Fortuin-de Smidt Melony, de Waal Reneé, Cohen Karen, Technau Karl-Günter, Stinson Kathryn, Maartens Gary, Boulle Andrew, Igumbor Ehimario U, Davies Mary-Ann
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
PLoS One. 2017 Feb 13;12(2):e0169762. doi: 10.1371/journal.pone.0169762. eCollection 2017.
There are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010.
We included children (<16 years at ART initiation) who initiated ≥3 antiretrovirals between 2004-2014 with ≥1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity.
We included 3579 children with median follow-up duration of 41 months (IQR 14-72). At ART initiation, median age was 44 months (IQR 13-89) and median CD4 percent was 15% (IQR 9-21%). At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%), treatment failure (18%), treatment simplification (5%), drug interactions (3%), and other or unspecified reasons (18%). The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2-55.4), 1.6 (0.5-4.8), 2.0 (1.2-3.3), and 1.3 (0.6-2.8) per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively.
While stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health Organization recommendation to replace stavudine with abacavir or zidovudine in paediatric first-line ART regimens in order to improve paediatric first-line ART durability.
儿科抗逆转录病毒药物的选择有限。了解不同抗逆转录病毒药物在儿童中的长期安全性和持久性对于优化艾滋病毒感染儿童的管理以及确定儿科治疗方案中替代药物的估计需求非常重要。我们描述了南非两个抗逆转录病毒治疗项目中儿童一线抗逆转录病毒治疗（ART）的持久性以及停药原因，自2004年以来，洛匹那韦/利托那韦被推荐用于3岁以下儿童，2010年阿巴卡韦取代司他夫定成为首选的核苷类逆转录酶抑制剂。
我们纳入了2004年至2014年间开始接受≥3种抗逆转录病毒药物治疗且至少有1次ART随访的儿童（开始ART时年龄<16岁）。我们使用Kaplan-Meier分析估计首次抗逆转录病毒停药的发生率。我们使用竞争风险分析确定抗逆转录病毒停药的原因。我们使用Cox回归确定与治疗限制性毒性相关的因素。
我们纳入了3579名儿童，中位随访时间为41个月（四分位间距14 - 72个月）。开始ART时，中位年龄为44个月（四分位间距13 - 89个月），CD4百分比中位数为15%（四分位间距9 - 21%）。在接受ART治疗3年和5年时，分别有72%和26%的儿童仍在使用初始治疗方案。到接受ART治疗5年时，最常见的停药原因是毒性（32%）、治疗失败（18%）、治疗简化（5%）、药物相互作用（3%）以及其他或未明确说明的原因（18%）。司他夫定、阿巴卡韦、依非韦伦和洛匹那韦/利托那韦每1000患者年的治疗限制性毒性发生率分别为50.6（95%置信区间46.2 - 55.4）、1.6（0.5 - 4.8）、2.0（1.2 - 3.3）和1.3（0.6 - 2.8）。
虽然司他夫定与治疗限制性毒性的高风险相关，但阿巴卡韦、洛匹那韦/利托那韦和依非韦伦耐受性良好。这支持了世界卫生组织关于在儿科一线ART方案中用阿巴卡韦或齐多夫定替代司他夫定以提高儿科一线ART持久性的建议。
