A TRIAL OF 3 REGIMENS TO PREVENT TUBERCULOSIS IN UGANDAN ADULTS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS

Background Infection with the human immunodeficiency virus (HIV) great ly increases the risk of reactivation tuberculosis. We evaluated the s afety and efficacy of three preventive-therapy regimens in a setting w here exposure to tuberculosis is common. Methods We performed a random ized, placebo-controlled trial in 2736 HIV-infected adults recruited i n Kampala, Uganda. Subjects with positive tuberculin skin tests (indur ation, greater than or equal to 5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 su bjects), 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 i n reaction to PPD and candida antigens) were randomly assigned to rece ive either placebo (323 subjects) or six months of isoniazid (395). Th e medications were dispensed monthly and were self-administered. Resul ts Among the PPD-positive subjects, the incidence of tuberculosis in t he three groups that received preventive therapy was lower than the ra te 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 isoniazi d 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, th e relative risk of tuberculosis was 0.83 (95 percent confidence interv al, 0.34 to 2.04) with isoniazid as compared with placebo. Side effect s 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 isoniazi d confers short-term protection against tuberculosis among PPD-positiv e, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis. (C) 1997 , Massachusetts Medical Society.