Highlights from the First International Workshop on Clinical Pharmacology of HIV Therapy, Noordwijk, The Netherlands, March 30-31, 2000.
Therapeutic drug monitoring, although recommended in French and (implicitly) in UK treatment guidelines, is still an inexact science. Nijmegen University Medical Centre in the Netherlands organised the first international comparison study to determine how much variation exists in drug level measurements from different laboratories.
The researchers sent plasma samples from HIV-negative volunteers, spiked with three different, standardised doses of indinavir, nelfinavir, ritonavir and saquinavir, to 10 laboratories worldwide. Measurements were considered to be correct if they fell within 20% of the concentration of drug that should have been present based on the original weight of drug dissolved in the plasma sample. This method had been chosen to minimise interpersonal variation in drug metabolism.
Indinavir was the drug with the most consistent detection rate; 86% of measurements were correct. In contrast, ritonavir was poorly measured; only 42% of measurements were correct. For saquinavir and nelfinavir, two-thirds (65%,67%) of measurements were correct.
Only one laboratory got all the measurements correct, and in all cases the ability to detect low concentrations correctly was worse than for other concentrations.
A French national study also found significant variations between 27 laboratories.
However, Professor David Back pointed out that the results represented a considerable improvement on past quality control findings.
"It's probably surprising how close these results were to each other", he told aidsmap. "They found an average variance of 50% between labs, whereas a study by Agouron last year of nelfinavir drug level monitoring from five US labs found a five-fold variation between labs. Now that we have a quality control system established in Europe I would expect to see continuous improvement."
References
Aarnoutse R et al. International Interlaboratory quality control (QC) program for therapeutic drug monitoring (TDM) in HIV infection: first results. First International Workshop on Clinical Pharmacology of HIV therapy, Noordwijk, abstract 1.4, 2000.
Palette C et al. Evaluation of serum anti-HIV drugs determinations in France: preliminary results of a national quality control surveyFirst International Workshop on Clinical Pharmacology of HIV therapy, Noordwijk, abstract 1.5, 2000.