Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials.

OBJECTIVES To evaluate the efficacy of isoniazid for the prevention of tuberculosis in tuberculin skin test-positive and negative individuals with HIV infection. DESIGN Meta-analysis of randomized controlled trials. SETTING Seven trials from Mexico, Haiti, the United States, Zambia, Uganda and Kenya. PATIENTS Individuals free from tuberculosis, 2367 persons in the intervention and 2162 in the control groups. INTERVENTION Comparison of isoniazid with placebo or no prophylaxis. METHODS A systematic search of the literature was carried out from 1985 to October 1997 for randomized controlled trials of isoniazid prophylaxis in HIV-infected persons. Two reviewers evaluated the relevance of each candidate study and the validity of eligible trials. Studies were pooled using a random effect model, conducting secondary analyses for tuberculin skin test-positive and negative persons. RESULTS Mean follow-up in trials varied between 0.4 and 3.2 years. Pooling all seven trials, a risk ratio was found for persons treated with isoniazid for developing tuberculosis of 0.58 [95% confidence interval (CI), 0.43-0.80] and 0.94 (95% CI, 0.83-1.07) for death. In groups of tuberculin skin test-positive and negative persons, the risk ratio of tuberculosis was 0.40 (95% CI, 0.24-0.65) and 0.84 (95% CI, 0.54-1.30), respectively, and the difference in the effectiveness of isoniazid versus placebo between these groups was statistically significant (P = 0.03, for the difference of summary estimates). Consistency of results was found across trials (P > 0.10, heterogeneity value) for all comparisons. CONCLUSIONS Prophylaxis with isoniazid reduces the risk of tuberculosis in persons with HIV infection. The effect is restricted to tuberculin skin test-positive persons.