Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: An international randomized trial

Fred Gordin, Richard E. Chaisson, John P. Matts, Carol Miller, Maria De Lourdes Garcia, Richard Hafner, Jose Luis Valdespino, Jacqueline Coberly, Mauro Schechter, Alan J. Klukowicz, M. Anita Barry, Richard J. O'Brien

Research output: Contribution to journalArticlepeer-review

267 Scopus citations


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, Hafti, 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.

Original languageEnglish (US)
Pages (from-to)1445-1450
Number of pages6
Issue number11
StatePublished - Mar 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: An international randomized trial'. Together they form a unique fingerprint.

Cite this