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TUBERCULOSIS TREATMENT INTERMITTENCY IN THE CONTINUATION PHASE AND MORTALITY IN HIV-POSITIVE PERSONS RECEIVING ANTIRETROVIRAL THERAPY
HIV
Intermittent treatment
TB maintenance treatment
Tuberculosis
Tuberculosis treatment
Author
Affilliation
Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán. Departamento de Infectología. Mexico City, Mexico.
Vanderbilt University Medical Center. Nashville, TN, USA.
Vanderbilt University Medical Center. Nashville, TN, USA.
Vanderbilt University Medical Center. Nashville, TN, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.
Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander Von Humboldt. Lima, Peru.
Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander Von Humboldt. Lima, Peru.
University of Chile. Fundación Arriarán. Santiago, Chile.
Hospital Escuela and Instituto Hondureño de Seguridad Social. Tegucigalpa, Honduras.
Vanderbilt University Medical Center. Nashville, TN, USA.
Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán. Departamento de Infectología. Mexico City, Mexico.
Brigham and Women's Hospital. Division of Global Health Equity. Boston, MA, USA / Le Groupe Haïtien d'Etude du Sarcome de Kaposi Et Des Infections Opportunistes (GHESKIO). Port-au-Prince, Haiti.
Le Groupe Haïtien d'Etude du Sarcome de Kaposi Et Des Infections Opportunistes (GHESKIO). Port-au-Prince, Haiti.
Vanderbilt University Medical Center. Nashville, TN, USA.
Vanderbilt University Medical Center. Nashville, TN, USA.
Vanderbilt University Medical Center. Nashville, TN, USA.
Vanderbilt University Medical Center. Nashville, TN, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.
Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander Von Humboldt. Lima, Peru.
Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander Von Humboldt. Lima, Peru.
University of Chile. Fundación Arriarán. Santiago, Chile.
Hospital Escuela and Instituto Hondureño de Seguridad Social. Tegucigalpa, Honduras.
Vanderbilt University Medical Center. Nashville, TN, USA.
Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán. Departamento de Infectología. Mexico City, Mexico.
Brigham and Women's Hospital. Division of Global Health Equity. Boston, MA, USA / Le Groupe Haïtien d'Etude du Sarcome de Kaposi Et Des Infections Opportunistes (GHESKIO). Port-au-Prince, Haiti.
Le Groupe Haïtien d'Etude du Sarcome de Kaposi Et Des Infections Opportunistes (GHESKIO). Port-au-Prince, Haiti.
Vanderbilt University Medical Center. Nashville, TN, USA.
Abstract
Background: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described.
Methods: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation.
Results: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20).
Conclusions: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.
Keywords
ARTHIV
Intermittent treatment
TB maintenance treatment
Tuberculosis
Tuberculosis treatment
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