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

Betina Durovni, Valeria Saraceni, Lawrence Hale Moulton, Antonio G. Pacheco, Solange C. Cavalcante, Bonnie S. King, Silvia Cohn, Anne Efron, Richard E Chaisson, Jonathan E Golub

Research output: Contribution to journalArticle

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 17413 patients in the cohort, 12816 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). Interpretation: 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. Funding: Bill & Melinda Gates Foundation and the National Institutes of Health.

Original languageEnglish (US)
Pages (from-to)852-858
Number of pages7
JournalLancet Infectious Diseases
Volume13
Issue number10
DOIs
StatePublished - Oct 2013

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Isoniazid
Brazil
Tuberculosis
HIV
Incidence
Therapeutics
Skin Tests
Tuberculin Test
National Institutes of Health (U.S.)
CD4 Lymphocyte Count

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

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. / Durovni, Betina; Saraceni, Valeria; Moulton, Lawrence Hale; Pacheco, Antonio G.; Cavalcante, Solange C.; King, Bonnie S.; Cohn, Silvia; Efron, Anne; Chaisson, Richard E; Golub, Jonathan E.

In: Lancet Infectious Diseases, Vol. 13, No. 10, 10.2013, p. 852-858.

Research output: Contribution to journalArticle

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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 17413 patients in the cohort, 12816 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). Interpretation: 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. Funding: Bill & Melinda Gates Foundation and the National Institutes of Health.",
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AU - Saraceni, Valeria

AU - Moulton, Lawrence Hale

AU - Pacheco, Antonio G.

AU - Cavalcante, Solange C.

AU - King, Bonnie S.

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AU - Chaisson, Richard E

AU - Golub, Jonathan E

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