title: Impact of tuberculosis preventive therapy on tuberculosis and mortality in HIV-infected children.
abstract: BACKGROUND
  Children with HIV are at increased risk of acquiring tuberculosis (TB), a common cause of acute and chronic respiratory disease and death in HIV-infected children living in areas where prevalence of the disease is high. Children infected with HIV and TB have worse outcomes than HIV-uninfected children who have TB; thus, preventing the infection and disease in HIV-infected children is potentially an important public health intervention. Isoniazid, an anti-tuberculosis medication, has been used effectively to prevent TB in HIV-uninfected children, but currently there are no guidelines on the use of TB preventive therapy in HIV-infected children.
  
  
  OBJECTIVE
  To determine the impact of TB preventive therapy on TB-related incidence and death in HIV-infected children
  
  
  METHODS
  We searched the Cochrane Controlled Trials Register (CENTRAL/CCTR), Cochrane HIV/AIDS Group Specialized Register, MEDLINE/PubMed, EMBASE, and AIDSearch. In addition, we scanned reference lists, manually searched conference abstracts, and contacted content experts.
  
  
  METHODS
  We included studies of HIV-infected children randomised to receive TB preventive therapy or placebo, or an alternative TB preventive regimen. Participants could have tuberculin skin test results that were positive or negative.
  
  
  METHODS
  Two authors independently used the study selection criteria, assessed methodological quality and extracted data. Effects were assessed using hazard ratios.
  
  
  RESULTS
  One trial met the selection criteria for the review. The trial participants were HIV-infected children, most of whom were not taking antiretroviral therapy. Subjects were randomised to isoniazid and cotrimoxazole or placebo and cotrimoxazole, given daily or three times a week. The trial showed a marked reduction in TB incidence and death in the isoniazid group. As yet, however, there are no long-term follow-up data on the durability of the protective effect or on possible long-term adverse events. This trial also was unable to assess the impact of isoniazid prophylaxis on children receiving antiretroviral therapy.
  
  
  CONCLUSIONS
  Isoniazid prophylaxis in HIV-infected children has the potential to play a major public health role by reducing TB incidence and death. As yet, however, data are insufficient to guide the duration of prophylaxis and to support its use in children using highly active antiretroviral therapy (HAART) and in those living in areas of low TB prevalence. Further studies are needed to assess whether TB preventive therapy is of benefit in all HIV-infected children, irrespective of use of antiretroviral treatment, the optimal duration of preventive therapy, or long-term adverse events.
authors.affiliation: G25 HIV/AIDS Paediatric Service, Groote Schuur Hospital, Cape Town, Western Cape, South Africa, 7700. dgray@ich.uct.ac.za
authors.forename: Diane M
authors.initials: DM
authors.lastname: Gray
authors.forename: Heather
authors.initials: H
authors.lastname: Zar
authors.forename: Mark
authors.initials: M
authors.lastname: Cotton
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000401:mortality / Q000517:prevention & control; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000401:mortality* / Q000517:prevention & control*
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D007538:Isoniazid