title: Long-term protection from isoniazid preventive therapy for tuberculosis in HIV-infected patients in a medium-burden tuberculosis setting: the TB/HIV in Rio (THRio) study.
abstract: BACKGROUND
  The duration of protection against tuberculosis provided by isoniazid preventive therapy is not known for human immunodeficiency virus (HIV)-infected individuals living in settings of medium tuberculosis incidence.
  
  
  METHODS
  We conducted an individual-level analysis of participants in a cluster-randomized, phased-implementation trial of isoniazid preventive therapy. HIV-infected patients who had positive tuberculin skin tests (TSTs) were followed until tuberculosis diagnosis, death, or administrative censoring. Nelson-Aalen cumulative hazard plots were generated and hazards were compared using the log-rank test. Cox proportional hazards models were fitted to investigate factors associated with tuberculosis diagnosis.
  
  
  RESULTS
  Between 2003 and 2009, 1954 patients with a positive TST were studied. Among these, 1601 (82%) initiated isoniazid. Overall tuberculosis incidence was 1.39 per 100 person-years (PY); 0.53 per 100 PY in those who initiated isoniazid and 6.52 per 100 PY for those who did not (adjusted hazard ratio [aHR], 0.17; 95% confidence interval [CI], .11-.25). Receiving antiretroviral therapy at time of a positive TST was associated with a reduced risk of tuberculosis (aHR, 0.69; 95% CI, .48-1.00). Nelson-Aalen plots of tuberculosis incidence showed a constant risk, with no acceleration in 7 years of follow-up for those initiating isoniazid preventive therapy.
  
  
  CONCLUSIONS
  Isoniazid preventive therapy significantly reduced tuberculosis risk among HIV-infected patients with a positive TST. In a medium-prevalence setting, 6 months of isoniazid in HIV-infected patients with positive TST reduces tuberculosis risk over 7 years of follow-up, in contrast to results of studies in higher-burden settings in Africa.
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Golub
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cohn
authors.affiliation: Municipal Health Secretariat.
authors.forename: Valeria
authors.initials: V
authors.lastname: Saraceni
authors.affiliation: Municipal Health Secretariat Instituto de Pesquisa Clinica Evandro Chagas-FIOCRUZ.
authors.forename: Solange C
authors.initials: SC
authors.lastname: Cavalcante
authors.affiliation: Programa de Computação Científica-FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Pacheco
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Moulton
authors.affiliation: Municipal Health Secretariat Federal University of Rio de Janeiro, Brazil.
authors.forename: Betina
authors.initials: B
authors.lastname: Durovni
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001938:Brazil / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016016:Proportional Hazards Models; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid
keywords: HIV; durability; isoniazid; preventive therapy; tuberculosis