OBJECTIVES: To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV. DESIGN: Two centre prospective double blind placebo controlled trial. PARTICIPANTS: Children aged > or =8 weeks with HIV. INTERVENTIONS:Isoniazid or placebo given with co-trimoxazole either daily or three times a week. SETTING:Two tertiary healthcare centres in South Africa. MAIN OUTCOME MEASURES: Mortality, incidence of tuberculosis, and adverse events. RESULTS: Data on 263 children (median age 24.7 months) were available when the data safety monitoring board recommended discontinuing the placebo arm; 132 (50%) were taking isoniazid. Median follow-up was 5.7 (interquartile range 2.0-9.7) months. Mortality was lower in the isoniazid group than in the placebo group (11 (8%) v 21 (16%), hazard ratio 0.46, 95% confidence interval 0.22 to 0.95, P=0.015) by intention to treat analysis. The benefit applied across Centers for Disease Control clinical categories and in all ages. The reduction in mortality was similar in children on three times a week or daily isoniazid. The incidence of tuberculosis was lower in the isoniazid group (5 cases, 3.8%) than in the placebo group (13 cases, 9.9%) (hazard ratio 0.28, 0.10 to 0.78, P=0.005). All cases of tuberculosis confirmed by culture were in children in the placebo group. CONCLUSIONS: Prophylaxis with isoniazid has an early survival benefit and reduces incidence of tuberculosis in children with HIV. Prophylaxis may offer an effective public health intervention to reduce mortality in such children in settings with a high prevalence of tuberculosis. TRIAL REGISTRATION: Clinical Trials NCT00330304.
RCT Entities:
OBJECTIVES: To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV. DESIGN: Two centre prospective double blind placebo controlled trial. PARTICIPANTS: Children aged > or =8 weeks with HIV. INTERVENTIONS:Isoniazid or placebo given with co-trimoxazole either daily or three times a week. SETTING: Two tertiary healthcare centres in South Africa. MAIN OUTCOME MEASURES: Mortality, incidence of tuberculosis, and adverse events. RESULTS: Data on 263 children (median age 24.7 months) were available when the data safety monitoring board recommended discontinuing the placebo arm; 132 (50%) were taking isoniazid. Median follow-up was 5.7 (interquartile range 2.0-9.7) months. Mortality was lower in the isoniazid group than in the placebo group (11 (8%) v 21 (16%), hazard ratio 0.46, 95% confidence interval 0.22 to 0.95, P=0.015) by intention to treat analysis. The benefit applied across Centers for Disease Control clinical categories and in all ages. The reduction in mortality was similar in children on three times a week or daily isoniazid. The incidence of tuberculosis was lower in the isoniazid group (5 cases, 3.8%) than in the placebo group (13 cases, 9.9%) (hazard ratio 0.28, 0.10 to 0.78, P=0.005). All cases of tuberculosis confirmed by culture were in children in the placebo group. CONCLUSIONS: Prophylaxis with isoniazid has an early survival benefit and reduces incidence of tuberculosis in children with HIV. Prophylaxis may offer an effective public health intervention to reduce mortality in such children in settings with a high prevalence of tuberculosis. TRIAL REGISTRATION: Clinical Trials NCT00330304.
Authors: A C Hesseling; A E Westra; H Werschkull; P R Donald; N Beyers; G D Hussey; W El-Sadr; H Simon Schaaf Journal: Arch Dis Child Date: 2005-06-17 Impact factor: 3.791
Authors: H J Zar; D Hanslo; E Tannenbaum; M Klein; A Argent; B Eley; J Burgess; K Magnus; E D Bateman; G Hussey Journal: Acta Paediatr Date: 2001-02 Impact factor: 2.299
Authors: C Chintu; G J Bhat; A S Walker; V Mulenga; F Sinyinza; K Lishimpi; L Farrelly; N Kaganson; A Zumla; S H Gillespie; A J Nunn; D M Gibb Journal: Lancet Date: 2004 Nov 20-26 Impact factor: 79.321
Authors: Katalin A Wilkinson; Onn M Kon; Sandra M Newton; Graeme Meintjes; Robert N Davidson; Geoffrey Pasvol; Robert J Wilkinson Journal: J Infect Dis Date: 2005-12-29 Impact factor: 5.226
Authors: L L Abuogi; C Mwachari; H H Leslie; S B Shade; J Otieno; N Yienya; L Sanguli; E Amukoye; C R Cohen Journal: Int J Tuberc Lung Dis Date: 2013-10 Impact factor: 2.373
Authors: Jason R Andrews; Elisa Nemes; Michele Tameris; Bernard S Landry; Hassan Mahomed; J Bruce McClain; Helen A Fletcher; Willem A Hanekom; Robin Wood; Helen McShane; Thomas J Scriba; Mark Hatherill Journal: Lancet Respir Med Date: 2017-02-16 Impact factor: 30.700
Authors: Nazma Mansoor; Thomas J Scriba; Marwou de Kock; Michele Tameris; Brian Abel; Alana Keyser; Francesca Little; Andreia Soares; Sebastian Gelderbloem; Silvia Mlenjeni; Lea Denation; Anthony Hawkridge; W Henry Boom; Gilla Kaplan; Gregory D Hussey; Willem A Hanekom Journal: J Infect Dis Date: 2009-04-01 Impact factor: 5.226
Authors: Stanzi M le Roux; Mark F Cotton; Jonathan E Golub; David M le Roux; Lesley Workman; Heather J Zar Journal: BMC Med Date: 2009-11-03 Impact factor: 8.775
Authors: Cécile Alexandra Peltier; Christine Omes; Patrick Cyaga Ndimubanzi; Gilles François Ndayisaba; Sara Stulac; Vic Arendt; Olivier Courteille; Narcisse Muganga; Kizito Kayumba; Jef Van den Ende Journal: PLoS One Date: 2009-04-24 Impact factor: 3.240