Adverse Events Reported During Weekly Isoniazid-Rifapentine (3HP) Tuberculosis Preventive Treatment Among People With Human Immunodeficiency Virus in Uganda

• Published in: Open forum infectious diseases 2024-11, Vol.11 (11), p.ofae667
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Global Health and Infectious Diseases
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofae667

Abstract Background 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. Methods 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. Results 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. Conclusions 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. Clinical Trials Registration. NCT03934931. Weekly isoniazid and rifapentine is being rolled out for tuberculosis prevention in high-burden countries. We describe the incidence and clinical management of adverse events in a real-world clinical setting among people with HIV participating in a pragmatic implementation study in Uganda.