Factors predictive of early discontinuation of preventive treatment in children with household exposure to multidrug-resistant tuberculosis

Background The World Health Organization recommended levofloxacin for tuberculosis (TB) preventive treatment for child and adult contacts of multidrug-resistant (MDR)-TB. Method TB-CHAMP (ISRCTN92634082) was a double-blind community-based multi-site randomised placebo-controlled trial assessing levofloxacin as preventive treatment in children with household exposure to adults with microbiologically-confirmed MDR-TB in South Africa. Households were randomised 1:1 to 24-weeks daily levofloxacin (adult scored 250mg tablets) versus placebo. Treatment adherence was ascertained through pill counts and treatment cards. Competing risk methods were used to assess factors associated with early treatment discontinuation for non-clinical reasons before achieving ≥80% of allocated doses (adequate treatment). Results Among 911 of 922 children included in analysis, 90% were below 5 years of age. Overall, 765 (84%) of children achieved adequate treatment, 135 (15%) discontinued treatment early, and 11 (1%) had not achieved adequate treatment by the end-of-treatment period. Sixty-four (7%) children stopped for clinical reasons and 71 (8%) for non-clinical reasons, with similar proportions across treatment groups. Baseline factors associated with early treatment discontinuation for non-clinical reasons were previous receipt of herbal/traditional medicine (subhazard ratio 3.08, 95% CI 1.69-5.59, P<0.001), and caregivers reporting difficulties administering medication (subhazard ratio 2.73, 1.11-6.71, P=0.029). Children with poor treatment adherence by week 4 were more likely to subsequently stop treatment early for non-clinical reasons (subhazard ratio 2.72, 1.06-6.97, P=0.037). Conclusions Adherence to the 250mg levofloxacin formulation was good among young children on tuberculosis preventive therapy. Adherence support for children and caregivers, and addressing early signs of poor adherence, may enhance treatment completion.