Isoniazid for preventing tuberculosis in non‐HIV infected persons

BACKGROUND: Although isoniazid (INH) is commonly used for treating tuberculosis (TB), it is also effective as preventive therapy. OBJECTIVES: The objective of this review was to estimate the effect of 6 and 12 month courses of INH for preventing TB in HIV-negative people at increased risk of developing active TB. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We hand-searched Science Citation Index and Index Medicus. SELECTION CRITERIA: Randomised trials of INH preventive therapy for 6 months or more compared with placebo. Follow-up for a minimum of 2 years. Trials enrolling patients with current or previously treated active TB, or with known HIV infection, were excluded. Criteria were applied by two reviewers independently. DATA COLLECTION AND ANALYSIS: Trial quality was assessed by two reviewers independently, and data extracted by one reviewer using a standardized extraction form. MAIN RESULTS: Eleven trials involving 73,375 patients were included. Trials were generally of high quality. Treatment with INH resulted in a relative risk (RR) of developing active TB of 0.40, (95% confidence interval ¿CI¿ 0.31 to 0.52), over two years or longer. There was no significant difference between 6 and 12 month courses (RR of 0.44, 95% CI 0.27 to 0.73 for six months, and 0.38, 95% CI 0.28 to 0.50 for 12 months). Preventive therapy reduced deaths from TB, but this effect was not seen for all cause mortality. INH was associated with hepatotoxicity in 0.36% of people on 6 months treatment and in 0.52% of people treated for 12 months. REVIEWER'S CONCLUSIONS: Isoniazid is effective for the prevention of active TB in diverse at-risk patients, and six and 12 month regimens have a similar effect.