title: Safety of long-term isoniazid preventive therapy in children with HIV: a comparison of two dosing schedules.
abstract: METHODS
  Two paediatric hospitals in Cape Town, South Africa.
  
  
  OBJECTIVE
  To investigate the incidence of and risk factors for severe liver injury in human immunodeficiency virus (HIV) infected children receiving long-term isoniazid preventive therapy (IPT).
  
  
  METHODS
  Randomised  trial of IPT or placebo given daily or thrice weekly to HIV-infected children aged ≥8 weeks; placebo was discontinued early. Alanine transaminase (ALT) was measured at baseline, 6-monthly and during illness: an increase of ≥10 times the upper limit of normal defined severe liver injury.
  
  
  RESULTS
  Of 324 children enrolled, 297 (91.6%) received IPT (559.1 person-years [py]). Baseline median age was 23 months (interquartile range [IQR] 9.5-48.6) and median CD4%, 20% (IQR 13.6-26.9). A total of 207 (63.9%) children received combination antiretroviral therapy: 19 developed severe  liver injury, 16 while receiving IPT. Among these there were 8 cases of viral hepatitis (5 with hepatitis A), 2 antiretroviral-induced liver injuries and 1 case of abdominal tuberculosis. IPT-related severe liver injury occurred in 1.7% (5/297, 0.78/100 py). No child developed hepatic failure;  one died of an unrelated cause. All surviving children subsequently tolerated IPT.
  
  
  CONCLUSIONS
  This study suggests that long-term IPT has a low toxicity risk in HIV-infected children. In the absence of chronic viral hepatitis, IPT can be safely re-introduced following recovery from liver  injury.
authors.affiliation: Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa. stanzi.leroux@gmail.com
authors.forename: S M
authors.initials: SM
authors.lastname: le Roux
authors.forename: M F
authors.initials: MF
authors.lastname: Cotton
authors.forename: L
authors.initials: L
authors.lastname: Myer
authors.forename: D M
authors.initials: DM
authors.lastname: le Roux
authors.forename: H S
authors.initials: HS
authors.lastname: Schaaf
authors.forename: C J
authors.initials: CJ
authors.lastname: Lombard
authors.forename: H J
authors.initials: HJ
authors.lastname: Zar
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D015994:Incidence; D007223:Infant; D007538:Isoniazid / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014376:Tuberculosis / Q000209:etiology* / Q000517:prevention & control*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid