Supplementary materials: Comparative safety of B/F/TAF versus other antiretroviral therapy regimens for treatment-na¨ıve people with HIV-1: a systematic literature review and network meta-analysis

<b>These are peer-reviewed supplementary materials for the article</b><b> </b><b>'</b><b>Comparative safety of B/F/TAF versus </b><b>other antiretroviral therapy regimens for </b><b>treatment-na¨ıve people with HIV-1: a </b><b>systematic literature review and network </b><b>meta-analysis</b><b>'</b><b> </b><b>published in the</b><b> </b><b><i>Journal of Comparative Effectiveness Research</i></b><b>.</b><b>SLR Methodology</b><b>NMA Methodology</b><b>Model Specification</b><b>Table S1: </b>Search terms for MEDLINE<b>Table S2:</b> Eligibility Criteria, Using PICO Framework<b>Table S3: </b>Treatment regimens of interest for ITCs<b>Table S4: </b>Outcome Definitions (Week 48)<b>Table S5: </b>List of studies in the TN population excluded from the feasibility assessment<b>Table S6: </b>PRISMA-NMA Checklist<b>Table S7: </b>Summary of Week 48 NMA inputs for the studies included in the NMA<b>Table S8: </b>Study characteristics of included studies<b>Table S9:</b> Quality assessments of studies included in the NMA<b>Table S10: </b>Quality assessment of all studies included in the NMA<b>Table S11: </b>Summary of baseline demographic and clinical characteristics in included studies<b>Table S12: </b>NMA Results Summary Table at Week 48: Absolute Risk (95% CrI)<b>Table S13:</b> NMA Results Summary Table at Week 48: Mean SUCRA<b>Table S14: </b>NMA Results Summary Table at Week 48: Probability Best<b>Table S15: </b>Model Fit Statistics: TRAE at Week 48<b>Table S16: </b>Model Fit Statistics: Grade 3/4 TEAE at Week 48<b>Table S17:</b> Model Fit Statistics: Diarrhoea at Week 48<b>Table S18: </b>Model Fit Statistics: Nausea at Week 48<b>Table S19: </b>Model Fit Statistics: All-Cause Discontinuation at Week 48<b>Table S20: </b>Model Fit Statistics: Discontinuation due to AE at Week 48<b>Table S21: </b>Treatment-Emergent Resistance Mutations Reported at Week 48<b>Table S22: </b>NMA Results Summary Table at Week 96<b>References</b><b>Aim: </b>Bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) is a single-tablet regimen approved for the treatment of HIV-1 in treatment-naive (TN) and virologically suppressed people with HIV-1 (PWH). While the efficacy of antiretroviral therapy (ART) regimens in TN PWH is well established, regimen selection is often influenced by safety and tolerability concerns. This systematic literature review and network meta-analysis compares the safety outcomes of B/F/TAF with other ART regimens in TN PWH, addressing a key aspect of therapeutic decision-making. <b>Materials &amp; methods: </b>A systematic literature review was performed to identify phase III and IV RCTs assessing B/F/TAF and comparator regimens in TN adults (≥18 years) with HIV-1. MEDLINE, Embase, Cochrane Database of Systematic Reviews and CENTRAL databases were last searched on 14 June 2023. Study design, population and outcome definitions were evaluated to ensure consistency across studies. Bayesian network meta-analyses were conducted where feasible, following key methodological guidelines. <b>Results:</b> Nineteen studies were included in indirect comparisons following assessments of heterogeneity and network connectivity. B/F/TAF performed better than the majority of interventions in safety and tolerability outcomes, notably discontinuation due to adverse events (AEs), treatment-related AEs and nausea. Additionally, with comparable risk of experiencing grade 3/4 treatment-emergent AEs, diarrhea and all-cause discontinuation rates to other interventions, B/F/TAF was non-inferior to any other regimen for all outcomes. B/F/TAF typically outperformed interventions containing non-nucleoside reverse transcriptase inhibitor third agents in terms of treatment-related AEs, nausea, and discontinuation due to AEs, although treatment class effects were not estimated separately. <b>Conclusion: </b>This analysis highlights the favorable safety profile of B/F/TAF compared with other ART regimens in TN PWH, demonstrating that B/F/TAF remains a safe and welltolerated ART option for most TN PWH.

本文为发表于《比较效果研究杂志》（*Journal of Comparative Effectiveness Research*）的论文《针对HIV-1初治人群的B/F/TAF与其他抗反转录病毒治疗方案安全性比较：系统文献综述与网络meta分析》的同行评议补充材料。
系统文献综述方法学
网络meta分析方法学
模型设定
表S1：MEDLINE数据库检索词
表S2：采用PICO框架制定的纳入排除标准
表S3：间接治疗比较（ITC）关注的治疗方案
表S4：第48周结局指标定义
表S5：可行性评估排除的HIV-1初治人群相关研究列表
表S6：PRISMA-NMA检查表
表S7：纳入网络meta分析的研究第48周网络meta分析输入参数汇总表
表S8：纳入研究的特征信息
表S9：纳入网络meta分析研究的质量评估
表S10：纳入网络meta分析的全部研究的质量评估
表S11：纳入研究的基线人口学与临床特征汇总表
表S12：第48周网络meta分析结果汇总表：绝对风险（95%可信区间，95% CrI）
表S13：第48周网络meta分析结果汇总表：平均表面下累积排序概率值（mean surface under the cumulative ranking curve, mean SUCRA）
表S14：第48周网络meta分析结果汇总表：最优概率
表S15：第48周治疗突发不良事件（treatment-emergent adverse event, TRAE）模型拟合统计量
表S16：第48周3/4级治疗突发不良事件（treatment-emergent adverse event, TEAE）模型拟合统计量
表S17：第48周腹泻症状模型拟合统计量
表S18：第48周恶心症状模型拟合统计量
表S19：第48周全因停药模型拟合统计量
表S20：第48周因不良事件停药模型拟合统计量
表S21：第48周报告的治疗突发耐药突变
表S22：第96周网络meta分析结果汇总表
参考文献

研究目的：比克替拉韦、恩曲他滨与丙酚替诺福韦单片复方制剂（B/F/TAF）是获批用于治疗HIV-1初治人群及病毒学抑制HIV-1感染者的单片抗反转录病毒治疗方案。尽管抗反转录病毒治疗（antiretroviral therapy, ART）方案用于HIV-1初治人群的疗效已得到充分证实，但方案选择常受安全性与耐受性相关问题的影响。本系统文献综述与网络meta分析旨在比较B/F/TAF与其他ART方案在HIV-1初治人群中的安全性结局，为临床治疗决策提供关键依据。

材料与方法：本研究开展系统文献检索，以识别针对HIV-1初治成人（≥18岁）评估B/F/TAF及对照方案的Ⅲ期、Ⅳ期随机对照试验（randomized controlled trial, RCT）。检索时限截至2023年6月14日，检索数据库包括MEDLINE、Embase、Cochrane系统综述数据库及CENTRAL数据库。研究对研究设计、研究人群及结局指标定义进行统一评估，确保纳入研究的一致性。基于关键方法学指南，在可行性允许的前提下开展贝叶斯网络meta分析。

研究结果：经异质性与网络连通性评估后，共纳入19项研究用于间接比较。在安全性与耐受性结局方面，B/F/TAF的表现优于大多数干预措施，尤其是因不良事件（adverse event, AE）停药、治疗相关不良事件及恶心症状方面。此外，与其他干预措施相比，B/F/TAF在3/4级治疗突发不良事件、腹泻及全因停药率方面风险相当，在所有结局指标上均不劣于其他任何方案。尽管未单独估算治疗类别效应，但相较于含非核苷类反转录酶抑制剂（non-nucleoside reverse transcriptase inhibitor, NNRTI）作为第三组分的干预措施，B/F/TAF在治疗相关不良事件、恶心及因AE停药方面通常表现更优。

研究结论：本分析证实，相较于其他ART方案，B/F/TAF在HIV-1初治人群中具有更优异的安全性特征，表明B/F/TAF仍是多数HIV-1初治人群安全且耐受性良好的ART治疗选择。