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

Summary Background Preventive therapy for tuberculosis among HIV-infected patients is effective but has not been widely implemented in moderate/high-burden settings. Objectives To determine the impact of widespread use of isoniazid preventive therapy on rates of tuberculosis and death in HIV-infected individuals in Brazil. Design Stepped wedge, cluster randomized trial Participants Patients actively enrolled in 29 HIV clinics in Rio de Janeiro, Brazil Control period Standard of care Intervention period Staff training in tuberculosis screening, performance of tuberculin skin tests and use of isoniazid preventive therapy. Randomization 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. Results 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, 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 moderate tuberculosis incident settings is achievable and should be strongly considered in Brazil and elsewhere. Trial registration This trial is registered at clinicaltrials.gov (NCT00107887) Funding Bill & Melinda Gates Foundation; National Institutes of Health

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

“…22,[28][29][30][31] Evidence for the added value of IPT in patients receiving ART was mostly from patients with CD4+ counts of less than 500 cells per cubic millimeter. [32][33][34][35][36][37][38] Our data are consistent with these previous studies that showed that IPT and ART have additive efficacy with respect to the prevention of tuberculosis and that suggested that the two therapies should be given concomitantly. They also highlight for countries that are reluctant to recommend IPT that isoniazid can be prescribed safely when given early in the course of HIV disease.…”

6-year follow-up of 522 HIV-positive individuals screened forMycobacterium tuberculosisinfection in Denmark

“…We can conclude that the QFT-IT test with a NPV of a 100% can be considered a safe test for ruling out risk of TB among immunocompetent HIV-positive individuals in a low endemic country like Denmark. Based on our study and others, there is an increased risk of progressing to TB in QFT-IT-positive HIV-positive individuals that should not be ignored [9].…”

“…Isoniazid preventive treatment (IPT) has shown to be effective in preventing reactivation of TB in HIV positive individuals [7][8][9], and the treatment has been recommended by the World Health Organization and the US Centers for Disease Control and Prevention [10].…”

“…The evidence to recommend IPT to HIV-positive patients is overwhelming even in the presence of effective antiretroviral treatment [8][9][10]. This combined effect is shown in high-burden countries, whereas data from low-endemic regions are limited.…”

“…To reach elimination (defined as fewer than one sputum smear-positive case per million inhabitants), countries should ensure that diagnosis and treatment of latent TB infection (LTBI) supplements detection and treatment of active TB disease [7][8][9][10]. …”