The impact of isoniazid preventive therapy and antiretroviral therapy on tuberculosis in children infected with HIV in a high tuberculosis incidence setting
Background: Tuberculosis (TB) is a major cause of morbidity and mortality among children infected with HIV. Strategies to prevent TB in children include isoniazid preventive therapy (IPT) and antiretroviral therapy (ART). IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children. Objective: To investigate the combined effect of IPT and ART on TB risk in children infected with HIV. Methods: A cohort analysis was done within a prospective, double-blinded, placebo-controlled trial of isoniazid (INH) compared with placebo in children infected with HIV in Cape Town, South Africa, a high TB incidence setting. In May 2004 the placebo arm was terminated and all children were switched to INH. ART was not widely available at the start of the study, but children were started on ART following the establishment of the national ART program in 2004. Data were analysed using Cox proportional hazard regression. Results: After adjusting for age, nutritional status and immunodeficiency at enrolment, INH alone, ART alone and INH combined with ART reduced the risk of TB disease by 0.22 (95% CI 0.09 to 0.53), 0.32 (95% CI 0.07 to 1.55) and 0.11 (95% CI 0.04 to 0.32) respectively. INH reduced the risk of TB disease in children on ART by 0.23 (95% CI 0.05 to 1.00). Conclusions: The finding that IPT may offer additional protection in children on ART has significant public health implications because this offers a possible strategy for reducing TB in children infected with HIV. Widespread use of this strategy will however require screening of children for active TB disease. Trial registration: Trial registration - Clinical Trials NCT00330304.