CONTEXT: Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed. OBJECTIVE: To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection. DESIGN: Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997. SETTING: Outpatient clinics in the United States, Mexico, Haiti, and Brazil. PARTICIPANTS: A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result. INTERVENTIONS: Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791). MAIN OUTCOME MEASURES: The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group. RESULTS: Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P = .28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01). Neither regimen appeared to lead to the development of drug-resistant tuberculosis. CONCLUSIONS: Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs.
RCT Entities:
CONTEXT: Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed. OBJECTIVE: To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection. DESIGN: Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997. SETTING:Outpatient clinics in the United States, Mexico, Haiti, and Brazil. PARTICIPANTS: A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result. INTERVENTIONS:Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791). MAIN OUTCOME MEASURES: The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group. RESULTS: Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P = .28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01). Neither regimen appeared to lead to the development of drug-resistant tuberculosis. CONCLUSIONS: Our data suggest that for preventing tuberculosis in HIV-infectedpatients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs.
Authors: Marcus V N de Souza; Camilo H da Silva Lima; James L Wardell; Solange M S V Wardell; Edward R T Tiekink Journal: Acta Crystallogr Sect E Struct Rep Online Date: 2011-06-18
Authors: P Sadaphal; J Astemborski; N M Graham; L Sheely; M Bonds; A Madison; D Vlahov; D L Thomas; T R Sterling Journal: Clin Infect Dis Date: 2001-10-12 Impact factor: 9.079
Authors: Eric Nuermberger; Sandeep Tyagi; Kathy N Williams; Ian Rosenthal; William R Bishai; Jacques H Grosset Journal: Am J Respir Crit Care Med Date: 2005-09-08 Impact factor: 21.405