博茨瓦纳结核病筛查和留用干预对早期抗逆转录病毒治疗死亡率的影响：一项阶梯式楔形集群随机试验。

Effect of tuberculosis screening and retention interventions on early antiretroviral therapy mortality in Botswana: a stepped-wedge cluster randomized trial.

机构信息

Division of Global HIV & TB, Centers for Disease Control and Prevention, Atlanta, USA.

Center for Global Health, U.S. Centers for Disease Control and Prevention (CDC), Lilongwe, Malawi.

出版信息

BMC Med. 2020 Feb 11;18(1):19. doi: 10.1186/s12916-019-1489-0.

DOI:10.1186/s12916-019-1489-0

PMID:32041583

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7011529/

Abstract

BACKGROUND

Undiagnosed tuberculosis (TB) remains the most common cause of HIV-related mortality. Xpert MTB/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality.

METHODS

At 22 clinics, ART enrollees > 12 years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation.

RESULTS

We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184/μL in SOC, 246/μL in EC, and 241/μL in EC+X). By 6 months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61-0.97, p = 0.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees.

CONCLUSIONS

Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed.

TRIAL REGISTRATION

Retrospectively registered: ClinicalTrials.gov (NCT02538952).

摘要

背景

未确诊的结核病（TB）仍然是导致 HIV 相关死亡的最常见原因。Xpert MTB/RIF（Xpert）正在全球范围内推出，以提高结核病诊断能力。然而，之前的 Xpert 影响试验报告称，卫生系统的薄弱环节削弱了这一改进的诊断工具的影响。在博茨瓦纳分阶段推出 Xpert 的过程中，我们评估了一揽子干预措施的影响，其中包括（1）加强结核病病例发现（ICF）的额外支持，（2）对错过诊所预约的患者进行主动追踪以支持保留，以及（3）用 Xpert 替代痰涂片显微镜检查，对早期（6 个月）抗逆转录病毒治疗（ART）死亡率的影响。

方法

在 22 个诊所中，年龄在 12 岁以上的接受 ART 的患者有资格参与三个阶段：回顾性标准护理（SOC）、前瞻性强化护理（EC）和前瞻性 EC+Xpert（EC+X）阶段。EC 和 EC+X 阶段作为逐步楔形试验实施。EC 阶段的参与者接受 SOC 加干预包的组成部分 1（强化 ICF）和 2（主动追踪），而 EC+X 阶段的参与者接受 SOC 加干预包的所有三个组成部分。主要和次要目标是分别比较 SOC 和 EC+X 以及 EC 和 EC+X 阶段之间的全因 6 个月 ART 死亡率。我们使用适当的调整分析，考虑到研究设计，控制个体水平因素和设施内相关性的基线差异。

结果

我们共纳入了 14963 名符合条件的患者：SOC 组 8980 人，EC 组 1768 人，EC+X 组 4215 人。ART 患者的中位年龄为 35 岁，64%为女性。中位 CD4 细胞计数在 SOC 组低于后续阶段（SOC 组 184/μL，EC 组 246/μL，EC+X 组 241/μL）。在接受 ART 治疗 6 个月后，SOC 组有 461（5.3%）名、EC 组有 54（3.2%）名和 EC+X 组有 121（3.0%）名患者死亡。与 SOC 相比，EC+X 组的 6 个月死亡率较低（调整后的危险比为 0.77；95%置信区间为 0.61-0.97，p=0.029）。与 EC 组相比，EC+X 组的 6 个月死亡率相似。