Background: Adequate plasma concentrations of antiretroviral drugs (ARV) are key for the achievement and maintenance of viral suppression in HIV-infected patients. Multiple factors may lead to elevated or subtherapeutic drug levels, causing toxicity or treatment failure, respectively. Therapeutic drug monitoring (TDM) might help to detect and correct such abnormalities early into treatment.

Methods: We retrospectively analysed all the requests for TDM of protease inhibitors (PI) and nonnucleoside reverse transcriptase inhibitors (NNRTI) from patients attending our HIV clinic during the last 2 years. Since then, TDM has become part of the routine available tests at out institution. Blood had been drawn before the morning dose in all instances, and estimations of trough levels were made accordingly. Drug concentrations were measured by a validated HPLC-UV method. ARV agents requested for TDM and the chosen therapeutic concentrations were: APV (1.25 mg/mL), IDV (0.15 mg/mL), LPV (5 mg/mL), NFV (0.8 mg/mL), SQV (0.1mg/mL), EFV (1-4 mg/mL) and NVP (3.4-6 mg/mL).

Results:  We examined 169 requests from 143 different HIV-infected patients. The reasons for requesting TDM were: suspected drug toxicity (59%), unexpected virological failure (39%) and possible drug interactions (2%). For each ARV agent the number of requests was: EFV (41%), NVP (32%), LPV (17%), APV (6%), SQV (3%), IDV (0.5%) and NFV (0.5%). High drug levels were confirmed in 37% of patients with suspected drug toxicity (LPV=1, EFV=16 and NVP=20). Low drug levels were recognized in 42% of patients failing therapy (APV=2, LPV=14, EFV=7 and NVP=5). Based on the results of TDM, dosage modifications were made in 32% of patients having drug levels out of the therapeutic range: dose reductions 10, dose increases 8, and changes of regimen 2. These therapeutic interventions achieved their clinical goal (reducing toxicity or improving viral suppression) in 80% of patients (16/20), and adequate plasma concentrations were confirmed in all cases (11/11) in which drug levels were again analyzed.

Conclusions:  TDM is a useful tool in the management of ARV therapy when PI and/or NNRTI are prescribed. Early recognition of toxic levels of NNRTI and subtherapeutic concentrations of PI are the most frequent findings. Drug adjustments following TDM seem to be of benefit in most instances.

Keywords: Therapeutic Drug Monitoring