load was scheduled to assess their response to the intervention.
Results: Of the 521 treatment courses analyzed, 173 (32.4%) presented at least 1 MRP during the study. The TDM yielded abnormal results in 52.5% of the 198 identified MRP cases (95% CI: 45%-59%). The patients treated with PIs had an increased risk for having drug plasma levels that fell outside the normal range compared to those treated with NNRTIs (relative risk =1.36, 95% CI: 1.04-1.79). The TDM-guided interventions contributed to the resolution of 52.1% of the cases that involved treatment courses with MRPs and abnormal drug plasma levels.
Conclusions: MRPs, including therapeutic failure, were common in the patients who were included in the study. A high proportion of the treatment courses involving such MRPs also presented abnormal plasma drug levels. The TDM-guided interventions are advantageous under these situations because they allow the continuation of treatments that would otherwise be substituted by more complex and costly alternatives.