Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group.
BACKGROUND
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.


METHODS
Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997.


METHODS
Outpatient clinics in the United States, Mexico, Haiti, and Brazil.


METHODS
A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result.


METHODS
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).


METHODS
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.
Gordin
F
F
Veterans Affairs Medical Center and Georgetown University, Washington, DC 20422, USA. vawrap@erols.com
Chaisson
R E
RE
Matts
J P
JP
Miller
C
C
de Lourdes Garcia
M
M
Hafner
R
R
Valdespino
J L
JL
Coberly
J
J
Schechter
M
M
Klukowicz
A J
AJ
Barry
M A
MA
O'Brien
R J
RJ
D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000401:mortality / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000382:microbiology* / Q000401:mortality; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D016016:Proportional Hazards Models; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000401:mortality / Q000517:prevention & control*
D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin