title: Tackling the unknowns of short-course rifapentine-based treatment for active tuberculosis: a decision analysis.
abstract: Shorter treatment regimens for tuberculosis (TB) are deemed vital for advancing TB control. Murine studies have suggested potential new regimens; however, Phase II human studies of these drug combinations have not shown clear improvement in 2-month culture conversion over current therapy. Nevertheless, drugs such as rifapentine (RPT) may have additional sterilizing effects after 2 months that are difficult to measure in current Phase II studies.
  
  
  
  To model potential bactericidal effects of RPT in a Phase III trial of a 4-month anti-tuberculosis regimen.
  
  
  
  We developed a Markov model of anti-tuberculosis treatment to compare two regimens for treating TB: a 6-month standard (rifampin-based) treatment and a 4-month regimen using high-dose RPT. The primary outcome was the number of relapses.
  
  
  
  In the base-case scenario, standard therapy resulted in fewer relapses; improvement in 2-month culture conversion rates in the RPT arm did not change this result. However, while RPT has better sterilizing ability during months 3 and 4 (as observed in the mouse model), the 4-month regimen results in fewer relapses.
  
  
  
  Higher 2-month culture conversion rates are neither sufficient nor necessary for making a theoretical 4-month anti-tuberculosis treatment regimen advantageous.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, Georgia, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Holland
authors.affiliation: Global Health, Population, and Nutrition, FHI306, North Carolina, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Hamilton
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Stout
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D003661:Decision Support Techniques; D004977:Ethambutol / Q000627:therapeutic use; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008390:Markov Chains; D011718:Pyrazinamide / Q000627:therapeutic use; D012008:Recurrence; D012293:Rifampin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine