Safety and feasibility of 1 month of daily rifapentine plus isoniazid to prevent tuberculosis in children and adolescents: a prospective cohort study.

BACKGROUND: Shorter regimens for tuberculosis prevention can improve completion rates and protection against developing active tuberculosis disease after tuberculosis exposure. We aimed to assess the safety and feasibility of 1 month of daily isoniazid and rifapentine (1HP) in children and adolescents in a low-resource setting in south Asia with low prevalence of HIV. METHODS: This prospective cohort study was done in eight tuberculosis facilities in Karachi, Pakistan. Eligible participants were aged 2-19 years and were household contacts of patients with drug-susceptible tuberculosis infection. After clinical, radiological, and laboratory evaluation to rule out tuberculosis disease, participants were prescribed 1HP as a preventive regimen. Isoniazid was administered as 100 mg or 300 mg oral tablets and rifapentine was administered as 150 mg oral tablets. Dosing was according to participant bodyweight. The primary endpoints were the cumulative probability of a household contact completing all stages of the preventive care cascade, assessed in all eligible participants, and the proportion of household contacts completing 1HP, assessed among all those who initiated the regimen. Safety was assessed in all household contacts who initiated the 1HP regimen. FINDINGS: Between Dec 21, 2019, and March 20, 2020, 1395 household contacts of 253 patients with tuberculosis were identified, including 678 household contacts who were eligible to participate. 628 (93%) completed evaluation, of whom ten (2%) had active tuberculosis disease. Of the 618 individuals eligible for tuberculosis prevention, 408 (66%) initiated 1HP, 385 (94%) of whom completed the regimen. The median duration of 1HP was 31 days (IQR 30-32) in those who completed the regimen. The cumulative probability of completing all steps of the tuberculosis prevention cascade was 58%. A girl aged 11 years developed tuberculosis disease within 6 months of completing 1HP. A boy aged 14 years developed a burning sensation during 1HP therapy and discontinued the regimen. No other adverse events were observed. INTERPRETATION: 1HP can be safely and feasibly implemented as tuberculosis prevention in children and adolescents in programmatic settings. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria.