Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA.
Cochrane Database Syst Rev. 2021 Aug 20;8(8):CD014641. doi: 10.1002/14651858.CD014641.
BACKGROUND: Tuberculosis is the primary cause of hospital admission in people living with HIV, and the likelihood of death in the hospital is unacceptably high. The Alere Determine TB LAM Ag test (AlereLAM) is a point-of-care test and the only lateral flow lipoarabinomannan assay (LF-LAM) assay currently commercially available and recommended by the World Health Organization (WHO). A 2019 Cochrane Review summarised the diagnostic accuracy of LF-LAM for tuberculosis in people living with HIV. This systematic review assesses the impact of the use of LF-LAM (AlereLAM) on mortality and other patient-important outcomes. OBJECTIVES: To assess the impact of the use of LF-LAM (AlereLAM) on mortality in adults living with HIV in inpatient and outpatient settings. To assess the impact of the use of LF-LAM (AlereLAM) on other patient-important outcomes in adults living with HIV, including time to diagnosis of tuberculosis, and time to initiation of tuberculosis treatment. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded (Web of Science), BIOSIS Previews, Scopus, LILACS; ProQuest Dissertations and Theses; ClinicalTrials.gov; and the WHO ICTRP up to 12 March 2021. SELECTION CRITERIA: Randomized controlled trials that compared a diagnostic intervention including LF-LAM with diagnostic strategies that used smear microscopy, mycobacterial culture, a nucleic acid amplification test such as Xpert MTB/RIF, or a combination of these tests. We included adults (≥ 15 years) living with HIV. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility, extracted data, and analysed risk of bias using the Cochrane tool for assessing risk of bias in randomized studies. We contacted study authors for clarification as needed. We used risk ratio (RR) with 95% confidence intervals (CI). We used a fixed-effect model except in the presence of clinical or statistical heterogeneity, in which case we used a random-effects model. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included three trials, two in inpatient settings and one in outpatient settings. All trials were conducted in sub-Saharan Africa and assessed the impact of diagnostic strategies that included LF-LAM on mortality when the test was used in conjunction with other tuberculosis diagnostic tests or clinical assessment for clinical decision-making in adults living with HIV. Inpatient settings In inpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy likely reduces mortality in people living with HIV at eight weeks compared to routine tuberculosis diagnostic testing without LF-LAM (pooled RR 0.85, 95% CI 0.76 to 0.94; 5102 participants, 2 trials; moderate-certainty evidence). That is, people living with HIV who received LF-LAM had 15% lower risk of mortality. The absolute effect was 34 fewer deaths per 1000 (from 14 fewer to 55 fewer). In inpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy probably results in a slight increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF-LAM (pooled RR 1.26, 95% CI 0.94 to 1.69; 5102 participants, 2 trials; moderate-certainty evidence). Outpatient settings In outpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy may reduce mortality in people living with HIV at six months compared to routine tuberculosis diagnostic testing without LF-LAM (RR 0.89, 95% CI 0.71 to 1.11; 2972 participants, 1 trial; low-certainty evidence). Although this trial did not detect a difference in mortality, the direction of effect was towards a mortality reduction, and the effect size was similar to that in inpatient settings. In outpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy may result in a large increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF-LAM (RR 5.44, 95% CI 4.70 to 6.29, 3022 participants, 1 trial; low-certainty evidence). Other patient-important outcomes Assessment of other patient-important and implementation outcomes in the trials varied. The included trials demonstrated that a higher proportion of people living with HIV were able to produce urine compared to sputum for tuberculosis diagnostic testing; a higher proportion of people living with HIV were diagnosed with tuberculosis in the group that received LF-LAM; and the incremental diagnostic yield was higher for LF-LAM than for urine or sputum Xpert MTB/RIF. AUTHORS' CONCLUSIONS: In inpatient settings, the use of LF-LAM as part of a tuberculosis diagnostic testing strategy likely reduces mortality and probably results in a slight increase in tuberculosis treatment initiation in people living with HIV. The reduction in mortality may be due to earlier diagnosis, which facilitates prompt treatment initiation. In outpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy may reduce mortality and may result in a large increase in tuberculosis treatment initiation in people living with HIV. Our results support the implementation of LF-LAM to be used in conjunction with other WHO-recommended tuberculosis diagnostic tests to assist in the rapid diagnosis of tuberculosis in people living with HIV.
背景:结核病是导致艾滋病毒感染者住院的主要原因,医院内死亡的可能性非常高。Alere Determine TB LAM Ag 检测(AlereLAM)是一种即时检测方法,也是目前唯一商业化并得到世界卫生组织(WHO)推荐的侧向流脂阿拉伯甘露聚糖检测(LF-LAM)。2019 年 Cochrane 综述总结了 LF-LAM 对艾滋病毒感染者结核病的诊断准确性。本系统评价评估了 LF-LAM(AlereLAM)的使用对死亡率和其他患者重要结局的影响。
目的:评估 LF-LAM(AlereLAM)在住院和门诊环境中对艾滋病毒感染者死亡率的影响。评估 LF-LAM(AlereLAM)的使用对艾滋病毒感染者其他患者重要结局的影响,包括结核病的诊断时间和结核病治疗的开始时间。
检索方法:我们检索了 Cochrane 传染病组专业注册库;Cochrane 中央对照试验注册库(CENTRAL);MEDLINE(PubMed);Embase(Ovid);科学引文索引扩展版(Web of Science)、BIOSIS 预览、Scopus、LILACS;ProQuest 学位论文和论文;ClinicalTrials.gov;以及世界卫生组织国际临床试验注册平台(WHO ICTRP)截至 2021 年 3 月 12 日。
选择标准:比较包括 LF-LAM 的诊断干预与使用显微镜检查、分枝杆菌培养、Xpert MTB/RIF 等核酸扩增试验或这些试验组合的诊断策略的随机对照试验。我们纳入了(≥15 岁)艾滋病毒感染者。
数据收集和分析:两名综述作者独立评估试验的入选情况、提取数据,并使用 Cochrane 工具评估随机研究的偏倚风险。我们根据需要联系了研究作者以获得澄清。我们使用风险比(RR)及其 95%置信区间(CI)。除非存在临床或统计学异质性,否则我们使用固定效应模型,否则我们使用随机效应模型。我们使用 GRADE 评估证据的确定性。
主要结果:我们纳入了三项试验,其中两项在住院环境中进行,一项在门诊环境中进行。所有试验均在撒哈拉以南非洲进行,评估了在艾滋病毒感染者中使用包括 LF-LAM 的诊断策略对死亡率的影响,当该检测与其他结核病诊断检测或临床评估结合用于临床决策时。住院环境在住院环境中,与不使用 LF-LAM 的常规结核病诊断检测相比,LF-LAM 检测作为结核病诊断策略的一部分可能降低艾滋病毒感染者在八周时的死亡率(合并 RR 0.85,95%CI 0.76 至 0.94;5102 名参与者,2 项试验;中等确定性证据)。也就是说,接受 LF-LAM 检测的艾滋病毒感染者的死亡率降低了 15%。绝对效应为每 1000 人减少 34 例死亡(从减少 14 例到减少 55 例)。在住院环境中,与不使用 LF-LAM 的常规结核病诊断检测相比,LF-LAM 检测作为结核病诊断策略的一部分可能会导致接受 LF-LAM 检测的艾滋病毒感染者开始接受结核病治疗的比例略有增加(合并 RR 1.26,95%CI 0.94 至 1.69;5102 名参与者,2 项试验;中等确定性证据)。门诊环境在门诊环境中,与不使用 LF-LAM 的常规结核病诊断检测相比,LF-LAM 检测作为结核病诊断策略的一部分可能会降低艾滋病毒感染者在六个月时的死亡率(RR 0.89,95%CI 0.71 至 1.11;2972 名参与者,1 项试验;低确定性证据)。尽管该试验未检测到死亡率的差异,但效应方向是死亡率降低,且效应大小与住院环境相似。在门诊环境中,与不使用 LF-LAM 的常规结核病诊断检测相比,LF-LAM 检测作为结核病诊断策略的一部分可能会导致接受 LF-LAM 检测的艾滋病毒感染者开始接受结核病治疗的比例大幅增加(RR 5.44,95%CI 4.70 至 6.29,3022 名参与者,1 项试验;低确定性证据)。其他患者重要结局在试验中评估的其他患者重要和实施结局各不相同。纳入的试验表明,与痰检测相比,更多的艾滋病毒感染者能够产生尿液进行结核病检测;接受 LF-LAM 检测的艾滋病毒感染者中有更高比例被诊断为结核病;与尿液或痰 Xpert MTB/RIF 相比,LF-LAM 的增量诊断效果更高。
作者结论:在住院环境中,LF-LAM 作为结核病诊断检测策略的一部分的使用可能会降低死亡率,并可能导致艾滋病毒感染者开始接受结核病治疗的比例略有增加。死亡率的降低可能是由于更早的诊断,从而促进了及时的治疗开始。在门诊环境中,LF-LAM 检测作为结核病诊断策略的一部分的使用可能会降低死亡率,并可能导致艾滋病毒感染者开始接受结核病治疗的比例大幅增加。我们的研究结果支持实施 LF-LAM,与其他世卫组织推荐的结核病诊断检测一起使用,以协助快速诊断艾滋病毒感染者中的结核病。
Cochrane Database Syst Rev. 2021-8-20
Cochrane Database Syst Rev. 2016-5-10
Cochrane Database Syst Rev. 2022-2-1
Cochrane Database Syst Rev. 2021-5-6
Cochrane Database Syst Rev. 2019-10-21
Cochrane Database Syst Rev. 2018-8-27
Cochrane Database Syst Rev. 2020-8-27
Cochrane Database Syst Rev. 2021-1-15
PLOS Glob Public Health. 2024-7-23
ERJ Open Res. 2024-7-22
PLOS Glob Public Health. 2023-2-22
PLOS Glob Public Health. 2022-7-19
Cochrane Database Syst Rev. 2021-5-6
Cochrane Database Syst Rev. 2021-1-15
Cochrane Database Syst Rev. 2020-8-27
N Engl J Med. 2020-6-18