Center for Epidemiology and Research in Population Health, Inserm U1295, Université de Toulouse, Université Paul Sabatier, Toulouse, France.
Center for Epidemiology and Research in Population Health, Inserm U1295, Université de Toulouse, Université Paul Sabatier, Toulouse, France.
Lancet Child Adolesc Health. 2022 Oct;6(10):692-704. doi: 10.1016/S2352-4642(22)00213-9. Epub 2022 Sep 2.
Abacavir is a nucleoside reverse transcriptase inhibitor recommended in paediatric HIV care. We assessed the safety and efficacy profile of abacavir used in first, second, or subsequent lines of treatment for infants, children, and adolescents living with HIV to inform 2021 WHO paediatric ART recommendations.
In this systematic review and meta-analysis, we included observational and experimental studies conducted in infants aged 0-1 year, children aged 1-10 years, and adolescents aged 10-19 years living with HIV; with data on safety or efficacy, or both, of abacavir-based antiretroviral therapy (ART); published in English or French between Jan 1, 2009, and Oct 1, 2020, plus an updated search to incorporate studies published between Oct 1, 2020, and May 15, 2022. Studies could be non-randomised or non-comparative and include patients who are treatment-naive or those who previously received abacavir (only if abacavir was combined with other ART). Case studies, studies in adults aged 18 years or older, and those assessing the effect of maternal ART exposure were excluded. We extracted data related to study identifier, study design, study period, setting, population characteristics, ART treatment, and safety (any hypersensitivity reaction, death, grade 3 or 4 adverse events, treatment discontinuation, any other morbidities, and serious adverse events), and efficacy outcomes (HIV viral load and CD4 counts reported at 6 and 12 months after ART initiation). Using random-effect models, we estimated weighted pooled incidence and relative risk (RR) of outcomes. The protocol is published in PROSPERO (CRD42022309230).
Of 1777 records identified, 1475 (83%) were screened after removing duplicates and a further 1421 (96%) were excluded. Of 54 full-text articles assessed for eligibility, 33 (61%) were excluded. Four records were identified from grey literature plus one duplicate from database searching, resulting in 24 studies included (two randomised controlled trials, one single-arm trial, 12 prospective cohorts, seven retrospective cohorts, and two cross-sectional studies). 19 studies described safety data and 15 described efficacy data. 18 (75%) studies were conducted in ART-naive participants. The risk of bias was considered moderate to high for most studies, and all outcomes had significant between-study heterogeneity. Data from 24 265 participants were included, of whom 7236 (30%) received abacavir. Abacavir hypersensitivity reaction was reported in nine (38%) studies, with an incidence ranging from 0·00% to 8·26% (I=85%; p<0·0001). The incidence of death (reported in seven studies) following abacavir treatment varied from 0·00% to 5·49% (I=58%; p=0·026). Viral suppression (<400 copies per mL) varied from 50% to 70% at 6 months (I=92%, p<0·0001) and from 57% to 78% at 12 months (I=88%, p<0·0001).
Toxic effects due to abacavir use remain rare and manageable. Despite scarce data on efficacy, this meta-analysis supports the use of abacavir as a preferred first-line regimen for infants and children living with HIV.
WHO.
阿巴卡韦是一种核苷逆转录酶抑制剂，推荐用于儿科艾滋病毒护理。我们评估了阿巴卡韦在治疗婴儿、儿童和青少年艾滋病毒感染者的一线、二线或后续治疗中的安全性和疗效，为 2021 年世卫组织儿科抗逆转录病毒治疗建议提供信息。
在这项系统评价和荟萃分析中，我们纳入了在年龄 0-1 岁的婴儿、年龄 1-10 岁的儿童和年龄 10-19 岁的青少年艾滋病毒感染者中进行的观察性和实验性研究；这些研究提供了基于阿巴卡韦的抗逆转录病毒治疗（ART）的安全性或疗效，或两者兼有；研究发表于 2009 年 1 月 1 日至 2020 年 10 月 1 日之间，英文或法文，另外还进行了一次更新搜索，纳入了 2020 年 10 月 1 日至 2022 年 5 月 15 日期间发表的研究。研究可以是非随机或非对照的，包括初治或既往接受过阿巴卡韦治疗的患者（只有当阿巴卡韦与其他 ART 联合使用时）。排除了病例研究、成人（18 岁及以上）研究以及评估母体 ART 暴露影响的研究。我们提取了与研究标识符、研究设计、研究期间、研究地点、人口特征、ART 治疗以及安全性（任何过敏反应、死亡、3 或 4 级不良事件、治疗中止、任何其他发病率和严重不良事件）和疗效结果（开始 ART 后 6 个月和 12 个月时报告的 HIV 病毒载量和 CD4 计数）相关的数据。使用随机效应模型，我们估计了结局的加权汇总发生率和相对风险（RR）。方案已在 PROSPERO（CRD42022309230）中发布。
在 1777 条记录中，有 1475 条（83%）在去除重复项后进行了筛选，另有 1421 条（96%）被排除。在 54 篇评估合格性的全文文章中，有 33 篇（61%）被排除。从灰色文献中确定了 4 条记录，从数据库搜索中又确定了 1 条重复记录，共纳入 24 项研究（2 项随机对照试验、1 项单臂试验、12 项前瞻性队列研究、7 项回顾性队列研究和 2 项横断面研究）。19 项研究描述了安全性数据，15 项研究描述了疗效数据。18 项（75%）研究在初治参与者中进行。大多数研究的偏倚风险被认为是中度至高度，所有结局均存在显著的研究间异质性。共纳入 24265 名参与者的数据，其中 7236 名（30%）接受了阿巴卡韦治疗。在 9 项研究中报告了阿巴卡韦过敏反应，发生率为 0·00%至 8·26%（I=85%；p<0·0001）。阿巴卡韦治疗后死亡的发生率（在 7 项研究中报告）从 0·00%到 5·49%不等（I=58%；p=0·026）。6 个月时病毒抑制率（<400 拷贝/毫升）从 50%到 70%不等（I=92%；p<0·0001），12 个月时从 57%到 78%不等（I=88%；p<0·0001）。
由于使用阿巴卡韦而产生的毒性作用仍然很少见且可管理。尽管关于疗效的数据稀缺，但这项荟萃分析支持将阿巴卡韦作为婴儿和儿童艾滋病毒感染者的首选一线方案。
世卫组织。
