van Luin Matthijs, Bannister Wendy P, Mocroft Amanda, Reiss Peter, Di Perri Giovanni, Peytavin Gilles, Molto José, Karlson Anders, Castagna Antonella, Beniowski Marek, Lundgren Jens D, Burger David M
Department of Clinical Pharmacy, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Antivir Ther. 2009;14(1):75-83.
Co1nflicting data exist regarding the effect of efavirenz (EFV) plasma concentrations on central nervous system (CNS) toxicity. We aimed to determine whether patients with high EFV plasma concentrations have an increased likelihood of toxicity-driven EFV discontinuations.
EFV plasma concentrations were measured from patients in the EuroSIDA study starting EFV after 1 January 1999. Patients with a plasma concentration available were divided into those that discontinued EFV because of any toxicity or by the choice of the patient or physician within 2 years (TOXPC group) and those that continued EFV for > or = 2 years (no toxicity group). Multivariable logistic regression modelling was used to investigate the effects of the EFV plasma concentration and those of other potentially relevant factors on the risk of toxicity-induced EFV discontinuations.
A total of 843 patients were included. Of these patients, 138 patients (16.4%) discontinued EFV because of TOXPC and 705 (83.6%) patients continued EFV for 22 years. A total of 20 (14.5%) patients in the TOXPC group had high EFV plasma concentrations (>4.0 mg/l) compared with 99 (14.0%) patients in the no toxicity group (P = 0.890). A positive hepatitis C status (P = 0.026), but not the EFV plasma concentration, was an independent predictor of toxicity-driven EFV discontinuations.
No association was found between EFV plasma concentrations and the risk of EFV discontinuations because of (CNS) toxicity. This result questions the designation of EFV plasma concentrations >4.0 mg/l as being 'toxic', at least when defined by treatment discontinuation.
关于依非韦伦（EFV）血浆浓度对中枢神经系统（CNS）毒性的影响，存在相互矛盾的数据。我们旨在确定血浆EFV浓度高的患者因毒性而停用EFV的可能性是否增加。
对1999年1月1日后开始使用EFV的欧洲艾滋病临床数据库（EuroSIDA）研究中的患者测量其血浆EFV浓度。有可用血浆浓度的患者被分为在2年内因任何毒性或由患者或医生选择而停用EFV的患者（毒性停药组）和继续使用EFV≥2年的患者（无毒性组）。使用多变量逻辑回归模型研究EFV血浆浓度及其他潜在相关因素对毒性诱导的EFV停药风险的影响。
共纳入843例患者。其中，138例患者（16.4%）因毒性停药组原因停用EFV，705例（83.6%）患者继续使用EFV达2年。毒性停药组共有20例（14.5%）患者血浆EFV浓度高（>4.0mg/l），而无毒性组有99例（14.0%）患者（P = 0.890）。丙型肝炎病毒感染状态为阳性（P = 0.026），而非EFV血浆浓度，是毒性驱动的EFV停药的独立预测因素。
未发现EFV血浆浓度与因（CNS）毒性而停用EFV的风险之间存在关联。这一结果对将EFV血浆浓度>4.0mg/l定义为“有毒”提出了质疑，至少当以治疗中断来定义时是如此。
