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Preventive therapy for tuberculosis in HIV infection.

Objective To determine whether preventive treatment for
 tuberculosis in adults infected with HIV reduces the frequency of
 tuberculosis and overall mortality.
 Design Systematic review and data synthesis of randomised placebo
 controlled trials.
 Main Outcome Measures 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).
 ConclusionsPreventive 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.