The impact of isoniazid preventive therapy and antiretroviral therapy on tuberculosis in children infected with HIV in a high tuberculosis incidence setting
- 1Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, Cape Town, South Africa
- 2Clinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
- 3Department of Paediatrics and Child Health, Stellenbosch University, South Africa
- 4Biostatistics Unit, Medical Research Council, Cape Town, South Africa
- Correspondence to Dr L J Frigati, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, Klipfontein Road, Rondebosch 7700, South Africa;
- Received 27 November 2010
- Accepted 17 February 2011
- Published Online First 2 April 2011
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.
The data and safety monitoring board comprised J Kaplan (chair), W El Sadr, P Donald and N Beyers.
Funding Funding for the study was from Rockefeller Foundation, USA; Medical Research Council, South Africa and Department of Health, South Africa. All authors have completed the Unified Competing Interest form and declare financial support from Rockefeller Foundation, USA and Medical Research Council, South Africa and Department of Health, South Africa. All authors also declare no financial relationships with commercial entities that might have an interest in the submitted work; no spouses, partners or children with relationships with commercial entities that might have an interest in the submitted work; no non-financial interests that may be relevant to the submitted work.
Competing interests None.
Ethics approval This study was conducted with the approval of the ethics committees of the Faculty of Health Sciences, University of Cape Town and of Stellenbosch University.
Provenance and peer review Not commissioned; externally peer reviewed.