Trough concentrations of protease inhibitors are generally accepted to be predictive of viral response , suggesting that this parameter is a reasonable target for therapeutic drug monitoring. Although several methods for measuring plasma antiretroviral concentrations are available, none have been reviewed by Clinical Laboratory Improvement Amendments (1988)-approved proficiency testing programmes. To help assure interassay agreement, our laboratory is registered with the AIDS Clinical Trials Group Quality Assurance/Quality Control program for clinical measurement of antiretroviral agents . Finally, in the clinical setting, precisely timed samples are difficult to obtain, and the high degree of interpatient pharmacokinetic variability can limit the accuracy of patient drug exposure estimations from a single drug concentration. One solution is to use Bayesian models. This method leverages previous population pharmacokinetic information to estimate the entire individual patient pharmacokinetic profile .
Although atazanavir trough concentrations are highly variable and may not be associated with viral response , a detectable trough ensures that drug exposure is maintained throughout the dosing interval. Furthermore, until the minimum effective concentration of atazanavir is defined, it is not known whether lower atazanavir concentrations during PPI use increases the risk of viral failure. Certainly, co-administration should be avoided whenever possible. However, for those patients with viral control who are currently receiving atazanavir–ritonavir and a PPI, we recommend measuring trough atazanavir concentrations. If concentrations are detectable, ideally above the population-predicted 50th percentile for unboosted atazanavir, continued atazanavir–ritonavir and PPI use can be considered.
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