Effect of preventive treatment for tuberculosis in adults infected with HIV: systematic review of randomised placebo controlled trials.
OBJECTIVE
To determine whether preventive treatment for tuberculosis in adults infected with HIV reduces the frequency of tuberculosis and overall mortality.


METHODS
Systematic review and data synthesis of randomised placebo controlled trials.


METHODS
Active tuberculosis, mortality, and adverse drug reaction requiring cessation of the study regimen. Outcomes stratified by status of purified protein derivative skin test.


RESULTS
Four trials comprising 4055 adults from Haiti, Kenya, the United States, and Uganda were included. All compared isoniazid (6-12 months) with placebo, and one trial also compared multidrug treatment for 3 months with placebo. Mean follow up was 15-33 months. Overall, frequency of tuberculosis (relative risk 0.57, 95% confidence interval 0.41 to 0.79) was reduced in those receiving preventive treatment compared with placebo: mortality was not significantly reduced (0.93, 0.83 to 1.05). In subjects positive for purified protein derivative receiving preventive treatment, the risk of tuberculosis was reduced substantially (0.32, 0.19 to 0.51) and the risk of death was reduced moderately (0.73, 0.57 to 0.95) compared with those taking placebo. In adults negative for purified protein derivative receiving preventive treatment, the risk of tuberculosis (0.82, 0.50 to 1.36) and the risk of death (1.02, 0.89 to 1.17) were not reduced significantly. Adverse drug reactions were more frequent, but not significantly so, in patients receiving drug compared with placebo (1.45, 0.98 to 2.14).


CONCLUSIONS
Preventive treatment given for 3-12 months protects against tuberculosis in adults infected with HIV, at least in the short to medium term. Protection is greatest in subjects positive for purified protein derivative, in whom death is also less frequent. Long term benefits remain to be shown.
Wilkinson
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Centre for Epidemiological Research in Southern Africa, Medical Research Council, PO Box 187, Mtubatuba 3935, South Africa. wilkinsd@mrc.ac.za
Squire
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SB
Garner
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D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014374:Tuberculin Test; D014376:Tuberculosis / Q000150:complications / Q000517:prevention & control*
D000995:Antitubercular Agents; D007538:Isoniazid