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Volume 337:801-808 September 18, 1997 Number 12 Next

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ABSTRACT

Background Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common.

Methods We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, >5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered.

Results Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P = 0.002 by the log-rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD-positive subjects.

Conclusions A six-month course of isoniazid confers short-term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis.

Source Information

From the Division of Infectious Diseases, Department of Medicine, University Hospitals of Cleveland and Case Western Reserve University (C.C.W., J.L.J., D.L.H., J.J.E.), and the Department of Epidemiology and Biostatistics, Case Western Reserve University (C.C.W.) — all in Cleveland; the Ugandan Ministry of Health, National Tuberculosis and Leprosy Programme (A.O.), the Joint Clinical Research Center (P.M.), and Makerere University (R.D.M.) — all in Kampala, Uganda; and the Centers for Disease Control and Prevention, Atlanta (R.H.). Other authors were Peter Nsubuga, M.B., Ch.B., Ministry of Health, Kampala; Michael Vjecha, M.D., University Hospitals of Cleveland and Case Western Reserve University, Cleveland; Harriet Myanja, M.B., Ch.B., M.Med, Makerere University, Kampala; Cissy Kityo, M.B., Ch.B., Joint Clinical Research Center, Kampala; and Anita Loughlin, M.S., John Milberg, M.P.H., and Vukosava Pekovic, M.D., Ph.D., all of University Hospitals of Cleveland and Case Western Reserve University, Cleveland.

Address reprint requests to Dr. Whalen at the Dept. of Epidemiology and Biostatistics, WG-49, Case Western Reserve University, 10900 Euclid Blvd., Cleveland, OH 44106-4945.

Full Text of this Article

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Questions about a Placebo-Controlled Trial of Preventive Therapy for Tuberculosis in HIV-Infected Ugandans
Desvarieux M., Turner M. T., Whalen C. C., Johnson J. L., Mugerwa R. D., Ellner J. J., Msamanga G., Angell M.
Extract | Full Text  
N Engl J Med 1998; 338:841-843, Mar 19, 1998. Correspondence

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