Lazarus Erica, Nicol Simone, Frigati Lisa, Penazzato Martina, Cotton Mark F, Centeno-Tablante Elizabeth, Violari Avy, Nicol Liesl
From the *Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; †FAMCRU, Children's' Infectious Diseases Clinical Research Unit, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa; ‡World Health Organization, HIV Department, Treatment and Care Unit, Geneva, Switzerland; and §Centre for Evidence-based Health Care, Department of Interdisciplinary Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
Pediatr Infect Dis J. 2017 May;36(5):492-499. doi: 10.1097/INF.0000000000001481.
The World Health Organization identified a need for evidence to inform revision of second- and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second-line and subsequent ART regimens in children younger than 18 years.
We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov.
The search retrieved 1982 records. Eighteen studies provided efficacy data: 1 randomized controlled trial, 7 phase II trials, 5 prospective and 5 retrospective cohorts. Five studies evaluated regimens in children failing first-line ART, 4 in children with multidrug resistance and 9 in children with variable treatment experience. Only 10/18 studies reported week 48 or month 12 outcomes. The overall proportion of children with virologic suppression defined by study at week 48 was 61.8%. Although the randomized controlled trial had low risk of bias, outcomes were similar between groups because of highly active optimized background regimens. All phase II and prospective studies were judged to have moderate to high risk of bias. No study compared currently recommended lopinavir-based second-line regimens for nonnucleoside reverse transcriptase inhibitor failures to other non-nonnucleoside reverse transcriptase inhibitor regimens head-to-head.
We found no evidence comparing current World Health Organization-recommended second- and third-line ART regimens with regimens including drugs of interest: raltegravir, darunavir, etravirine and atazanavir. Randomized controlled trials or prospective cohort studies with comparator arms, and bridging studies, ideally conducted in resource-limited settings, are required to guide future recommendations.
世界卫生组织认为有必要获取证据，以指导对接受抗逆转录病毒治疗（ART）失败儿童的二线和三线ART方案进行修订。我们对所有关于18岁以下儿童二线及后续ART方案的现有文献进行了深入的范围综述。
我们全面检索了Cochrane对照试验中央注册库、MEDLINE、EMBASE、世界卫生组织国际临床试验注册平台和ClinicalTrials.gov，无语言或日期限制。
检索到1982条记录。18项研究提供了疗效数据：1项随机对照试验、7项II期试验、5项前瞻性队列研究和5项回顾性队列研究。5项研究评估了一线ART失败儿童的方案，4项研究评估了多药耐药儿童的方案，9项研究评估了治疗经验各异儿童的方案。18项研究中只有10项报告了第48周或第12个月的结果。根据研究定义，第48周病毒学抑制儿童的总体比例为61.8%。尽管随机对照试验的偏倚风险较低，但由于采用了高效优化的背景方案，各组间的结果相似。所有II期和前瞻性研究被判定具有中度至高偏倚风险。没有研究将目前推荐的基于洛匹那韦的二线方案用于非核苷类逆转录酶抑制剂失败的情况与其他非核苷类逆转录酶抑制剂方案进行直接对比。
我们没有发现将世界卫生组织目前推荐的二线和三线ART方案与包含感兴趣药物（雷特格韦、达芦那韦、依曲韦林和阿扎那韦）的方案进行比较的证据。需要进行有对照臂的随机对照试验或前瞻性队列研究，以及衔接性研究，最好在资源有限的环境中进行，以指导未来的建议。
