The Family Clinic, Imperial College Healthcare NHS Trust, St Mary's Hospital, Praed Street, London, UK.
Department of Paediatric Infectious Diseases and Immunology, Great North Children's Hospital, Newcastle-upon-Tyne, UK.
Clin Drug Investig. 2018 Mar;38(3):231-238. doi: 10.1007/s40261-017-0605-1.
Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI) is used globally as first-line antiretroviral therapy (ART) in combination with a dual nucleoside backbone in adults and children from 3 years of age. Up to 40% of adults taking efavirenz report central nervous system (CNS) adverse effects, and the rates of discontinuation of efavirenz-based treatment are higher than other first-line regimens. Data on efavirenz discontinuation are more limited for children and adolescents.
In this study, we aimed to describe our single-centre paediatric experience of efavirenz.
Retrospective case-note audit of children and adolescents with perinatally acquired HIV who ever received efavirenz.
From 1998 and 2014, 51 children and adolescents aged ≤ 18 years received efavirenz-based treatment. Median age at efavirenz initiation was 9.4 years (interquartile range [IQR] 7-13). More than half (30/51; 59%) subsequently switched off efavirenz-15 (29%) following virological failure with NNRTI-associated resistance mutations, and 16 (30%) after reporting adverse effects. Of those who experienced adverse effects, one-fifth (19.6%) described CNS adverse effects, including sleep disturbance, reduced concentration, headaches, mood change and psychosis. Four children (three males) developed gynaecomastia, two developed hypercholesterolaemia, and one child developed Stevens-Johnson syndrome. Comparison between those reporting side effects and the rest of the cohort showed no difference in age, sex, initial CD4 cell count, viral suppression, length of efavirenz-based treatment, weight, or efavirenz dose per kilogram. Median time to switch was 25 months (IQR 10-71) in those who experienced side effects and 22 months (IQR 12-50) for virological failure. One individual experienced both virological failure and adverse effects.
Almost two-thirds of this paediatric cohort switched from efavirenz-based treatment to an alternative regimen, due in equal proportions to both virological failure and toxicity. The majority of side effects involved the CNS. First-line regimens with improved tolerability and a higher genetic barrier to resistance should be the preferred option for children.
依非韦伦是一种非核苷类逆转录酶抑制剂（NNRTI），在全球范围内被用作成人和 3 岁及以上儿童的一线抗逆转录病毒治疗（ART），与双核苷骨干药物联合使用。多达 40%的服用依非韦伦的成年人报告中枢神经系统（CNS）不良反应，且依非韦伦为基础的治疗停药率高于其他一线方案。关于儿童和青少年的依非韦伦停药数据则更为有限。
本研究旨在描述我们单中心儿科使用依非韦伦的经验。
对曾接受过依非韦伦治疗的围生期感染 HIV 的儿童和青少年进行回顾性病历审计。
1998 年至 2014 年，51 名年龄≤18 岁的儿童和青少年接受了依非韦伦为基础的治疗。依非韦伦起始中位年龄为 9.4 岁（四分位间距 [IQR] 7-13）。超过一半（30/51；59%）的患者因发生 NNRTI 相关耐药突变的病毒学失败而停用依非韦伦-15（29%），16 名（30%）因报告不良反应而停药。在出现不良反应的患者中，五分之一（19.6%）描述了 CNS 不良反应，包括睡眠障碍、注意力不集中、头痛、情绪变化和精神病。4 名儿童（3 名男性）出现了男性乳房发育症，2 名出现了高胆固醇血症，1 名出现了 Stevens-Johnson 综合征。在报告不良反应的患者与其他患者之间的比较中，年龄、性别、初始 CD4 细胞计数、病毒抑制、依非韦伦治疗时间、体重或依非韦伦剂量与体重的比例均无差异。出现不良反应的患者中位换药时间为 25 个月（IQR 10-71），病毒学失败的患者为 22 个月（IQR 12-50）。有 1 名患者同时发生了病毒学失败和不良反应。
在这项儿科队列中，近三分之二的患者因病毒学失败和毒性而改用替代方案，其中病毒学失败和毒性的比例相当。大多数不良反应涉及 CNS。具有更好耐受性和更高耐药遗传屏障的一线方案应作为儿童的首选。
