Consultants to the World Health Organization, Geneva, Switzerland.
International AIDS Society, Geneva, Switzerland.
J Int AIDS Soc. 2023 Feb;26(2):e26037. doi: 10.1002/jia2.26037.
Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV.
We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009-March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0-19 years.
Overall 3626 abstracts and 371 full papers were screened. Four single-arm, innovator-funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment-experienced and virally suppressed children or adolescents. One trial also included treatment-naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment-naïve participants were virally suppressed (one trial). Among treatment-experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug-related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug-related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z-score (height- and age-adjusted) from baseline to 48 weeks was -0.12 (interquartile range [IQR] -0.46, 0.17) to 0.05 (IQR not reported) for spine, and -0.09 (IQR -0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight-for-age z-scores increased by 0.25 from baseline to 48 weeks.
Four single-arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF-containing regimens over 24-48 weeks. However, further comparative and longer-term safety data are needed in children and adolescents, including on weight and metabolic changes.
替诺福韦艾拉酚胺（TAF）已获批准用于固定剂量复方片剂的儿科用途，但在儿童中的疗效和安全性数据有限。我们进行了一项系统评价，评估了 TAF 在感染 HIV 的婴儿、儿童和青少年中的疗效/有效性和安全性。
我们检索了 MEDLINE、Embase、Cochrane 图书馆、临床试验注册处、参考文献列表和相关会议，以确定 2009 年 1 月至 2021 年 3 月发表的文献。我们纳入了评估 TAF 治疗≥6 个月的疗效/有效性或安全性的临床试验和观察性研究，参与者年龄为 0-19 岁。
共筛选了 3626 篇摘要和 371 篇全文。确定了四项单臂、原研药资助的试验（341 名参与者）和这些试验的汇总分析。所有四项试验均纳入了治疗经验丰富且病毒载量得到抑制的儿童或青少年。一项试验还纳入了基线病毒载量>1000 拷贝/ml 的治疗初治青少年。由于研究设计的缺失，一项研究的偏倚风险被评为低（所有会议报告），其他三项研究的偏倚风险被评为不确定。在 48 周时，46/50 名治疗初治的参与者病毒载量得到抑制（一项试验）。在病毒载量得到抑制的治疗经验丰富的参与者中，214 名参与者病毒载量得到抑制。在所有研究中，有 1 例 3/4 级不良事件被认为与药物相关（中度虹膜炎）。有 3 例因不良事件停药（2 级焦虑和失眠、1 级虹膜炎[与药物相关]和 1 级肺结核[与治疗无关]）。四项研究中有 1 例意外死亡。在 223 名参与者的汇总分析中，从基线到 48 周时，骨矿物质密度 z 分数（身高和年龄校正）中位数变化为脊柱从-0.12（四分位距[IQR] -0.46，0.17）到-0.05（IQR 未报告），全身除头部从-0.09（IQR -0.33，0.07）到-0.09（IQR 未报告）。体重与年龄的 z 分数从基线增加到 48 周时增加了 0.25。
在这项系统评价中确定了四项单臂试验，初步证据表明，在 24-48 周期间，接受 TAF 治疗的儿童和青少年病毒抑制良好，无明显安全性问题。然而，儿童和青少年仍需要进一步的比较和长期安全性数据，包括体重和代谢变化。
