Neuman Manuela G, Malkiewicz Izabella M, Phillips Elizabeth J, Rachlis Anita R, Ong Debra, Yeung Elaine, Shear Neil H
Department of Pharmacology, University of Toronto, Canada.
Ther Drug Monit. 2002 Dec;24(6):728-36. doi: 10.1097/00007691-200212000-00008.
Patients infected with the human immunodeficiency virus (HIV) are at higher risk for adverse drug reactions from trimethoprim-sulfamethoxazole (TMP-SMX) than the HIV-negative population. Studying the HIV-positive population the authors aimed to validate the predictive and diagnostic value of the lymphocyte toxicity assay (LTA) for adverse drug reactions. Patient lymphocytes were analyzed for toxicity to SMX and TMP. Of 35 enrolled HIV patients, 18 had TMP-SMX hypersensitivity syndrome reaction (HSR); 10 tolerated the drug; and 5 had never received the drug. When cases with HSR were compared with controls that tolerated the drugs, cytotoxicity was higher for cases: 29.5% +/- 10.1% versus 19.3% +/- 11.2% for SMX (P < 0.022) and 25.0% +/- 11.9% versus 16.3% +/- 11.0% for TMP (P < 0.04). The authors' proposed threshold value for assigning positive results for TMP and SMX hypersensitivities was 22.5%. The LTA has a strong potential for use as a diagnostic tool to assess TMP-SMX hypersensitivity in HIV-infected individuals. Larger patient populations, as well as in vitro studies are needed to further address the reasons for elevated results in immunocompromised patients and to validate the usefulness of the test.
感染人类免疫缺陷病毒(HIV)的患者比未感染HIV的人群发生甲氧苄啶-磺胺甲恶唑(TMP-SMX)药物不良反应的风险更高。作者通过对HIV阳性人群的研究,旨在验证淋巴细胞毒性试验(LTA)对药物不良反应的预测和诊断价值。分析患者淋巴细胞对SMX和TMP的毒性。在35名入组的HIV患者中,18人发生了TMP-SMX超敏反应综合征(HSR);10人耐受该药物;5人从未接受过该药物治疗。将发生HSR的患者与耐受该药物的对照组进行比较,发现病例组的细胞毒性更高:SMX的细胞毒性分别为29.5%±10.1%和19.3%±11.2%(P<0.022),TMP的细胞毒性分别为25.0%±11.9%和16.3%±11.0%(P<0.04)。作者提议将TMP和SMX超敏反应阳性结果的阈值设定为22.5%。LTA有很大潜力用作评估HIV感染个体中TMP-SMX超敏反应的诊断工具。需要更大的患者群体以及体外研究,以进一步探讨免疫受损患者检测结果升高的原因,并验证该检测方法的实用性。