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Labs Inaccurate in 18% of Darunavir, Etravirine, or Raltegravir Measures
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14th International Workshop on Clinical Pharmacology of HIV Therapy, April 22-24, 2013, Amsterdam
Mark Mascolini
Antiretroviral drug monitoring laboratories incorrectly measured concentrations of darunavir, etravirine, or raltegravir in 17.9% of test samples, according to a 2011-2012 report by the International Interlaboratory Quality Control Program for Measurement of Antiretroviral Drugs in Plasma [1]. But accuracy improved from 2011 to 2012 in assessing concentrations of these newer antiretrovirals.
Researchers established the International Interlaboratory Quality Control Program in 1999 to offer drug-monitoring labs an opportunity to test and improve their performance [2]. This analysis focused on performance of participating labs in measuring levels of darunavir, etravirine, and raltegravir in 2011 and 2012.
Every year each participating lab receives two blind samples of human plasma containing low (below 1.0 mg/L), medium (1.0 to 5.0 mg/L), or high (above 5.0 mg/L) concentrations of test drugs. Low concentrations never lay below 50% of the minimum effective concentration for the test drug. Participating labs must report results within 6 weeks, and those results are stored anonymously in the Quality Control Program database. A result more than 20% different from the actual concentration is considered inaccurate.
Forty-four labs participated in the darunavir analysis, 28 in the etravirine analysis, and 30 in the raltegravir analysis. Of the 357 plasma samples tested, results were inaccurate for 64 (17.9%). Twenty-seven reported results (7.6%) were inaccurately low, and 37 (10.4%) were inaccurately high. The overall 17.9% inaccuracy rate compares with an 11.6% rate for older antiretrovirals evaluated in previous years.
In 2011 the inaccuracy rate was 21.3% for darunavir, 31.0% for etravirine, and 26.3% for raltegravir. In 2012 inaccuracy rates improved to 8.1% for darunavir, 23.2% for etravirine, and 8.3% for raltegravir, a significant difference (P = 0.002).
With darunavir as the reference for comparison, lab accuracy was significantly lower for etravirine (odds ratio 0.462, 95% confidence interval 0.246 to 0.866, P = 0.016). Performance in determining raltegravir concentrations did not differ significantly from performance with darunavir.
Compared with medium or high concentrations, performance was significantly worse in measuring low concentrations (28.6% inaccurate for low, 10.6% for medium, and 8.8% for high, P < 0.001). Multiple logistic regression analysis confirmed the worst performance in determining low concentrations (P < 0.001). The inadequate result rate did not differ significantly between labs that used the LC-MS(MS) method (41 of 200 inaccurate, 20.5%) and labs that used HPLC/UPLC (23 of 157 inaccurate, 14.6%) (P = 0.154).
The researchers conclude that "laboratories continue to have problems with adequately measuring low plasma concentrations of antiretroviral agents," particularly antiretrovirals with plasma concentrations typically below 1.0 mg/L, such as etravirine and raltegravir. The investigators encouraged labs to participate in external proficiency testing to alert them to suboptimal assay performance.
References
1. Burger DM, Krens S, Robijns K, et al. Poor performance of laboratories assaying newly developed antiretroviral agents: data for darunavir, etravirine and raltegravir from the KKGT Program. 14th International Workshop on Clinical Pharmacology of HIV Therapy, April 22-24, 2013, Amsterdam. Abstract P_28.
2. Burger D, Teulen M, Eerland J, Harteveld A, Aarnoutse R, Touw D. The International Interlaboratory Quality Control Program for Measurement of Antiretroviral Drugs in Plasma: a global proficiency testing program. Ther Drug Monit. 2011;33:239-243. http://www.ncbi.nlm.nih.gov/pubmed/21383652
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