Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
Department of Paediatrics, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
Lancet HIV. 2019 Apr;6(4):e250-e258. doi: 10.1016/S2352-3018(18)30329-1. Epub 2019 Feb 12.
Efavirenz is commonly prescribed for children with HIV infection, yet little is known about risks of neuropsychiatric side-effects. We aimed to compare competence (social involvement, activities, and school performance) and psychopathology (internalising and externalising problems), cognitive performance (intelligence and working memory), and adherence in Tanzanian children on an efavirenz-based versus a non-efavirenz-based regimen.
In this multicentre, cross-sectional, observational study, we included consecutive children (aged 6-12 years) with HIV infection, on combination antiretroviral therapy (cART) for at least 6 months, and with viral loads of less than 1000 copies per mL from HIV care clinics of three primary health facilities and three referral hospitals in Moshi, Kilimanjaro, Tanzania. Children with acute illnesses, medication switch in the 6 months before the study visit, and any history of brain injury or developmental delay before cART initiation were excluded. All interviews and assessments were done by trained local research nurses under the supervision of a medical doctor. The primary outcomes, competence and psychopathology, were measured with the Child Behavior Checklist. We used ANCOVA to assess differences between groups. This study is registered with ClinicalTrials.gov, number NCT03227653.
Between June 19, 2017, and Dec 14, 2017, 141 children were analysed, of whom 72 (51%) used efavirenz-based cART and 69 (49%) used non-efavirenz-based cART. After controlling for age, sex, and clinical and demographic confounders, we observed lower competence (adjusted mean difference -2·43 [95% CI -4·19 to -0·67], p=0·0071), largely driven by lower school performance scores (adjusted mean difference -0·91 [-1·42 to -0·40], p=0·00055), in the efavirenz group than in the non-efavirenz group. More total (adjusted mean difference 5·96 [95% CI -1·12 to 13·04], p=0·098) and internalising (adjusted mean difference 2·00 [-0·29 to 4·29], p=0·086) behavioural problems were seen in the efavirenz group than in the non-efavirenz group, although these findings were non-significant. No differences were found in externalising problems (adjusted mean difference 0·78 [95% CI -1·55 to 3·11], p=0·51).
Our results suggest that treatment with efavirenz in children is associated with a mild increase in neuropsychiatric symptoms, especially in children who receive doses higher than or equal to the WHO recommended doses for efavirenz. Clinical awareness and adequate follow-up of neuropsychiatric symptoms in efavirenz in children remain warranted.
Aidsfonds, Radboud University Medical Center.
依非韦伦常用于治疗感染 HIV 的儿童，但对于其神经精神副作用风险知之甚少。我们旨在比较坦桑尼亚基于依非韦伦和非依非韦伦方案的儿童的能力（社会参与、活动和学业表现）和精神病理学（内化和外化问题）、认知表现（智力和工作记忆）和依从性。
在这项多中心、横断面、观察性研究中，我们纳入了来自坦桑尼亚莫希的三家初级保健机构和三家转诊医院的 HIV 护理诊所，连续纳入了年龄在 6-12 岁之间、接受至少 6 个月联合抗逆转录病毒治疗（cART）且病毒载量低于 1000 拷贝/毫升的 HIV 感染儿童。患有急性疾病、在研究就诊前 6 个月内药物更换以及在开始 cART 之前有任何脑损伤或发育迟缓史的儿童被排除在外。所有访谈和评估均由经过培训的当地研究护士在一名医生的监督下进行。主要结局是儿童行为检查表测量的能力和精神病理学。我们使用协方差分析（ANCOVA）来评估组间差异。本研究在 ClinicalTrials.gov 注册，编号为 NCT03227653。
2017 年 6 月 19 日至 2017 年 12 月 14 日，分析了 141 名儿童，其中 72 名（51%）使用依非韦伦为基础的 cART，69 名（49%）使用非依非韦伦为基础的 cART。在控制年龄、性别以及临床和人口统计学混杂因素后，我们观察到依非韦伦组的能力（调整后的平均差异-2.43 [95%CI-4.19 至-0.67]，p=0.0071）较低，主要表现为较低的学业成绩评分（调整后的平均差异-0.91 [-1.42 至-0.40]，p=0.00055）。与非依非韦伦组相比，依非韦伦组的总行为问题（调整后的平均差异 5.96 [95%CI-1.12 至 13.04]，p=0.098）和内化行为问题（调整后的平均差异 2.00 [-0.29 至 4.29]，p=0.086）更明显，尽管这些结果没有统计学意义。在外化行为问题方面没有差异（调整后的平均差异 0.78 [95%CI-1.55 至 3.11]，p=0.51）。
我们的研究结果表明，依非韦伦治疗儿童与轻度增加神经精神症状有关，尤其是在接受高于或等于世界卫生组织推荐的依非韦伦剂量的儿童中。仍需要对依非韦伦治疗儿童的神经精神症状进行临床意识和充分随访。
艾滋病基金、拉德堡德大学医学中心。
