Makerere University, Department of Medicine, College of Health Sciences, Kampala, Uganda.
Infectious Diseases Research Collaboration, Kampala, Uganda.
PLoS Med. 2024 Feb 20;21(2):e1004356. doi: 10.1371/journal.pmed.1004356. eCollection 2024 Feb.
Expanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies.
In a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion (≥11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher's exact test (two-sided α = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] p < 0.001), SAT (0.92; 97.5% CI [0.89, 0.94] p < 0.001), and Choice (0.93; 97.5% CI [0.91, 0.96] p < 0.001) arms. There was no difference in acceptance and completion between any 2 arms overall or in prespecified subgroup analyses based on sex, age, time on antiretroviral therapy, and history of prior treatment for TB or TB infection. Only 14 (0.8%) participants experienced an adverse event prompting discontinuation of 3HP. The main limitation of the study is that it was conducted in a single center. Multicenter studies are now needed to confirm the feasibility and generalizability of the facilitated 3HP delivery strategies in other settings.
Short-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers.
ClinicalTrials.gov NCT03934931.
扩大结核病（TB）预防的短程治疗方案的可及性，例如每周一次的异烟肼和利福平治疗 3 个月（3HP），对于降低 HIV 感染者（PLHIV）中的全球结核病负担至关重要。我们的主要假设是，通过优化交付策略以克服充分背景化的障碍，可以实现 3HP 的高水平接受和完成，并且当 PLHIV 在交付策略之间提供知情选择时，3HP 的接受和完成率将最高。
在一项实用的、单中心、3 臂、平行组随机试验中，乌干达坎帕拉的一家大型城市 HIV 诊所接受护理的 PLHIV 被随机分配（1:1:1）接受 3HP 通过促进直接观察治疗（DOT）、促进自我管理治疗（SAT）或使用共享决策辅助工具在促进 DOT 和促进 SAT 之间进行知情选择。我们使用精确二项置信区间（CI）评估了治疗开始后 16 周内接受和完成（3HP 至少 11 剂）的主要结局。我们使用 Fisher 精确检验（双侧α=0.025）比较了组间的比例。试验研究人员通过研究臂对主要和次要结局进行了盲法。2020 年 7 月 13 日至 2022 年 7 月 8 日期间，1656 名 PLHIV 接受了随机分组，每个研究组的人数相等。一名参与者被错误地第二次登记并在主要意向治疗分析中被排除。在其余 1655 名参与者中，接受并完成 3HP 的比例超过了 DOT（0.94；97.5%CI[0.91,0.96]p<0.001）、SAT（0.92；97.5%CI[0.89,0.94]p<0.001）和 Choice（0.93；97.5%CI[0.91,0.96]p<0.001）组的既定 80%目标。总体而言，在任何 2 个臂之间，或基于性别、抗逆转录病毒治疗时间、先前结核病或结核病感染治疗史的预设亚组分析中，接受和完成情况均无差异。只有 14 名（0.8%）参与者发生了导致停止 3HP 的不良事件。该研究的主要限制是它是在一个单一的中心进行的。现在需要进行多中心研究，以确认在其他环境中使用经过调整的促进 3HP 交付策略的可行性和普遍性。
乌干达的 PLHIV 广泛接受了短程结核病预防性治疗，并且在一个针对已知障碍量身定制交付策略的规划环境中，实现了非常高的治疗完成率。
ClinicalTrials.gov NCT03934931。
