Adherence to tuberculosis preventive therapy measured by urine metabolite testing among people with HIV.

OBJECTIVES: Tuberculosis preventive therapy for people living with HIV is effective, widely recommended, and increasingly prescribed, but completion rates are less than ideal, and adherence is not typically monitored. We sought to quantify adherence to isoniazid preventive therapy using a urine metabolite assay. DESIGN: Two cross-sectional surveys. SETTING: Rio de Janeiro, Brazil, 2008-2009; and Northwest Province, South Africa, 2018-2019. PARTICIPANTS: Two hundred and three Brazilian and 93 South African patients attending HIV clinics with active prescriptions for isoniazid preventive therapy MAIN OUTCOME MEASURES:: Self-reported isoniazid adherence, paired with semiquantitative measurement of urine isoniazid metabolites. RESULTS: By self-report, 90% of patients [95% confidence interval (CI) 86-93%] reported having taken a dose of isoniazid on the day of enrollment or the preceding day, and 91% (95% CI 87-94%) reported missing an average of one dose or fewer per week. By urine testing, only 65% (95% CI 59-70%) of all patients, and 69% (95% CI 63-74%) of those who reported having taken isoniazid on the current or preceding day, had detectable urine metabolites (expected in 95% of patients at 24 h). Longer time since starting preventive therapy was independently associated with a negative urine test for isoniazid metabolites (adjusted prevalence ratio 1.11 per month of isoniazid, 95% CI 1.05-1.18). CONCLUSION: Adherence to isoniazid preventive therapy among patients with HIV in Brazil and South Africa is inadequate, is overestimated by self-report, and declines with time on treatment. Shorter regimens for TB preventive therapy may improve adherence and completion, but adherence support for all patients may be necessary.

Recurrent tuberculosis in HIV-infected patients in Rio de Janeiro, Brazil.

BACKGROUND/OBJECTIVE: The risk of recurrent tuberculosis may increase in HIV-infected patients due to exogenous reinfection. We measured the frequency of and determined risk factors for recurrent tuberculosis in a cohort of HIV-infected patients in Rio de Janeiro, Brazil. METHODS: Data were abstracted from medical records of HIV-infected patients attending 29 HIV clinics between 1998 and 2007. Patients analyzed were those who had no tuberculosis history prior to their first HIV clinic visit and who had at least one episode of tuberculosis after entry. Incidence rate ratios compared incidence rates between risk groups and Cox proportional hazards regression models evaluated unadjusted and adjusted associations. RESULTS: Among 1080 HIV-infected patients with tuberculosis, 96 (8.9%) developed a recurrent diagnosis. The median time between diagnoses was 2.4 years. Fewer patients with recurrent tuberculosis had completed their initial 6-month course of tuberculosis treatment compared with patients without recurrence (78 versus 86%; P = 0.02). For patients who completed therapy, the incidence rate of recurrence was 2.5/100 versus 9.0/100 person-years for noncompleters (incidence rate ratio, 3.60; 95% confidence interval, 1.92-6.32). In multivariate modeling, initial tuberculosis treatment completion, receipt of antiretroviral therapy, and CD4 cell count more than 200 mm any time after the initial diagnosis were associated with a significantly decreased hazard of recurrence. CONCLUSION: Tuberculosis recurrence rates were high in this HIV-infected population. Completion of initial tuberculosis therapy, use of antiretroviral therapy, and increases in CD4 cell counts were associated with lower recurrence rates. Use of secondary preventive therapy might be warranted to reduce the burden of tuberculosis in patients with HIV infection.