Kadota Jillian L, Musinguzi Allan, Aschmann Hélène E, Akello Lydia, Welishe Fred, Nakimuli Jane, Berger Christopher A, Kiwanuka Noah, Phillips Patrick P J, Katamba Achilles, Dowdy David W, Cattamanchi Adithya, Semitala Fred C
Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, California, USA.
Center for Tuberculosis, University of California, San Francisco, San Francisco, California, USA.
Open Forum Infect Dis. 2024 Nov 14;11(11):ofae667. doi: 10.1093/ofid/ofae667. eCollection 2024 Nov.
Short-course tuberculosis (TB) prevention regimens, including 12 weeks of isoniazid and rifapentine (3HP), are increasingly used in high-TB-burden countries. Despite established safety and tolerability in efficacy trials, 3HP-related adverse events (AEs) could differ in routine settings. Real-world data on AE type, frequency, and timing are crucial for health systems considering 3HP programmatic scale-up.
We reviewed AEs among people with human immunodeficiency virus (HIV) participating in a pragmatic implementation trial of facilitated 3HP taken by directly observed therapy (DOT) or self-administered therapy (SAT) in Kampala, Uganda, and classified them using the Common Terminology Criteria for Adverse Events. We assessed AE timing and summarized related clinical actions including laboratory tests, diagnoses made, medications prescribed, and treatment interruptions.
Among 1655 people with HIV treated between July 2020 and September 2022, 270 (16.3%) reported 451 events; main issues included general (7%), nervous system (6%), musculoskeletal (5%), gastrointestinal (5%), and dermatologic (3%) disorders. Most (61%) occurred within 6 weeks of initiating 3HP. Among those with events, 211 (78%) required further clinician evaluation, 202 (75%) required laboratory testing, 102 (38%) had medications prescribed, 40 (15%) had treatment paused, and 14 (5%) discontinued 3HP. Women, those multidimensionally impoverished, and DOT recipients were more likely to report an AE. SAT users and later enrollees were more likely to have 3HP interrupted or stopped due to an AE.
In a routine setting, 3HP was safe, with 16% of people with HIV reporting AEs and only 3% requiring temporary or permanent treatment interruption. These findings support 3HP expansion in routine HIV/AIDS care settings for TB prevention. NCT03934931.
短程结核病（TB）预防方案，包括12周的异烟肼和利福喷汀（3HP），在高结核病负担国家越来越多地被使用。尽管在疗效试验中已确定了安全性和耐受性，但在常规环境中，与3HP相关的不良事件（AE）可能有所不同。对于考虑扩大3HP项目规模的卫生系统而言，关于AE类型、频率和时间的真实世界数据至关重要。
我们回顾了在乌干达坎帕拉参与一项务实实施试验的人类免疫缺陷病毒（HIV）感染者中的AE，该试验采用直接观察治疗（DOT）或自我给药治疗（SAT）方式服用简化的3HP，并使用不良事件通用术语标准对其进行分类。我们评估了AE发生时间，并总结了相关的临床行动，包括实验室检查、做出的诊断、开具的药物以及治疗中断情况。
在2020年7月至2022年9月期间接受治疗的1655名HIV感染者中，270人（16.3%）报告了451起事件；主要问题包括全身性（7%）、神经系统（6%）、肌肉骨骼系统（5%）、胃肠道（5%）和皮肤（3%）疾病。大多数（61%）发生在开始3HP治疗的6周内。在发生事件的患者中，211人（78%）需要进一步的临床医生评估，202人（75%）需要实验室检查，102人（38%）开具了药物，40人（15%）暂停了治疗，14人（5%）停用了3HP。女性、多维贫困者和接受DOT治疗者更有可能报告AE。SAT使用者和较晚入组者因AE更有可能导致3HP治疗中断或停止。
在常规环境中，3HP是安全的，16%的HIV感染者报告了AE，只有3%的人需要暂时或永久中断治疗。这些发现支持在常规HIV/AIDS护理环境中扩大3HP用于结核病预防。 NCT03934931。
