First-line antiretroviral drug discontinuations in children

IntroductionThere 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 MethodsWe included children (ResultsWe 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.ConclusionsWhile 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.引言：目前儿科可用的抗逆转录病毒药物选择十分有限。明确不同抗逆转录病毒药物在儿童群体中的长期安全性与治疗持久性，对于优化HIV感染儿童的临床诊疗方案、预估儿科抗逆转录病毒治疗方案中替代药物的需求至关重要。本研究针对南非两项抗逆转录病毒治疗（antiretroviral therapy, ART）项目中的儿童群体，分析其一线抗逆转录病毒治疗的持久性及停药原因，上述项目均推荐洛匹那韦/利托那韦（lopinavir/ritonavir）用于儿童患者。方法：本研究纳入儿童HIV感染者。结果：本研究共纳入3579名儿童，中位随访时长为41个月（四分位间距IQR：14~72个月）。启动抗逆转录病毒治疗时，儿童的中位年龄为44个月（IQR：13~89个月），中位CD4百分比为15%（IQR：9~21%）。接受抗逆转录病毒治疗满3年和5年时，分别有72%和26%的儿童仍维持初始治疗方案。至治疗满5年时，最常见的停药原因为药物毒性（32%）、治疗失败（18%）、治疗方案简化（5%）、药物相互作用（3%）及其他/未明确原因（18%）。司他夫定（stavudine）、阿巴卡韦（abacavir）、依非韦伦（efavirenz）及洛匹那韦/利托那韦（lopinavir/ritonavir）的治疗限制性毒性发生率分别为每1000患者年50.6（95%置信区间：46.2~55.4）、1.6（95%置信区间：0.5~4.8）、2.0（95%置信区间：1.2~3.3）及1.3（95%置信区间：0.6~2.8）。结论：尽管司他夫定与较高的治疗限制性毒性风险相关，但阿巴卡韦、洛匹那韦/利托那韦及依非韦伦的耐受性良好。该研究结果支持世界卫生组织（World Health Organization, WHO）的推荐：在儿科一线抗逆转录病毒治疗方案中，采用阿巴卡韦或齐多夫定（zidovudine）替代司他夫定，以提升儿科一线抗逆转录病毒治疗的持久性。