EFFECT OF PREVENTIVE TREATMENT FOR TUBERCULOSIS IN ADULTS INFECTED WITH HIV - SYSTEMATIC REVIEW OF RANDOMIZED PLACEBO-CONTROLLED TRIALS

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 ran domised placebo controlled trials. Main outcome measures: Active tuber culosis, mortality, and adverse drug reaction requiring cessation of t he study regimen. Outcomes stratified by status of purified protein de rivative skin test Results: Four trials comprising 4055 adults from Ha iti, Kenya, the United States, and Uganda were included. All compared isoniazid (6-12 months) with placebo, and one trial also compared mult idrug treatment for 3 months with placebo. Mean follow up was 15-33 mo nths. Overall, frequency of tuberculosis (relative risk 0.57, 95% conf idence interval 0.41 to 0.79) was reduced in those receiving preventiv e. treatment compared with placebo: mortality was not significantly re duced (0.93, 0.83 to 1.05), In subjects positive for purified protein derivative receiving preventive treatment, the risk of tuberculosis wa s 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 pl acebo. In adults negative for purified protein derivative receiving pr eventive 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 agai nst 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 be nefits remain to be shown.