Contextualizing and optimizing novel strategies to improve the latent TB continuum of care: Insights from people living with HIV and health care providers in Brazil.

Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP's perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality.

Brief Report: Yield of Repeat Tuberculin Skin Testing for People Living With HIV in Brazil.

OBJECTIVES: In Brazil, annual tuberculin skin tests (TSTs) are recommended for people living with HIV (PLWH) with CD4 >350, with tuberculosis preventive therapy provided on test conversion. We aimed to determine the yield of repeat TSTs for PLWH. DESIGN: Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT) to prevent tuberculosis (TB). METHODS: We analyzed data from newly registered PLWH with negative baseline TST results. We calculated the number of TST conversions after 1 and/or 2 years among patients eligible for follow-up TSTs, the proportion of converters initiating IPT, and incidence of TB/death. RESULTS: Among 1770 PLWH with a negative baseline TST, 679 (38%) were female and median age was 36 years (IQR 29-43). Eighty-six (5%) developed TB or died within 1 year. Among 1684 eligible for a follow-up 1-year TST, 582 (35%) were tested and 53 (9%) were positive. Forty-nine converters (92%) started IPT. Of 529 patients with a negative 1-year TST, 7 (1%) developed TB or died over the following year. Of 522 patients eligible for a 2-year TST, 158 (30%) were tested and 13 (8%) were positive. Ten converters (77%) started IPT. Of 1102 patients who did not receive a 1-year TST, 33 (3%) developed TB or died. Of the 1069 patients eligible for a 2-year TST, 259 (24%) were tested and 34 (13%) were positive. Thirty converters (88%) started IPT. CONCLUSIONS: In this cohort of PLWH in Brazil, TST conversion was high among those retested, but only 48% received a follow-up TST within 2 years.

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.

CD4+ cell count stratification to guide tuberculosis preventive therapy for people living with HIV.

OBJECTIVES: In 2018, Brazilian guidelines changed to recommend tuberculosis (TB) preventive therapy for all people with HIV and a CD4 cell count 350 cells/µl or less, but only for those with a positive tuberculin skin test (TST) if CD4 cell count is than 350 cells/µl. We determined the potential effectiveness of CD4-based guidelines for TB testing and preventive therapy. DESIGN: Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT). METHODS: We analyzed data from 4114 newly registered patients with HIV in 29 clinics followed until TB diagnosis, death, or administrative censoring. We compared incidence rates of TB and TB/death between CD4, TST, IPT, and antiretroviral therapy categories. RESULTS: Initial CD4 cell count was 350 cells/µl or less in 2138 (52%) and more than 350 cells/µl in 1976 (48%) patients. TST was performed for 2922 (71%), of whom 657 (16%) were TST-positive [278 (13%) CD4 ≤ 350 vs. 379 (19%) CD4 > 350]. A total of 619 (15%) received IPT and 2806 (68%) received antiretroviral therapy. For patients with CD4 cell count 350 cells/µl or less who did not receive IPT, the incidence rate of TB was 1.79/100 person-years (pys) and TB/death was 3.89/100 pys. For patients with CD4 cell count more than 350 who did not receive IPT, the incidence rates of TB and TB/death were 0.57/100 and 1.49/100 pys for TST-negatives, and 1.05/100 and 1.64/100 pys for TST-unknowns. CONCLUSION: TB incidence was high among all patients who did not receive IPT, including those with CD4 cell count more than 350 cells/µl and negative or unknown TST results. TB preventive therapy should be provided to all people living with HIV in medium burden settings, regardless of CD4 cell count and TST status.

Cost-effectiveness of QuantiFERON-TB Gold In-Tube versus tuberculin skin test for diagnosis and treatment of Latent Tuberculosis Infection in primary health care workers in Brazil.

OBJECTIVES: The goal of this study was to perform a cost-effectiveness analysis from the public health system perspective, comparing five strategies for Latent Tuberculosis Infection (LTBI) diagnosis in primary health care workers in Brazil. DESIGN: Analytical model for decision making, characterized by cost-effectiveness analysis. SETTING: Primary Care Level, considering primary health care workers in Brazil. PARTICIPANTS: An analytical model for decision making, characterized by a tree of probabilities of events, was developed considering a hypothetical cohort of 10,000 primary health care workers, using the software TreeAge Pro™ 2013 to simulate the clinical and economic impacts of new diagnostic technology (QuantiFERON®-TB Gold in-Tube) versus the traditional tuberculin skin test. METHODS: This model simulated five diagnostic strategies for LTBI in primary health care workers (HCW) in Brazil: tuberculin skin testing using ≥5 mm cut-off, tuberculin skin testing ≥10 mm cut-off, QuantiFERON®-TB Gold in-Tube, tuberculin skin testing using ≥5 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive, tuberculin skin testing using ≥10 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measures are the number of individuals correctly classified by the test and the number of Tuberculosis cases avoided. RESULTS: The most cost-effective strategy was the tuberculin skin test considering ≥10mm cut-off. The isolated use of the QuantiFERON®-TB Gold In-Tube revealed the strategy of lower efficiency with incremental cost-effectiveness ratio (ICER) of US$ 146.05 for each HCW correctly classified by the test. CONCLUSIONS: The tuberculin skin test using ≥10 mm cut-off was the most cost-effective strategy in the diagnosis of Latent Tuberculosis Infection in primary health care works in Brazil.

Tuberculosis fatality rates in the city of Campinas - São Paulo, Brazil, from 2001 to 2009.

INTRODUCTION: The mortality rate among tuberculosis patients (TB fatality) has been attributed to irregular chemotherapy, delay in diagnosis, multidrug resistance, and HIV coinfection. OBJECTIVE: To analyze TB fatality rates by sex, clinical presentation and HIV coinfection in Campinas, São Paulo, Brazil. METHODS: Cohorts of residents in the city of Campinas who either died during treatment for tuberculosis or had the disease confirmed after death were divided into three intervals: 2001-2003, 2004-2006, and 2007-2009. Data were obtained from the database of the Tuberculosis Surveillance System of the University of Campinas, and notifications were gathered through TB-WEB Health São Paulo Secretary. Statistical significance was determined using a chi-square test, considering p < 0.05. RESULTS: Between 2001 and 2009, 3,416 TB patients were diagnosed: 2,827 (82.8%) were new TB cases and 589 (17.2%) were retreatments. Between the first and second triennium, the number of new patients decreased by 18%, and 23% among retreatments. Between the second and third intervals, the reduction was 5% and 21%, respectively. General case fatality rate declined from 11.4% to 9.9% across intervals, and was most significant among patients that had previously abandoned treatment (17.3% to 5.1%). Fatality rates among patients coinfected with TB-AIDS were 2-3 times that of patients not infected with TB-AIDS throughout the intervals. Fatality between the first and third triennium among TB-AIDS co-infected patients declined (24.8% to 19.5%), while increasing slightly among non-AIDS TB patients (7.3% to 8%) during this period. CONCLUSION: Though mortality among TB-AIDS patients declined from 2001-2009, rates among non-AIDS TB remained stagnant. Improved TB diagnosis and treatment is needed to further decrease TB mortality in Campinas.

Tuberculosis fatality rates in the city of Campinas - São Paulo, Brazil, from 2001 to 2009 / Taxas de letalidade por tuberculose na cidade de Campinas, São Paulo, Brasil, de 2001 a 2009

ABSTRACT: Introduction: The mortality rate among tuberculosis patients (TB fatality) has been attributed to irregular chemotherapy, delay in diagnosis, multidrug resistance, and HIV coinfection. Objective: To analyze TB fatality rates by sex, clinical presentation and HIV coinfection in Campinas, São Paulo, Brazil. Methods: Cohorts of residents in the city of Campinas who either died during treatment for tuberculosis or had the disease confirmed after death were divided into three intervals: 2001-2003, 2004-2006, and 2007-2009. Data were obtained from the database of the Tuberculosis Surveillance System of the University of Campinas, and notifications were gathered through TB-WEB Health São Paulo Secretary. Statistical significance was determined using a chi-square test, considering p < 0.05. Results: Between 2001 and 2009, 3,416 TB patients were diagnosed: 2,827 (82.8%) were new TB cases and 589 (17.2%) were retreatments. Between the first and second triennium, the number of new patients decreased by 18%, and 23% among retreatments. Between the second and third intervals, the reduction was 5% and 21%, respectively. General case fatality rate declined from 11.4% to 9.9% across intervals, and was most significant among patients that had previously abandoned treatment (17.3% to 5.1%). Fatality rates among patients coinfected with TB-AIDS were 2-3 times that of patients not infected with TB-AIDS throughout the intervals. Fatality between the first and third triennium among TB-AIDS co-infected patients declined (24.8% to 19.5%), while increasing slightly among non-AIDS TB patients (7.3% to 8%) during this period. Conclusion: Though mortality among TB-AIDS patients declined from 2001-2009, rates among non-AIDS TB remained stagnant. Improved TB diagnosis and treatment is needed to further decrease TB mortality in Campinas.

RESUMO: Introdução: A letalidade por tuberculose tem sido atribuída à quimioterapia irregular, à demora no diagnóstico, à multidrogarresistência, à coinfecção com o vírus da imunodeficiência humana (HIV). Objetivo: Analisar letalidade por tuberculose segundo sexo, apresentação clínica, presença da coinfecção pelo HIV, em Campinas, São Paulo, Brasil. Metodologia: Foram verificadas coortes de residentes em Campinas que morreram durante tratamento para tuberculose e aqueles notificados após óbito, agrupados em três intervalos: 2001-2003, 2004-2006 e 2007-2009. As informações foram obtidas no Banco de Dados para Vigilância da Tuberculose da Universidade Estadual de Campinas (UNICAMP), com captação das notificações no Sistema de Notificação e Acompanhamento de Casos de Tuberculose da Secretaria Estadual de Saúde de São Paulo. A significância estatística foi verificada pelo teste χ2 considerando p < 0,05. Resultados: Entre 2001 e 2009, foram diagnosticados 3.416 pacientes com tuberculose: 2.827 (82,8%) sem tratamento anterior e 589 (17,2%) com retratamentos. Entre o primeiro e o segundo triênio, o número de pacientes novos diminuiu 18% sem tratamento anterior e 23% entre retratamentos. Entre o segundo e o terceiro intervalo, a redução foi de 5 e 21%, respectivamente. A letalidade geral declinou de 11,4 para 9,9%, diferença mais significante entre os que haviam abandonado tratamento anteriormente (17,3 para 5,1%). A letalidade entre pacientes com coinfecção tuberculose-síndrome da imunodeficiência adquirida (Aids) foi 2-3 vezes maior que entre tuberculose sem aids durante todo o período estudado. A letalidade entre o primeiro e o terceiro triênio declinou no grupo com tuberculose-aids (24,8 para 19,5%), enquanto teve ligeiro aumento entre tuberculose sem aids (7,3 para 8%). Conclusão: Embora a mortalidade entre pacientes com tuberculose-aids tenha diminuído de 2001-2009, as taxas no grupo tuberculose sem aids permaneceram estagnadas. Melhorias no diagnóstico e no tratamento são necessárias para a redução da mortalidade entre pacientes com tuberculose em Campinas.

Inequalities in HAART uptake and differential survival according to exposure category in Rio de Janeiro, Brazil.

Despite substantial improvement in prognosis and quality of life among people living with HIV/AIDS (PLWHA) in Brazil, inequalities in access to treatment remain. We assessed the impact of these inequalities on survival in Rio de Janeiro over a 12-year period (2000/11). Data were merged from four databases that comprise the national AIDS monitoring system: SINAN-AIDS (Brazilian Information System for Notificable Diseases; AIDS cases), SISCEL (laboratory tests), SICLOM (electronic dispensing system), and SIM (Brazilian Mortality Information System), using probabilistic linkage. Cox regressions were fitted to assess the impact of HAART (highly active antiretroviral therapy) on AIDS-related mortality among men who have sex with men (MSM), people who inject drugs (PWID), and heterosexuals diagnosed with AIDS, between 2000 and 2011, in the city of Rio de Janeiro, RJ, Brazil. Among 15,420 cases, 60.7% were heterosexuals, 36.1% MSM and 3.2% PWID. There were 2,807 (18.2%) deaths and the median survival time was 6.29. HAART and CD4+ > 200 at baseline were associated with important protective effects. Non-whites had a 33% higher risk of dying in consequence of AIDS than whites. PWID had a 56% higher risk and MSM a 11% lower risk of dying of AIDS than heterosexuals. Non-white individuals, those with less than eight years of formal education, and PWID, were more likely to die of AIDS and less likely to receive HAART. Important inequalities persist in access to treatment, resulting in disparate impacts on mortality among exposure categories. Despite these persistent disparities, mortality decreased significantly during the period for all categories under analysis, and the overall positive impact of HAART on survival has been dramatic.

Risk factors associated with cluster size of Mycobacterium tuberculosis (Mtb) of different RFLP lineages in Brazil.

BACKGROUND: Tuberculosis (TB) transmission is influenced by patient-related risk, environment and bacteriological factors. We determined the risk factors associated with cluster size of IS6110 RFLP based genotypes of Mycobacterium tuberculosis (Mtb) isolates from Vitoria, Espirito Santo, Brazil. METHODS: Cross-sectional study of new TB cases identified in the metropolitan area of Vitoria, Brazil between 2000 and 2010. Mtb isolates were genotyped by the IS6110 RFLP, spoligotyping and RDRio. The isolates were classified according to genotype cluster sizes by three genotyping methods and associated patient epidemiologic characteristics. Regression Model was performed to identify factors associated with cluster size. RESULTS: Among 959 Mtb isolates, 461 (48%) cases had an isolate that belonged to an RFLP cluster, and six clusters with ten or more isolates were identified. Of the isolates spoligotyped, 448 (52%) were classified as LAM and 412 (48%) as non-LAM. Our regression model found that 6-9 isolates/RFLP cluster were more likely belong to the LAM family, having the RDRio genotype and to be smear-positive (adjusted OR = 1.17, 95% CI 1.08-1.26; adjusted OR = 1.25, 95% CI 1.14-1.37; crude OR = 2.68, 95% IC 1.13-6.34; respectively) and living in a Serra city neighborhood decrease the risk of being in the 6-9 isolates/RFLP cluster (adjusted OR = 0.29, 95% CI, 0.10-0.84), than in the others groups. Individuals aged 21 to 30, 31 to 40 and > 50 years were less likely of belonging the 2-5 isolates/RFLP cluster than unique patterns compared to individuals < 20 years of age (adjusted OR = 0.49, 95% CI 0.28-0.85, OR = 0.43 95% CI 0.24-0.77and OR = 0. 49, 95% CI 0.26-0.91), respectively. The extrapulmonary disease was less likely to occur in those infected with strains in the 2-5 isolates/cluster group (adjustment OR = 0.45, 95% CI 0.24-0.85) than unique patterns. CONCLUSIONS: We found that a large proportion of new TB infections in Vitoria is caused by prevalent Mtb genotypes belonging to the LAM family and RDRio genotypes. Such information demonstrates that some genotypes are more likely to cause recent transmission. Targeting interventions such as screening in specific areas and social risk groups, should be a priority for reducing transmission.

Inequalities in HAART uptake and differential survival according to exposure category in Rio de Janeiro, Brazil / Desigualdades no acesso à HAART e diferenças de sobrevida de acordo com a categoria de exposição ao HIV no Rio de Janeiro, Brasil / Desigualdades en el consumo de la TARGA y supervivencia diferencial según la categoría de exposición en Río de Janeiro, Brasil

Abstract: Despite substantial improvement in prognosis and quality of life among people living with HIV/AIDS (PLWHA) in Brazil, inequalities in access to treatment remain. We assessed the impact of these inequalities on survival in Rio de Janeiro over a 12-year period (2000/11). Data were merged from four databases that comprise the national AIDS monitoring system: SINAN-AIDS (Brazilian Information System for Notificable Diseases; AIDS cases), SISCEL (laboratory tests), SICLOM (electronic dispensing system), and SIM (Brazilian Mortality Information System), using probabilistic linkage. Cox regressions were fitted to assess the impact of HAART (highly active antiretroviral therapy) on AIDS-related mortality among men who have sex with men (MSM), people who inject drugs (PWID), and heterosexuals diagnosed with AIDS, between 2000 and 2011, in the city of Rio de Janeiro, RJ, Brazil. Among 15,420 cases, 60.7% were heterosexuals, 36.1% MSM and 3.2% PWID. There were 2,807 (18.2%) deaths and the median survival time was 6.29. HAART and CD4+ > 200 at baseline were associated with important protective effects. Non-whites had a 33% higher risk of dying in consequence of AIDS than whites. PWID had a 56% higher risk and MSM a 11% lower risk of dying of AIDS than heterosexuals. Non-white individuals, those with less than eight years of formal education, and PWID, were more likely to die of AIDS and less likely to receive HAART. Important inequalities persist in access to treatment, resulting in disparate impacts on mortality among exposure categories. Despite these persistent disparities, mortality decreased significantly during the period for all categories under analysis, and the overall positive impact of HAART on survival has been dramatic.

Resumo: Apesar de uma melhora substancial no prognóstico e na qualidade de vida de pessoas vivendo com HIV/aids (PVHA) no Brasil, permanecem desigualdades no acesso ao tratamento. Avaliamos o impacto dessas desigualdades na sobrevida na cidade do Rio de Janeiro ao longo de 12 anos (2000/11). Os dados foram consolidados a partir de quatro bases que constituem o sistema nacional de monitoramento da aids: SINAN-aids (Sistema de Informação de Agravos de Notificação; casos de aids), SISCEL (exames laboratoriais), SICLOM (controle logístico de medicamentos) e SIM (Sistema de Informações sobre Mortalidade), usando relacionamento probabilístico. As regressões de Cox foram ajustadas para avaliar o impacto da HAART (terapia antirretroviral altivamente ativa) na mortalidade relacionada à aids entre homens que fazem sexo com homens (HSH), usuários de drogas injetáveis (UDI) e heterossexuais diagnosticados com aids entre 2000 e 2011 na cidade do Rio de Janeiro. Dos 15.420 casos, 60,7% eram heterossexuais, 36,1% HSH e 3,2% UDI. Houve 2.807 óbitos (18,2%) e a sobrevida mediana foi 6,29 anos. Houve associação significativa entre HAART e contagem de CD4+ > 200 na linha de base e importantes efeitos protetores. Comparados aos brancos, os não-brancos tiveram um risco 33% maior de morrer de aids. Os UDI tiveram um risco 56% maior, enquanto HSH tiveram um risco 11% menor de morrer de aids, comparados aos heterossexuais. Os indivíduos não-brancos, aqueles com menos de oito anos de escolaridade e UDI mostraram probabilidade mais alta de não receber HAART e de morrer de aids. No Rio de Janeiro, persistem desigualdades importantes no acesso ao tratamento, que resultam em impactos diferenciados na mortalidade de acordo com as categorias de exposição. Apesar da persistência dessas disparidades, a mortalidade diminuiu significativamente ao longo do período em todas as categorias analisadas, e o acesso à HAART teve impacto dramático no tempo de sobrevida.

Resumen: Pese a la mejora sustancial en el pronóstico y calidad de vida entre las personas que viven con VIH/SIDA (PLWHA) en Brasil, persisten las desigualdades en el acceso al tratamiento. Evaluamos el impacto de estas desigualdades en la supervivencia en Río de Janeiro, durante un período de 12 años (2000/11). Los datos fueron recabados de cuatros bases de datos que comprenden el sistema nacional de monitoreo del SIDA: SINAN-SIDA (Sistema de Información de Agravios de Notificación; casos de SIDA), SISCEL (pruebas de laboratorio), SICLOM (sistema dispensador electrónico), y SIM (Sistema de Información sobre la Mortalidad), usando una vinculación probabilística. Las regresiones de Cox fueron usadas para evaluar el impacto de la TARGA (terapia antirretroviral de gran actividad) en la mortalidad relacionada con el SIDA, entre hombres que tienen sexo con hombres (HSH), individuos que se inyectan drogas por vía intravenosa (PWID por sus siglas en inglés), y heterosexuales diagnosticados con SIDA, entre 2000 y 2011, en la ciudad de Río de Janeiro, RJ, Brasil. Entre 15.420 casos, un 60,7% eran heterosexuales, un 36,1% HSH y un 3,2% PWID. Hubo 2.807 (18.2%) muertes y el tiempo medio de supervivencia fue 6,29. TARGA y CD4+ > 200 en la base de referencia estuvieron asociados con efectos importantes de protección. Los no-blancos tuvieron un riesgo un 33% mayor de morir a consecuencia de SIDA que los blancos. Los PWID tuvieron un riesgo un 56% mayor, y los HSH un riesgo un 11% menor, de morir de SIDA que los heterosexuales. Los no-blancos, con menos de ocho años de educación formal, y los PWID, eran más propensos a morir de SIDA y menos a recibir TARGA. Existen importantes inequidades en el acceso al tratamiento, resultando en efectos dispares en la mortalidad entre las diferentes categorías exposición. A pesar de estas persistentes disparidades, la mortalidad decreció significativamente durante el periodo para todas las categorías bajo análisis, y el impacto general positivo del TARGA en la supervivencia había sido importantísimo.

Prevalência de sarcoma de Kaposi em pacientes com aids e fatores associados, São Paulo-SP, 2003-2010 / Prevalencia de sarcoma de Kaposi en pacientes con SIDA y factores asociados, São Paulo-SP, Brasil, 2003-2010 / Prevalence of Kaposi's sarcoma in patients with AIDS and associated factors, São Paulo-SP, Brazil, 2003-2010

OBJETIVO: estimar a prevalência de sarcoma de Kaposi (SK) em pacientes com aids e identificar os fatores associados à ocorrência da neoplasia. MÉTODOS: estudo transversal com dados de notificação em dois centros de referência em aids de São Paulo-SP, Brasil, de janeiro/2003 a março/2010; empregaram-se métodos de linkage probabilístico e regressão logística múltipla. RESULTADOS: entre 3.557 casos de aids, 213 (6%) apresentavam SK, 95,3% deles do sexo masculino; associaram-se à ocorrência de SK sexo masculino (OR=3,1; IC95%=1,4;6,6), idade no momento do diagnóstico de aids >28 anos (OR=1,6; IC95%=1,0; 2,6), homens que fazem sexo com homens (OR=3,2; IC95%=2,0;4,9), uso prévio de terapia antirretroviral de alta atividade (HAART) (OR=0,4; IC95%=0,3;0,5), período de diagnóstico de aids de 2007-2010 (OR=0,3; IC95%=0,2;0,4) e contagem de linfócitos T CD4+ <200cel/mm³ (OR=16,0; IC95%=6,0;42,7) e 200-500cel/mm³ (OR=2,5; IC95%=1,1;6,4). CONCLUSÃO: o SK tem alta prevalência em São Paulo-SP; estratégias para o diagnóstico precoce do HIV podem resultar em diminuição desta prevalência.

OBJETIVO: estimar la prevalencia del sarcoma de Kaposi (SK) en pacientes con SIDA e identificar los factores asociados. MÉTODOS: estudio transversal para identificar la asociación entre el SK y SIDA en São Paulo-SP, Brasil; los datos se obtuvieron entre enero de 2003 y marzo de 2010 y se analizaron con el método de linkage probabilística y regresión logística múltipla. RESULTADOS: en 3.557 casos de SIDA, la prevalencia de SK fue 6%; entre los 213 casos de SK, el 95,3% eran varones; estuvieron asociados con SK el sexo masculino (OR=3,1; IC95%=1,4;6,6), la edad >28 años (OR=1,6; IC95%=1,01;2,5 2,6), HSH (OR=3,2; IC95%= 2,0;4,9), el uso previo de HAART (OR=0,4; IC95%=0,3;0,5), diagnóstico de SIDA en 2007-2010 (OR=0,3 IC95%=0,2;0,4) y células T CD4+ <200cel/mm3 (OR=16,0; IC95%=6,0;42,7) y 200-500cel/mm³ (OR=2,5 IC95%=1,1;6,4). CONCLUSIÓN: el SK tiene una alta prevalencia en São Paulo-SP; las estrategias para el diagnóstico precoz del VIH pueden reducirlo.

OBJECTIVE: to estimate the prevalence of Kaposi's sarcoma (KS) in patients with AIDS and identify the associated factors to the occurrence of this neoplasm. METHODS: this is a cross-sectional study with notification data from two AIDS reference centers in São Paulo-SP, Brazil, from January, 2003 to March, 2010; probabilistic linkage and multiple logistic regression methods were applied. RESULTS: among 3,557 AIDS cases, 213 (6%) presented KS; 95.3% of them occurred in males; male sex (OR=3.1; 95%CI=1.4;6.6), age at the AIDS diagnosis >28 years old (OR=1.6; 95%CI=1.0;2.6), MSM (OR=3.2; 95%CI=2.0;4.9), prior use of HAART (OR=0.4; 95%CI=0.3;0.5), AIDS diagnosis between 2007-2010 (OR=0.3; 95%CI=0.2;0.4), and CD4+ T-cell counting under 200cells/mm3 (OR=16.0; 95%CI=6.0;42.7) and 200-500cells/mm³ (OR=2,5; 95%CI=1.1;6.4) were associated to the occurrence of KS. CONCLUSION: KS has a high prevalence in São Paulo-SP; strategies for early HIV diagnosis may reduce this prevalence.

Prevalence of Kaposi's sarcoma in patients with AIDS and associated factors, São Paulo-SP, Brazil, 2003-2010. / Prevalência de sarcoma de Kaposi em pacientes com aids e fatores associados, São Paulo-SP, 2003-2010.

OBJECTIVE: to estimate the prevalence of Kaposi's sarcoma (KS) in patients with AIDS and identify the associated factors to the occurrence of this neoplasm. METHODS: this is a cross-sectional study with notification data from two AIDS reference centers in São Paulo-SP, Brazil, from January, 2003 to March, 2010; probabilistic linkage and multiple logistic regression methods were applied. RESULTS: among 3,557 AIDS cases, 213 (6%) presented KS; 95.3% of them occurred in males; male sex (OR=3.1; 95%CI=1.4;6.6), age at the AIDS diagnosis >28 years old (OR=1.6; 95%CI=1.0;2.6), MSM (OR=3.2; 95%CI=2.0;4.9), prior use of HAART (OR=0.4; 95%CI=0.3;0.5), AIDS diagnosis between 2007-2010 (OR=0.3; 95%CI=0.2;0.4), and CD4+ T-cell counting under 200cells/mm3 (OR=16.0; 95%CI=6.0;42.7) and 200-500cells/mm³ (OR=2,5; 95%CI=1.1;6.4) were associated to the occurrence of KS. CONCLUSION: KS has a high prevalence in São Paulo-SP; strategies for early HIV diagnosis may reduce this prevalence.

Clinical and epidemiological characteristics associated with unfavorable tuberculosis treatment outcomes in TB-HIV co-infected patients in Brazil: a hierarchical polytomous analysis

Abstract Background: TB patients co-infected with HIV have worse treatment outcomes than non-coinfected patients. How clinical characteristics of TB and socioeconomic characteristics influence these outcomes is poorly understood. Here, we use polytomous regression analysis to identify clinical and epidemiological characteristics associated with unfavorable treatment outcomes among TB-HIV co-infected patients in Brazil. Methods: TB-HIV cases reported in the Brazilian information system (SINAN) between January 1, 2001 and December 31, 2011 were identified and categorized by TB treatment outcome (cure, default, death, and development of MDR TB). We modeled treatment outcome as a function of clinical characteristics of TB and patient socioeconomic characteristics by polytomous regression analysis. For each treatment outcome, we used cure as the reference outcome. Results: Between 2001 and 2011, 990,017 cases of TB were reported in SINAN, of which 93,147 (9.4%) were HIV co-infected. Patients aged 15–19 (OR = 2.86; 95% CI: 2.09–3.91) and 20–39 years old (OR = 2.30; 95% CI: 1.81–2.92) were more likely to default on TB treatment than those aged 0–14 years old. In contrast, patients aged ≥60 years were more likely to die from TB (OR = 2.22; 95% CI: 1.43–3.44) or other causes (OR = 2.86; 95% CI: 2.14–3.83). Black patients were more likely to default on TB treatment (OR = 1.33; 95% CI: 1.22–1.44) and die from TB (OR = 1.50; 95% CI: 1.29–1.74). Finally, alcoholism was associated with all unfavorable outcomes: default (OR = 1.94; 95% CI: 1.73–2.17), death due to TB (OR = 1.46; 95% CI: 1.25–1.71), death due to other causes (OR = 1.38; 95% CI: 1.21–1.57) and MDR-TB (OR = 2.29; 95% CI: 1.46–3.58). Conclusions: Socio-economic vulnerability has a significant effect on treatment outcomes among TB-HIV co-infected patients in Brazil. Enhancing social support, incorporation of alcohol abuse screening and counseling into current TB surveillance programs and targeting interventions to specific age groups are interventions that could improve treatment outcomes.

Clinical and epidemiological characteristics associated with unfavorable tuberculosis treatment outcomes in TB-HIV co-infected patients in Brazil: a hierarchical polytomous analysis.

BACKGROUND: TB patients co-infected with HIV have worse treatment outcomes than non-coinfected patients. How clinical characteristics of TB and socioeconomic characteristics influence these outcomes is poorly understood. Here, we use polytomous regression analysis to identify clinical and epidemiological characteristics associated with unfavorable treatment outcomes among TB-HIV co-infected patients in Brazil. METHODS: TB-HIV cases reported in the Brazilian information system (SINAN) between January 1, 2001 and December 31, 2011 were identified and categorized by TB treatment outcome (cure, default, death, and development of MDR TB). We modeled treatment outcome as a function of clinical characteristics of TB and patient socioeconomic characteristics by polytomous regression analysis. For each treatment outcome, we used cure as the reference outcome. RESULTS: Between 2001 and 2011, 990,017 cases of TB were reported in SINAN, of which 93,147 (9.4%) were HIV co-infected. Patients aged 15-19 (OR=2.86; 95% CI: 2.09-3.91) and 20-39 years old (OR=2.30; 95% CI: 1.81-2.92) were more likely to default on TB treatment than those aged 0-14 years old. In contrast, patients aged ≥60 years were more likely to die from TB (OR=2.22; 95% CI: 1.43-3.44) or other causes (OR=2.86; 95% CI: 2.14-3.83). Black patients were more likely to default on TB treatment (OR=1.33; 95% CI: 1.22-1.44) and die from TB (OR=1.50; 95% CI: 1.29-1.74). Finally, alcoholism was associated with all unfavorable outcomes: default (OR=1.94; 95% CI: 1.73-2.17), death due to TB (OR=1.46; 95% CI: 1.25-1.71), death due to other causes (OR=1.38; 95% CI: 1.21-1.57) and MDR-TB (OR=2.29; 95% CI: 1.46-3.58). CONCLUSIONS: Socio-economic vulnerability has a significant effect on treatment outcomes among TB-HIV co-infected patients in Brazil. Enhancing social support, incorporation of alcohol abuse screening and counseling into current TB surveillance programs and targeting interventions to specific age groups are interventions that could improve treatment outcomes.

Long-term protection from isoniazid preventive therapy for tuberculosis in HIV-infected patients in a medium-burden tuberculosis setting: the TB/HIV in Rio (THRio) study.

BACKGROUND: The duration of protection against tuberculosis provided by isoniazid preventive therapy is not known for human immunodeficiency virus (HIV)-infected individuals living in settings of medium tuberculosis incidence. METHODS: We conducted an individual-level analysis of participants in a cluster-randomized, phased-implementation trial of isoniazid preventive therapy. HIV-infected patients who had positive tuberculin skin tests (TSTs) were followed until tuberculosis diagnosis, death, or administrative censoring. Nelson-Aalen cumulative hazard plots were generated and hazards were compared using the log-rank test. Cox proportional hazards models were fitted to investigate factors associated with tuberculosis diagnosis. RESULTS: Between 2003 and 2009, 1954 patients with a positive TST were studied. Among these, 1601 (82%) initiated isoniazid. Overall tuberculosis incidence was 1.39 per 100 person-years (PY); 0.53 per 100 PY in those who initiated isoniazid and 6.52 per 100 PY for those who did not (adjusted hazard ratio [aHR], 0.17; 95% confidence interval [CI], .11-.25). Receiving antiretroviral therapy at time of a positive TST was associated with a reduced risk of tuberculosis (aHR, 0.69; 95% CI, .48-1.00). Nelson-Aalen plots of tuberculosis incidence showed a constant risk, with no acceleration in 7 years of follow-up for those initiating isoniazid preventive therapy. CONCLUSIONS: Isoniazid preventive therapy significantly reduced tuberculosis risk among HIV-infected patients with a positive TST. In a medium-prevalence setting, 6 months of isoniazid in HIV-infected patients with positive TST reduces tuberculosis risk over 7 years of follow-up, in contrast to results of studies in higher-burden settings in Africa.

Active case finding of tuberculosis (TB) in an emergency room in a region with high prevalence of TB in Brazil.

SETTING: Public hospital emergency room (ER) in Porto Alegre, Brazil, a setting with high prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV) infection. OBJECTIVE: To determine the prevalence of PTB, using a symptom based active case finding (ACF) strategy in the ER of a public hospital in an area with high prevalence of TB and HIV, as well as variables associated with pulmonary TB diagnosis. METHODS: Cross sectional study. All patients ≥ 18 years seeking care at the ER were screened for respiratory symptoms and those with cough ≥ 2 weeks were invited to provide a chest radiograph and two unsupervised samples of sputum for acid-fast bacilli smear and culture. RESULTS: Among 31,267 admissions, 6,273 (20.1%) reported respiratory symptoms; 197 reported cough ≥ 2 weeks, of which pulmonary TB was diagnosed in 30. In multivariate analysis, the variables associated with a pulmonary tuberculosis diagnosis were: age (OR 0.94, 95% CI: 0.92-0.97; p<0.0001), sputum production (OR 0.18, 95% CI 0.06-0.56; p = 0.003), and radiographic findings typical of TB (OR 12.11, 95% CI 4.45-32.93; p<0.0001). CONCLUSIONS: This study identified a high prevalence of pulmonary TB among patients who sought care at the emergency department of a tertiary hospital, emphasizing the importance of regular screening of all comers for active TB in this setting.