title: Three months of rifapentine and isoniazid for latent tuberculosis infection.
abstract: BACKGROUND
  Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion.
  
  
  METHODS
  We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%.
  
  
  RESULTS
  In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P=0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001).
  
  
  CONCLUSIONS
  The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.).
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN, USA. timothy.sterling@vanderbilt.edu
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sterling
authors.forename: M Elsa
authors.initials: ME
authors.lastname: Villarino
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Borisov
authors.forename: Nong
authors.initials: N
authors.lastname: Shang
authors.forename: Fred
authors.initials: F
authors.lastname: Gordin
authors.forename: Erin
authors.initials: E
authors.lastname: Bliven-Sizemore
authors.forename: Judith
authors.initials: J
authors.lastname: Hackman
authors.forename: Carol Dukes
authors.initials: CD
authors.lastname: Hamilton
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
authors.forename: Amy
authors.initials: A
authors.lastname: Kerrigan
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Weis
authors.forename: Marc
authors.initials: M
authors.lastname: Weiner
authors.forename: Diane
authors.initials: D
authors.lastname: Wing
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Conde
authors.forename: Lorna
authors.initials: L
authors.lastname: Bozeman
authors.forename: C Robert
authors.initials: CR
authors.lastname: Horsburgh
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023801:Directly Observed Therapy; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D057194:Intention to Treat Analysis; D007538:Isoniazid / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D012307:Risk Factors; D012646:Self Administration; D014376:Tuberculosis / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D017735:Virus Latency
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine