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 journalArticle

Abstract

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
JournalJournal of the American Medical Association
Volume283
Issue number11
StatePublished - Mar 15 2000
Externally publishedYes

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Pyrazinamide
Isoniazid
Rifampin
Tuberculosis
HIV
Multidrug-Resistant Tuberculosis
Pyridoxine
Tuberculin Test
Virus Diseases
Ambulatory Care Facilities
Mexico
Skin Tests
Brazil
Multivariate Analysis
Odds Ratio
Outcome Assessment (Health Care)
Confidence Intervals
Safety

ASJC Scopus subject areas

  • Medicine(all)

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Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons : An international randomized trial. / Gordin, Fred; Chaisson, Richard E; Matts, John P.; Miller, Carol; De Lourdes Garcia, Maria; Hafner, Richard; Valdespino, Jose Luis; Coberly, Jacqueline; Schechter, Mauro; Klukowicz, Alan J.; Barry, M. Anita; O'Brien, Richard J.

In: Journal of the American Medical Association, Vol. 283, No. 11, 15.03.2000, p. 1445-1450.

Research output: Contribution to journalArticle

Gordin, F, Chaisson, RE, Matts, JP, Miller, C, De Lourdes Garcia, M, Hafner, R, Valdespino, JL, Coberly, J, Schechter, M, Klukowicz, AJ, Barry, MA & O'Brien, RJ 2000, 'Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: An international randomized trial', Journal of the American Medical Association, vol. 283, no. 11, pp. 1445-1450.
Gordin, Fred ; Chaisson, Richard E ; Matts, John P. ; Miller, Carol ; De Lourdes Garcia, Maria ; Hafner, Richard ; Valdespino, Jose Luis ; Coberly, Jacqueline ; Schechter, Mauro ; Klukowicz, Alan J. ; Barry, M. Anita ; O'Brien, Richard J. / Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons : An international randomized trial. In: Journal of the American Medical Association. 2000 ; Vol. 283, No. 11. pp. 1445-1450.
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abstract = "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.",
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T1 - Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons

T2 - An international randomized trial

AU - Gordin, Fred

AU - Chaisson, Richard E

AU - Matts, John P.

AU - Miller, Carol

AU - De Lourdes Garcia, Maria

AU - Hafner, Richard

AU - Valdespino, Jose Luis

AU - Coberly, Jacqueline

AU - Schechter, Mauro

AU - Klukowicz, Alan J.

AU - Barry, M. Anita

AU - O'Brien, Richard J.

PY - 2000/3/15

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N2 - 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.

AB - 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.

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