title: Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial.
abstract: OBJECTIVE
  To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV.
  
  
  METHODS
  Two centre prospective double blind placebo controlled trial.
  
  
  METHODS
  Children aged > or =8 weeks with HIV.
  
  
  METHODS
  Isoniazid or placebo given with co-trimoxazole either daily or three times a week.
  
  
  METHODS
  Two tertiary healthcare centres in South Africa.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  Clinical Trials NCT00330304.
authors.affiliation: School of Child and Adolescent Health, Red Cross Children's Hospital, University of Cape Town, South Africa. hzar@ich.uct.ac.za
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Zar
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.forename: Stanzi
authors.initials: S
authors.lastname: Strauss
authors.forename: Janine
authors.initials: J
authors.lastname: Karpakis
authors.forename: Gregory
authors.initials: G
authors.lastname: Hussey
authors.forename: H Simon
authors.initials: HS
authors.lastname: Schaaf
authors.forename: Helena
authors.initials: H
authors.lastname: Rabie
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Lombard
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003906:Developing Countries; D004311:Double-Blind Method; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D006297:Health Services Accessibility; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007538:Isoniazid / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000401:mortality
chemical_list: D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents; D007538:Isoniazid