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PREDICTORS OF EARLY MORTALITY AND EFFECTIVENESS OF ANTIRETROVIRAL THERAPY IN TB-HIV PATIENTS FROM BRAZIL
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Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Programa de Pós-Graduação em Pesquisa Clínica em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Laureate Universities. Universidade Salvador. Salvador, BA, Brasil / University of Cape Town. Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. Cape Town, South Africa / Vanderbilt University. School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Programa de Pós-Graduação em Pesquisa Clínica em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Laureate Universities. Universidade Salvador. Salvador, BA, Brasil / University of Cape Town. Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. Cape Town, South Africa / Vanderbilt University. School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Programa de Pós-Graduação em Pesquisa Clínica em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil.
Abstract
Background: The implementation of antiretroviral (ARV) therapy caused a significant decrease in HIV associated mortality worldwide. Nevertheless, mortality is still high among people living with HIV/AIDS and tuberculosis (TB). ARV-naïve HIV patients coinfected with tuberculosis (TB) have more options to treat both diseases concomitantly. Nevertheless, some TB-HIV patients undertaking ARVs (ARV-experienced) are already failing the first line efavirenzbased regimen and seem to display different response to second line ARV therapy and exhibit other predictors of mortality. Methods: We performed a retrospective cohort study including 273 patients diagnosed with TB-HIV and treated at a referral center in Rio de Janeiro, Brazil, between 2008 and 2016. Multivariate analysis and Cox regression models were used to evaluate the effectiveness of ARV
therapy regimens (viral load [VL] <80 copies from the 4th to 10th months after TB therapy introduction) and to identify predictors of early mortality (100 days after TB therapy initiation) considering ARV-naïve and ARV-experienced patients adjusting for sociodemographic, clinical and therapeutic covariates. Findings: Survival analysis included 273 patients, out of whom 154 (56.4%) were ARV-naïve and 119 (43.6%) were ARV-experienced. Seven deaths occurred within 6 months of anti-TB treatment, 4 in ARV-naïve and 3 in ARV-experienced patients. Multivariate analysis revealed that in ARV-naïve patients, the chance of death was substantially higher in patients who developed immune reconstitution inflammatory syndrome during the study follow up (HR = 40.6, p<0.01). For ARV-experienced patients, similar analyses failed to identify factors significantly associated with mortality. Variables independently associated with treatment failure for the ARV-naïve group were previous TB (adjusted OR [aOR] = 6.1 p = 0.03) and alcohol abuse (aOR = 3.7 p = 0.01). For ARV-experienced patients, a ritonavir boosted. Protease Inhibitor-based regimen resulted in a 2.6 times higher risk of treatment failure compared to the use of efavirenz based ARV regimens (p = 0.03) and High baseline HIV VL (p =0.03) were predictors of treatment failure. Conclusions: Risk factors for mortality and ARV failure were different for ARV-naïve and ARV-experienced patients. The latter patient group should be targeted for trials with less toxic and rifampicin-compatible drugs to improve TB-HIV treatment outcomes and prevent death.
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