Interpretation

The concentration is interpreted while taking into consideration all patient information provided including:

 

The interpretation report includes different information:

Interpretation reports will be sent by mail 2 to 3 weeks after the sample has been received at the program's laboratory. Click here for a fictitious example of an interpretation report.

Pharmacokinetic / pharmacodynamic parameters: 

Various pharmacokinetic / pharmacodynamic (PK/PD) parameters are used for the interpretation of antiretroviral plasma concentrations. Factors that influence the choice of the apppropriate parameter for a given patient are: antiretroviral analyzed, time post-dose of the sample, prior virologic failure to protease inhibitors and viral resistance.

The target values for the PK/PD parameters are detemined after an extensive review of the primary literature.

Plasma concentration (random)

Plasma concentration measured, regardless of the time post-dose.

If the sample was not taken at the end of the dosing interval, the plasma concentration will be compared to the mean pharmacokinetic population curve and the minimum target curve. Appropriate time post dose for sampling depends on the dosing interval and the antiretroviral agent measured (see Requesting TDM/Blood drawing). 

Minimum concentration

The minimum concentration (Cmin) is the lowest concentration measured in the dosing interval. Cmin is often but not always the concentration at the end of the dosing interval (trough concentration or Ctau).  If the sample has not been taken at the end of the dosing interval but in the elimination phase, it is possible to extrapolate the Ctau using the mean elimination half-life for the given antiretroviral. This, however, remains an estimate that may be inaccurate if an individual has a shorter or longer antiretroviral elimination half-life than the mean. 

For simplicity, the Cmin is used on this site to designate both the real Cmin and the trough concentration (Ctau). Cmin is the most commonly used parameter to determine if the concentration is therapeutic in patients with virus harbouring no mutations conferring resistance to the antiretroviral analyzed.

Note that the Cmin target for certain protease inhibitors (PIs) may be higher for patients with prior virologic failure to PIs compared to those without, hence the importance of providing this information on the data collection form. Also, the Cmin may only be calculated if both the date and time of the last dose and of the blood procurement are specified on the data collection form and if the sample is taken during the elimination phase (see Requesting TDM/Blood drawing). 

Maximum concentration

The maximum concentration (Cmax) is a less commonly used parameter and is not particularly helpful to predict the virologic efficacy. Cmax represents the highest concentration after the intake of a given drug and occurs generally between 1 to 4 hours post-dose. It is mostly used to evaluate if malabsorption is present.  Indinavir Cmax has also been associated with the development of adverse effects.

C-all

The C-all is a parameter used when interpreting raltegravir concentrations in patients with prior virologic failure to three classes of antiretroviral agents. C-all is the geometric mean of all concentration results taken at any point in time during the dosing interval. 

Genotypic inhibitory quotient

The genotypic inhibitory quotient (GIQ) combines viral resistance data with patient pharmacokinetic data and is used when interpreting most plasma concentrations of protease inhibitors (PIs) for patients with virus harbouring protease mutations. The GIQ allows the individualization of Cmin targets for each patient based on the viral resistance acquired. GIQ values have been shown to independently predict virologic response to PI therapy in treatment-experienced populations.

GIQ = Cmin / number of resistance conferring mutations for the antiretroviral analyzed

It is important to note that the GIQ may only be calculated if both the date and time of the last dose and of the blood procurement are specified on the data collection form, if the sample is taken during the elimination phase and if protease mutations conferring resistance to the protease inhibitor measured are documented (see  Requesting TDM/Blood drawing). 

Virtual inhibitory quotient

The virtual inhibitory quotient (vIQ) combines virtual phenotypic viral resistance data with patient pharmacokinetic data and may be used when interpreting plasma concentrations of darunavir in patients with virus with decreased sensitivity to this antiretroviral.

vIQ = Cmin / (IC50 x fold change)
IC50: concentration that inhibits viral replication by 50%, adjusted for protein-binding
Fold change: fold increase in IC50 of patient virus versus reference virus, as determined by the virtual phenotype

It is important to note that the vIQ may only be calculated if both the date and time of the last dose and of the blood procurement are specified on the data collection form, if the sample is taken during the elimination phase and if virtual phenotypic viral resistance data (fold-change) is provided (see Requesting TDM/Blood drawing).