Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Knowledge Translation Unit, University of Cape Town Lung Institute, Rondebosch, South Africa.
BMJ Open. 2021 Oct 25;11(10):e039462. doi: 10.1136/bmjopen-2020-039462.
To evaluate the definition of HIV virological outcomes in the literature and factors associated with outcomes and missing outcome data.
We conducted a methodological review of HIV RCTs using a search (2009-2019) of PubMed, Embase and the Cochrane Central Register of Controlled Trials.Only full-text, peer-reviewed, randomised controlled trials (RCTs) that measured virological outcomes in people living with HIV, and published in English were included.We extracted study details and outcomes. We used logistic regression to identify factors associated with a viral threshold ≤50 copies/mL and linear regression to identify factors associated with missing outcome data.
Our search yielded 5847 articles; 180 were included. A virological outcome was the primary outcome in 73.5% of studies. 89 studies (49.4%) used virological success. The remaining used change in viral load (VL) (33 studies, 18.3%); virological failure (59 studies, 32.8%); or virological rebound (9 studies, 5.0%). 96 studies (53.3%) set the threshold at ≤50 copies/mL; and 33.1% used multiple measures.Compared with government and privately funded studies, RCTs with industry funding (adjusted OR 6.39; 95% CI 2.15 to 19.00; p<0.01) were significantly associated with higher odds of using a VL threshold of ≤50 copies/mL. Publication year, intervention type, income level and number of patients were not associated with a threshold of ≤50 copies/mL. Trials with pharmacological interventions had less missing data (β=-11.04; 95% CI -20.02 to -1.87; p=0.02).
Country source of funding was associated with VL threshold choice and studies with pharmacological interventions had less missing data, which may in part explain heterogeneous virological outcomes across studies. Multiple measures of VL were not associated with missing data. The development of formal guidelines on virological outcome reporting in RCTs is needed.
评估文献中 HIV 病毒学结果的定义，以及与结果和缺失结果数据相关的因素。
我们对 HIV RCT 进行了方法学综述，使用了对 PubMed、Embase 和 Cochrane 对照试验中心注册库的搜索（2009-2019 年）。仅纳入了全文、同行评审、随机对照试验（RCT），这些试验在 HIV 感染者中测量了病毒学结果，并以英文发表。我们提取了研究细节和结果。我们使用逻辑回归来确定与病毒阈值≤50 拷贝/毫升相关的因素，使用线性回归来确定与缺失结果数据相关的因素。
我们的搜索产生了 5847 篇文章；纳入了 180 篇。73.5%的研究将病毒学结果作为主要结局。89 项研究（49.4%）使用了病毒学成功。其余的研究使用了病毒载量（VL）的变化（33 项研究，18.3%）；病毒学失败（59 项研究，32.8%）；或病毒学反弹（9 项研究，5.0%）。96 项研究（53.3%）将阈值设定为≤50 拷贝/毫升；33.1%使用了多种措施。与政府和私人资助的研究相比，有行业资助的 RCT（调整后的比值比 6.39；95%置信区间 2.15 至 19.00；p<0.01）与使用≤50 拷贝/毫升的 VL 阈值的可能性显著更高相关。研究年份、干预类型、收入水平和患者数量与≤50 拷贝/毫升的阈值无关。具有药理学干预的试验缺失数据较少（β=-11.04；95%置信区间-20.02 至-1.87；p=0.02）。
资金来源国与 VL 阈值选择相关，具有药理学干预的研究缺失数据较少，这可能部分解释了研究之间病毒学结果的异质性。VL 的多种测量方法与缺失数据无关。需要制定关于 RCT 中病毒学结果报告的正式指南。
