Pharmacy Service, University Hospital Infanta Sofía, San Sebastián de Los Reyes, Paseo de Europa 34, 28709, Madrid, Spain.
Pharmacy Department, Pharmacy Faculty, University of Concepcion, Víctor Lamas 1290, 4070386, Concepción, Chile.
Clin Drug Investig. 2019 Nov;39(11):1125-1131. doi: 10.1007/s40261-019-00829-x.
Antiretroviral therapy has changed the history of HIV infection from a lethal disease to a chronic infection, with the emergence of long-term adverse effects. Herein we present a case of a heavily treated HIV-infected man in whom antiretroviral toxicity had been observed. The lopinavir/ritonavir plasma concentrations at standard doses were significantly above the recommended levels. Pharmacogenetic analysis revealed a polymorphism in the DRD3 gene associated with a decrease in the rate of drug metabolism. Additionally, the patient's low body mass index could have contributed to a greater degree of patient exposure to the drug. After the withdrawal of tenofovir disoproxil and the establishment of individualized protease inhibitor monotherapy at reduced doses, a decrease in the intensity of adverse events was observed, while the clinical outcomes were maintained. The pharmacokinetic-pharmacogenetic analysis was shown to be a tool of huge interest for the management and durability of antiretroviral therapy.
抗逆转录病毒疗法改变了 HIV 感染的历史，使它从一种致命的疾病转变为一种慢性感染，同时也出现了长期的不良反应。在此，我们报告了一例经大量治疗的 HIV 感染男性患者，该患者出现了抗逆转录病毒毒性。标准剂量的洛匹那韦/利托那韦血浆浓度明显高于推荐水平。药物遗传学分析显示，DRD3 基因的一种多态性与药物代谢率降低有关。此外，患者的低体重指数可能导致其对药物的暴露程度更大。在停用替诺福韦酯和建立个体化蛋白酶抑制剂单药治疗且降低剂量后，观察到不良反应的强度降低，而临床结果得到维持。药代动力学-药物遗传学分析被证明是管理和维持抗逆转录病毒治疗的一个非常有意义的工具。
