ArticlesEffect 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
Introduction
Isoniazid preventive therapy has long been recognised as an effective intervention for reducing the risk of tuberculosis at the individual and population level.1 Studies in people with HIV infection show that preventive therapy reduces tuberculosis rates, particularly in those with positive tuberculin skin tests.2 Evidence from observational studies in Brazil and South Africa have shown substantial reductions in tuberculosis risk in patients with HIV who received both isoniazid and antiretroviral therapy.3, 4 Although use of isoniazid preventive therapy has been recommended by WHO since 1998,5 uptake of this intervention in countries with high burdens of HIV and tuberculosis has been extremely poor.6 Brazil has a moderate tuberculosis rate (38 per 100 000 in 2011),6 and in Rio de Janeiro, a city where 10% of cases are co-infected with HIV, the prevalence was 95·3 per 100 000 in 2009. Tuberculosis continues to be a leading cause of illness and death in people with HIV infection.7 We sought to determine the effect of an intervention to increase use of isoniazid preventive therapy, and to assess the subsequent effect on rates of tuberculosis and death in HIV-infected individuals in Brazil, where antiretroviral therapy has been freely available through the public sector since 1996.
Section snippets
Study design and participants
The design of the Tuberculosis/HIV in Rio de Janeiro (THRio) study has been previously described.8 It was a stepped-wedge, cluster randomised trial in which 29 of the 51 clinics providing antiretroviral therapy in Rio de Janeiro (representing 57% of all HIV-infected patients in the region) were randomly assigned to the date when a training intervention would be introduced. Clinics ranged in size from 121 to 1749 patients, and were chosen because they were under the administrative control of the
Results
The initial THRio cohort consisted of 17 413 patients with HIV, 11 629 who had visited study clinics before the trial started and 5784 who entered clinical care between Sept 1, 2005, and Aug 31, 2009 (figure). 4597 (26%) patients were excluded from the analysis for the following reasons: diagnosis of tuberculosis before the study start date plus 60 days (n=3566), had isoniazid preventive therapy before the study plus 60 days (n=920), or died within 60 days of study start (n=111). After these
Discussion
The THRio intervention of training clinicians to screen for tuberculosis, to do tuberculin skin testing, and to offer isoniazid preventive therapy had a modest effect on tuberculosis incidence (13% reduction) and a larger and statistically significant effect on tuberculosis or death (24% reduction). After adjustment for important covariates such as age, sex, CD4 count, and receipt of antiretroviral therapy, during the intervention there was a 27% reduction in tuberculosis and a 31% reduction in
References (29)
- et al.
6-month versus 36-month isoniazid preventive therapy for tuberculosis in adults with HIV infection in Botswana: a randomized, double-blind, placebo-controlled trial
Lancet
(2011) - et al.
Isoniazid prophylaxis among Alaskan Eskimos: a final report of the bethel isoniazid studies
Am Rev Respir Dis
(1979) - et al.
Treatment of latent tuberculosis infection in HIV infected persons
Cochrane Database Syst Rev
(2010) - et al.
The impact of antiretroviral therapy and isoniazid preventive therapy on tuberculosis incidence in HIV-infected patients in Rio de Janeiro, Brazil
AIDS
(2007) - et al.
Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort
AIDS
(2009) Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. WHO guidelines 2011. Department of HIV/AIDS. Stop TB Department
(2011)Global tuberculosis report 2012
(2012)Secretaria de Vigilância em Saúde
- et al.
Statistical design of THRio: a phased implementation clinic-randomized study of a tuberculosis preventive therapy intervention
Clin Trials
(2007) - et al.
III Brazilian Thoracic Association Guidelines on tuberculosis
J Bras Pneumol
(2009)