Completion, Safety and Tolerability of Once-weekly Isoniazid and Rifapentine for Tuberculosis Infection by Children and Adolescents

BACKGROUND: Treating patients for tuberculosis (TB) infection prevents future cases and transmission. Long treatment regimens have been associated with low completion rates. We describe a 1-decade experience with treating children and adolescents for TB infection (TBI) with 3 months of once-weekly doses of isoniazid and rifapentine (3HP). METHODS: This was a retrospective review (2014-2024) of 2 to <21 year olds who received 3HP under directly observed therapy for TBI. We abstracted demographic data, testing methods and treatment course information. Our primary outcome was treatment completion; our secondary outcome was adverse events (AEs). RESULTS: Eight hundred two patients met inclusion criteria; 94.1% completed therapy. Completion rates were not associated with demographic data or testing methods. The most common reasons for not completing 3HP were AEs (23/802, 3%), moving out of the area (11, 1.4%) and pill burden (7, 0.9%). AEs resulting in failure to complete 3HP were rare. These included vomiting (15; 2 with elevated aspartate aminotransferase/alanine aminotransferase), abdominal pain (7, all with normal aspartate aminotransferase/alanine aminotransferase), rash (6), angioedema (4) and myalgias (2); 16/23 had >1 AE. Of the 23 with AEs, 20 began alternative regimens [rifampin (12), levofloxacin (5) and isoniazid (3)], and 17/20 (85%) completed TBI therapy. CONCLUSIONS: Over 94% of children as young as 2 years of age completed 3HP for TBI, which is remarkable considering the large pill burden and lack of child-friendly formulations available in the United States. The only factor associated with treatment completion was the presence of an AE.