title: Effect of improved tuberculosis screening and isoniazid preventive therapy on incidence of tuberculosis and death in patients with HIV in clinics in Rio de Janeiro, Brazil: a stepped wedge, cluster-randomised trial.
abstract: BACKGROUND
  Preventive therapy for tuberculosis in patients with HIV is effective, but it has not been widely implemented in moderate or high-burden settings. We assessed the effect of widespread use of isoniazid preventive therapy on rates of tuberculosis and death in people with HIV in Brazil.
  
  
  METHODS
  We did a stepped wedge, cluster-randomised trial with patients actively enrolled in 29 HIV clinics in Rio de Janeiro. Clinic staff were trained in tuberculosis screening, use of tuberculin skin tests, and use of isoniazid preventive therapy. Clinics were randomly allocated a date to begin the intervention period, with two clinics beginning the intervention every 2 months starting from Sept 1, 2005. The primary outcome was tuberculosis incidence alone or combined with death in the control versus intervention periods until Aug 31, 2009. This trial is registered at ClinicalTrials.gov, number NCT00107887.
  
  
  RESULTS
  Of 17,413 patients in the cohort, 12,816 were eligible for the intervention. Overall, there were 475 tuberculosis cases and 838 deaths. The intervention increased the rate of patients receiving skin tests from 19 per 100 person-years to 59 per 100 person-years, and from 36 per 100 person-years to 144 per 100 person-years for those eligible for isoniazid preventive therapy. In the control period, 221 cases of tuberculosis were diagnosed (1.31 per 100 person-years) compared with 254 (1.10 per 100 person-years) in the intervention period (unadjusted hazard ratio [HR] 0.87; 95% CI 0.69-1.10). Rates of tuberculosis incidence or death were 3.64 and 3.04 per 100 person-years, respectively (0.76; 95% CI 0.66-0.87). When adjusted for age, sex, entry CD4 count, and use of antiretroviral therapy, the HR for tuberculosis was 0.73 (95% CI 0.54-0.99) and for tuberculosis or death was 0.69 (0.57-0.83).
  
  
  CONCLUSIONS
  Operational training aimed at increasing tuberculosis screening, provision of tuberculin skin tests, and use of isoniazid preventive therapy in Brazilian HIV clinics significantly reduced incident tuberculosis and death. Thus, scale-up of preventive therapy for HIV-infected patients in settings of moderate tuberculosis incidence is achievable and should be widely implemented in Brazil and elsewhere.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation and the National Institutes of Health.
authors: Municipal Health Secretariat, Rio de Janeiro, Brazil; Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Betina
authors: B
authors: Durovni
authors: Valeria
authors: V
authors: Saraceni
authors: Lawrence H
authors: LH
authors: Moulton
authors: Antonio G
authors: AG
authors: Pacheco
authors: Solange C
authors: SC
authors: Cavalcante
authors: Bonnie S
authors: BS
authors: King
authors: Silvia
authors: S
authors: Cohn
authors: Anne
authors: A
authors: Efron
authors: Richard E
authors: RE
authors: Chaisson
authors: Jonathan E
authors: JE
authors: Golub
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001938:Brazil / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents; D007538:Isoniazid
references: J Bras Pneumol. 2009 Oct;35(10):1018-48
references: 19918635
references: PLoS One. 2012;7(3):e34156
references: 22479548
references: Cochrane Database Syst Rev. 2010 Jan 20;(1):CD000171
references: 20091503
references: N Engl J Med. 2011 Oct 20;365(16):1482-91
references: 22010914
references: Am Rev Respir Dis. 1979 May;119(5):827-30
references: 453704
references: Int J Tuberc Lung Dis. 2009 Aug;13(8):982-8
references: 19723378
references: Lancet. 2011 May 7;377(9777):1588-98
references: 21492926
references: PLoS Med. 2012;9(7):e1001270
references: 22911011
references: N Engl J Med. 2011 Jul 7;365(1):11-20
references: 21732833
references: N Engl J Med. 2011 Oct 20;365(16):1471-81
references: 22010913
references: Clin Trials. 2004;1(3):297-305
references: 16279255
references: AIDS. 2007 Jul 11;21(11):1441-8
references: 17589190
references: Clin Trials. 2007;4(2):190-9
references: 17456522
references: AIDS. 2010 Nov;24 Suppl 5:S49-56
references: 21079428
references: AIDS. 2010 Nov;24 Suppl 5:S5-13
references: 21079429
references: AIDS. 2009 Mar 13;23(5):631-6
references: 19525621
references: N Engl J Med. 2011 Oct 20;365(16):1492-501
references: 22010915
references: Stat Med. 2001 Feb 15;20(3):351-65
references: 11180306