title: Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons.
abstract: Compare the effectiveness, tolerability, and safety of 3 months of weekly rifapentine and isoniazid under direct observation (3HP) versus 9 months of daily isoniazid (9H) in HIV-infected persons.
  
  
  
  Prospective, randomized, and open-label noninferiority trial.
  
  
  
  The United States , Brazil, Spain, Peru, Canada, and Hong Kong.
  
  
  
  HIV-infected persons who were tuberculin skin test positive or close contacts of tuberculosis cases.
  
  
  
  3HP versus 9H.
  
  
  
  The effectiveness endpoint was tuberculosis; the noninferiority margin was 0.75%. The tolerability endpoint was treatment completion; the safety endpoint was drug discontinuation because of adverse drug reaction.
  
  
  
  Median baseline CD4 cell counts were 495 (IQR 389-675) and 538 (IQR 418-729) cells/μl in the 3HP and 9H arms, respectively (P = 0.09). In the modified intention-to-treat analysis, there were two tuberculosis cases among 206 persons [517 person-years (p-y) of follow-up] in the 3HP arm (0.39 per 100 p-y) and six tuberculosis cases among 193 persons (481 p-y of follow-up) in the 9H arm (1.25 per 100 p-y). Cumulative tuberculosis rates were 1.01 versus 3.50% in the 3HP and 9H arms, respectively (rate difference: -2.49%; upper bound of the 95% confidence interval of the difference: 0.60%). Treatment completion was higher with 3HP (89%) than 9H (64%) (P < 0.001), and drug discontinuation because of an adverse drug reaction was similar (3 vs. 4%; P = 0.79) in 3HP and 9H, respectively.
  
  
  
  Among HIV-infected persons with median CD4 cell count of approximately 500 cells/μl, 3HP was as effective and safe for treatment of latent Mycobacterium tuberculosis infection as 9H, and better tolerated.
authors.affiliation: aVanderbilt University School of Medicine, Nashville, Tennessee bCenters for Disease Control and Prevention, Atlanta, Georgia, USA cHospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain dInstituto Nacional de Infectologia, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil eAsociacion Civil Impacta Salud y Educacion, Lima, Peru fVeterans Affairs Medical Center gGeorge Washington University, Washington, District of Columbia hUniversity of California at San Diego, California iJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sterling
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Scott
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miro
authors.forename: Guilherme
authors.initials: G
authors.lastname: Calvet
authors.forename: Alberto
authors.initials: A
authors.lastname: La Rosa
authors.forename: Rosa
authors.initials: R
authors.lastname: Infante
authors.forename: Michael P
authors.initials: MP
authors.lastname: Chen
authors.forename: Debra A
authors.initials: DA
authors.lastname: Benator
authors.forename: Fred
authors.initials: F
authors.lastname: Gordin
authors.forename: Constance A
authors.initials: CA
authors.lastname: Benson
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.forename: M Elsa
authors.initials: ME
authors.lastname: Villarino
mesh_terms: D000293:Adolescent; D000328:Adult; D000569:Americas; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001208:Asia; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011446:Prospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine