PDF(Pubmed)
Abstract：
Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in children. We conducted a systematic review to assess the effectiveness and safety of dolutegravir and raltegravir in children and adolescents living with HIV, aged 0-19 years.
Sources included MEDLINE, Embase, the Cochrane Library, clinical trial registries, abstracts from key conferences and reference list searching. Observational studies and clinical trials published January 2009-March 2021 were eligible. Outcomes included efficacy/effectiveness (CD4 counts and viral load) and/or safety outcomes (mortality, grade 3/4 adverse events and treatment discontinuation) through 6 months or more post-treatment initiation. Risk of bias was assessed using previously published tools appropriate for the study design. Narrative syntheses were conducted.
In total, 3626 abstracts and 371 papers were screened. Eleven studies, including 2330 children/adolescents, reported data on dolutegravir: one randomized controlled trial (RCT; low risk of bias), one single-arm trial (unclear risk of bias) and nine cohort studies (three low risk of bias, two unclear risk and four high risk). Ten studies, including 649 children/adolescents receiving raltegravir, were identified: one RCT (low risk of bias), one single-arm trial (low risk of bias) and eight cohort studies (four low risk of bias, three unclear risk and one high risk). Viral suppression levels in children/adolescents at 12 months were high (>70%) in most studies assessing dolutegravir (mostly second- or subsequent-line, or mixed treatment lines), and varied from 42% (5/12) to 83% (44/53) at 12 months in studies assessing raltegravir (mostly second- or subsequent-line). Across all studies assessing dolutegravir or raltegravir, grade 3/4 adverse events (clinical and/or laboratory) were reported in 0-50% of subjects, few resulted in discontinuation, few were drug related and no deaths were attributed to either drug.
These reassuring findings suggest that dolutegravir and raltegravir are effective and safe as preferred regimens in children and adolescents living with HIV. With the rollout of dolutegravir in paediatric populations already underway, it is critical that data are collected on safety and effectiveness in infants, children and adolescents, including on longer-term outcomes, such as weight and metabolic changes.
Sources included MEDLINE, Embase, the Cochrane Library, clinical trial registries, abstracts from key conferences and reference list searching. Observational studies and clinical trials published January 2009-March 2021 were eligible. Outcomes included efficacy/effectiveness (CD4 counts and viral load) and/or safety outcomes (mortality, grade 3/4 adverse events and treatment discontinuation) through 6 months or more post-treatment initiation. Risk of bias was assessed using previously published tools appropriate for the study design. Narrative syntheses were conducted.
In total, 3626 abstracts and 371 papers were screened. Eleven studies, including 2330 children/adolescents, reported data on dolutegravir: one randomized controlled trial (RCT; low risk of bias), one single-arm trial (unclear risk of bias) and nine cohort studies (three low risk of bias, two unclear risk and four high risk). Ten studies, including 649 children/adolescents receiving raltegravir, were identified: one RCT (low risk of bias), one single-arm trial (low risk of bias) and eight cohort studies (four low risk of bias, three unclear risk and one high risk). Viral suppression levels in children/adolescents at 12 months were high (>70%) in most studies assessing dolutegravir (mostly second- or subsequent-line, or mixed treatment lines), and varied from 42% (5/12) to 83% (44/53) at 12 months in studies assessing raltegravir (mostly second- or subsequent-line). Across all studies assessing dolutegravir or raltegravir, grade 3/4 adverse events (clinical and/or laboratory) were reported in 0-50% of subjects, few resulted in discontinuation, few were drug related and no deaths were attributed to either drug.
These reassuring findings suggest that dolutegravir and raltegravir are effective and safe as preferred regimens in children and adolescents living with HIV. With the rollout of dolutegravir in paediatric populations already underway, it is critical that data are collected on safety and effectiveness in infants, children and adolescents, including on longer-term outcomes, such as weight and metabolic changes.
摘要：
到2020年，全球约有170万儿童感染了艾滋病毒。两种整合酶链转移抑制剂，dolutegravir和raltegravir,越来越多地用于儿童。我们进行了系统评价，以评估dolutegravir和raltegravir在感染艾滋病毒的儿童和青少年中的有效性和安全性，0-19岁。
来源包括MEDLINE，Embase,Cochrane图书馆,临床试验登记处，摘要从关键会议和参考列表搜索。2009年1月至2021年3月发表的观察性研究和临床试验符合资格。结果包括疗效/有效性（CD4计数和病毒载量）和/或安全性结果（死亡率，3/4级不良事件和治疗终止）至治疗开始后6个月或更长时间。使用以前发表的适合研究设计的工具评估偏倚风险。进行了叙事综合。
总共，筛选了3626篇摘要和371篇论文。11项研究,包括2330名儿童/青少年，关于dolutegravir的报告数据：一项随机对照试验（RCT；低偏倚风险），一项单臂试验(不清楚偏倚风险)和九项队列研究(三项低偏倚风险,两个不清楚的风险和四个高风险)。十项研究，包括649名接受拉特格韦治疗的儿童/青少年，确定：一项RCT(低偏倚风险)，一项单臂试验(低偏倚风险)和八项队列研究(四项低偏倚风险,三个不清楚的风险和一个高风险)。在大多数评估dolutegravir的研究中，儿童/青少年在12个月时的病毒抑制水平很高（>70％）（主要是二线或后续线，或混合处理线)，在评估raltegravir（主要是二线或后续线）的研究中，在12个月时从42％（5/12）到83％（44/53）变化。在所有评估dolutegravir或raltegravir的研究中，在0-50%的受试者中报告了3/4级不良事件(临床和/或实验室),很少导致停药，很少有人与药物有关，没有死亡归因于这两种药物。
这些令人放心的研究结果表明，dolutegravir和raltegravir作为HIV感染儿童和青少年的首选治疗方案是有效和安全的。随着dolutegravir在儿科人群中的推广已经开始，收集有关婴儿安全性和有效性的数据至关重要，儿童和青少年,包括长期结果，如体重和代谢变化。
来源包括MEDLINE，Embase,Cochrane图书馆,临床试验登记处，摘要从关键会议和参考列表搜索。2009年1月至2021年3月发表的观察性研究和临床试验符合资格。结果包括疗效/有效性（CD4计数和病毒载量）和/或安全性结果（死亡率，3/4级不良事件和治疗终止）至治疗开始后6个月或更长时间。使用以前发表的适合研究设计的工具评估偏倚风险。进行了叙事综合。
总共，筛选了3626篇摘要和371篇论文。11项研究,包括2330名儿童/青少年，关于dolutegravir的报告数据：一项随机对照试验（RCT；低偏倚风险），一项单臂试验(不清楚偏倚风险)和九项队列研究(三项低偏倚风险,两个不清楚的风险和四个高风险)。十项研究，包括649名接受拉特格韦治疗的儿童/青少年，确定：一项RCT(低偏倚风险)，一项单臂试验(低偏倚风险)和八项队列研究(四项低偏倚风险,三个不清楚的风险和一个高风险)。在大多数评估dolutegravir的研究中，儿童/青少年在12个月时的病毒抑制水平很高（>70％）（主要是二线或后续线，或混合处理线)，在评估raltegravir（主要是二线或后续线）的研究中，在12个月时从42％（5/12）到83％（44/53）变化。在所有评估dolutegravir或raltegravir的研究中，在0-50%的受试者中报告了3/4级不良事件(临床和/或实验室),很少导致停药，很少有人与药物有关，没有死亡归因于这两种药物。
这些令人放心的研究结果表明，dolutegravir和raltegravir作为HIV感染儿童和青少年的首选治疗方案是有效和安全的。随着dolutegravir在儿科人群中的推广已经开始，收集有关婴儿安全性和有效性的数据至关重要，儿童和青少年,包括长期结果，如体重和代谢变化。
