Preventive therapy for tuberculosis among HIV-infected patients is effective but has not been widely implemented in moderate/high-burden settings.
To determine the impact of widespread use of isoniazid preventive therapy on rates of tuberculosis and death in HIV-infected individuals in Brazil.
Stepped wedge, cluster randomized trial
Patients actively enrolled in 29 HIV clinics in Rio de Janeiro, Brazil
Standard of care
Staff training in tuberculosis screening, performance 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 September 1 2005.
Main outcome measures
Tuberculosis incidence alone or combined with death in the control versus intervention periods through August 31 2009.
Among 17,413 patients in the THRio 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 19/100 person-years to 59/100 person-years, and from 36/100 person-years to 144/100 person-years for those eligible for isoniazid preventive therapy. In the control period, 221 tuberculosis cases were diagnosed (1·31/100 person-years) compared to 254 (1·10/100 person-years) in the intervention (unadjusted hazard ratio (HR)=0·87;95%CI:0·69–1·10). Rates of tuberculosis incidence or death were 3·64 and 3·04/100 person-years, respectively (HR=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 (95%CI:0·57–0·83). Among 12,196 patients remaining in care (secondary analyses, 399 tuberculosis cases and 656 deaths), the adjusted HR of tuberculosis alone and combined with death were 0·42 (95%CI:0·29–0·60) and 0·45 (95%CI:0·35–0·56), respectively,
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 moderate tuberculosis incident settings is achievable and should be strongly considered in Brazil and elsewhere.
This trial is registered at clinicaltrials.gov (NCT00107887)
Bill & Melinda Gates Foundation; National Institutes of Health