title: Treatment of latent tuberculosis infection in HIV infected persons.
abstract: BACKGROUND
  Individuals with human immunodeficiency virus (HIV) infection are at an increased risk of developing active tuberculosis (TB). It is known that treatment of latent TB infection (LTBI), also referred to as TB preventive therapy or chemoprophylaxis, helps to prevent progression to active disease in HIV negative populations. However, the extent and magnitude of protection (if any) associated with preventive therapy in those infected with HIV should be quantified. This present study is an update of the original review.
  
  
  OBJECTIVE
  To determine the effectiveness of TB preventive therapy in reducing the risk of active tuberculosis and death in HIV-infected persons.
  
  
  METHODS
  This review was updated using the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, AIDSLINE, AIDSTRIALS, AIDSearch, NLM Gateway and AIDSDRUGS (publication date from 01 July 2002 to 04 April 2008). We also scanned reference lists of articles and contacted authors and other researchers in the field in an attempt to identify additional studies that may be eligible for inclusion in this review.
  
  
  METHODS
  We included randomized controlled trials in which HIV positive individuals were randomly allocated to TB preventive therapy or placebo, or to alternative TB preventive therapy regimens. Participants could be tuberculin skin test positive or negative, but without active tuberculosis.
  
  
  METHODS
  Three reviewers independently applied the study selection criteria, assessed study quality and extracted data. Effects were assessed using relative risk for dichotomous data and mean differences for continuous data.
  
  
  RESULTS
  12 trials were included with a total of 8578 randomized participants. TB preventive therapy (any anti-TB drug) versus placebo was associated with a lower incidence of active TB (RR 0.68, 95% CI 0.54 to 0.85). This benefit was more pronounced in individuals with a positive tuberculin skin test (RR 0.38, 95% CI 0.25 to 0.57) than in those who had a negative test (RR 0.89, 95% CI 0.64 to 1.24). Efficacy was similar for all regimens (regardless of drug type, frequency or duration of treatment). However, compared to INH monotherapy, short-course multi-drug regimens were much more likely to require discontinuation of treatment due to adverse effects. Although there was reduction in mortality with INH monotherapy versus placebo among individuals with a positive tuberculin skin test (RR 0.74, 95% CI 0.55 to 1.00) and with INH plus rifampicin versus placebo regardless of tuberculin skin test status (RR 0.69, 95% CI 0.50 to 0.95), overall, there was no evidence that TB preventive therapy versus placebo reduced all-cause mortality (RR 0.94, 95% CI 0.85 to 1.05).
  
  
  CONCLUSIONS
  Treatment of latent tuberculosis infection reduces the risk of active TB in HIV positive individuals especially in those with a positive tuberculin skin test. The choice of regimen will depend on factors such as availability, cost, adverse effects, adherence and drug resistance. Future studies should assess these aspects. In addition, trials evaluating the long-term effects of anti-tuberculosis chemoprophylaxis, the optimal duration of TB preventive therapy, the influence of level of immunocompromise on effectiveness and combination of anti-tuberculosis chemoprophylaxis with antiretroviral therapy are needed.
authors.affiliation: Department of Public Health, University of Oxford, Oxford, UK, OX3 7LF.
authors.forename: Christopher
authors.initials: C
authors.lastname: Akolo
authors.forename: Ifedayo
authors.initials: I
authors.lastname: Adetifa
authors.forename: Sasha
authors.initials: S
authors.lastname: Shepperd
authors.forename: Jimmy
authors.initials: J
authors.lastname: Volmink
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D055985:Latent Tuberculosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid