Saint-Lary Laura, Dassi Tchoupa Revegue Marc Harris, Jesson Julie, Renaud Françoise, Penazzato Martina, Townsend Claire L, O'Rourke John, Leroy Valériane
CERPOP, Inserm, Université de Toulouse, Université Paul Sabatier III, Toulouse, France.
Global HIV, Hepatitis and STIs Programme, World Health Organization, Geneva, Switzerland.
Front Pediatr. 2022 May 23;10:913105. doi: 10.3389/fped.2022.913105. eCollection 2022.
Atazanavir/ritonavir is recommended as a preferred second-line antiretroviral regimen in children older than 3 months, alternatively to lopinavir/ritonavir. We performed a systematic review to assess safety and effectiveness of atazanavir use in children and adolescents.
We searched observational studies and clinical trials on Web of Science, Embase and Cochrane CENTRAL database between 2009/01/01 and 2020/10/01; as well as grey literature. We extracted safety (adverse events, grade 3 or 4 adverse events, treatment discontinuation) and effectiveness (CD4 cell counts and HIV viral load) outcomes. We estimated weighted summary pooled incidence with corresponding 95% confidence intervals.
Out of the 1,085 records screened, we included five studies (one comparative cohort, three single phase 2-3 trial arms, one retrospective cohort) reporting 975 children and adolescents, of whom 56% (544) received atazanavir. Three studies reported all-cause treatment discontinuation rates, yielding a pooled incidence of 19% [15-22] at 12 months. The comparative cohort compared atazanavir to darunavir, with few grade 3-4 adverse events, except transient hyperbilirubinemia, occurring in half (92/188) of the atazanavir patients. No death occurred (two studies reporting). Four studies described increased CD4 cell counts and decreased HIV viral load at 6 or 12 months.
Few safety and effectiveness data were available for children and adolescents exposed to atazanavir. Transient grade 3-4 hyperbilirubinemia was the main adverse outcome reported. Immune and viral responses were descriptive. The use of atazanavir/ritonavir in children and adolescents needs further investigation, but remains a suitable option for a preferred second-line antiretroviral regimen.
CRD42022309230.
对于3个月以上儿童，阿扎那韦/利托那韦被推荐作为首选二线抗逆转录病毒治疗方案，可替代洛匹那韦/利托那韦。我们进行了一项系统评价，以评估阿扎那韦在儿童和青少年中的安全性和有效性。
我们检索了2009年1月1日至2020年10月1日期间Web of Science、Embase和Cochrane CENTRAL数据库中的观察性研究和临床试验；以及灰色文献。我们提取了安全性（不良事件、3级或4级不良事件、治疗中断）和有效性（CD4细胞计数和HIV病毒载量）结果。我们估计了加权汇总合并发病率及相应的95%置信区间。
在筛选的1085条记录中，我们纳入了五项研究（一项比较队列研究、三项单臂2-3期试验、一项回顾性队列研究），共报告了975名儿童和青少年，其中56%（544名）接受了阿扎那韦治疗。三项研究报告了全因治疗中断率，12个月时的合并发病率为19%[15-22]。比较队列研究将阿扎那韦与达芦那韦进行了比较，除了短暂性高胆红素血症外，3-4级不良事件较少，阿扎那韦组有一半（92/188）患者出现该症状。未发生死亡（两项研究报告）。四项研究描述了6个月或12个月时CD4细胞计数增加和HIV病毒载量降低。
关于暴露于阿扎那韦的儿童和青少年的安全性和有效性数据较少。短暂性3-4级高胆红素血症是报告的主要不良结局。免疫和病毒反应只是描述性的。阿扎那韦/利托那韦在儿童和青少年中的应用需要进一步研究，但仍是首选二线抗逆转录病毒治疗方案的合适选择。
CRD42022309230。
