Effectiveness of screening for tuberculosis in HIV: a pragmatic clinical trial

ABSTRACT OBJECTIVE: To verify the effectiveness of screening for tuberculosis (TB) on all-cause mortality and tuberculosis cases in newly diagnosed HIV-infected patients through a clinical algorithm based on recommendations of the World Health Organization. METHODS: From March 2014 to April 2016, a pragmatic randomized clinical trial was conducted with newly diagnosed and TB-free HIV-infected adults undergoing antiretroviral therapy for up to one month at a major tertiary hospital for HIV in the state of Pernambuco, Brazil. Participants were randomized into intervention and control groups using an automatically-generated random list, and followed-up for at least 6 months. The intervention group was screened for TB at hospital admission and at every follow-up visit through a series of questions addressing TB-related symptoms (cough, fever, night sweating, and weight loss). Patients presenting with any of these symptoms were referred to a pulmonologist and underwent sputum smear microscopy, sputum culture, and rapid molecular testing (GeneXpert). When at least one test result came back positive, TB treatment was initiated. In turn, if patients tested negative but presented with severe clinal symptoms, TB preventive treatment was initiated. Screening for TB was not performed systematically in the control group. The primary outcome assessed in this study was death from all causes, and secondary outcomes included sensitivity and specificity of this screening test, as well as its detection time. RESULTS: This study evaluated 581 patients, 377 in the intervention group (64.9%) and 204 in the control group (35.1%). In total, 36 patients died during the follow-up period. Of these, 26 (6.9%) were from the intervention group, reaching a cumulative mortality coefficient of 69 per 1,000 inhabitants, and 10 (4.9%) from the control group (p = 0.341), with a cumulative mortality coefficient of 49 per 1,000 inhabitants (p = 0.341).

Conhecimento, atitudes e práticas de agentes comunitários de saúde sobre tuberculose pulmonar em uma capital do Nordeste do Brasil / Knowledge, attitudes and practices of community health agents regarding pulmonary tuberculosis in a capital city in northeastern Brazil

Resumo Esse artigo analisa o conhecimento, atitudes e práticas sobre tuberculose de agentes comunitários de saúde (ACS) no Recife, município com altas taxas de incidência e de abandono do tratamento no Brasil. O estudo transversal foi conduzido em uma amostra representativa dos ACS utilizando questionário padronizado. Descreveram-se as frequências das variáveis referentes ao conhecimento, atitudes e práticas e analisou-se a associação do conhecimento satisfatório e práticas adequadas com características dos ACS. Dos 401 ACS elegíveis, 385 (96,0%) foram entrevistados. A maioria era composta por mulheres (87,5%), com idade ≥ 40 anos (66,0%) e desempenhando a função há mais de nove anos (74,5%). Um percentual de 61,7% tinha conhecimento satisfatório e esse conhecimento (75,8%) esteve associado às práticas adequadas (p = 0,008). Quanto às atitudes, 97,1% dos ACS acreditavam estar sob risco de contrair tuberculose e 53,2% atribuíram o risco à função. Parcela significativa dos ACS apresentou conhecimento satisfatório sobre tuberculose e esse conhecimento esteve associado às práticas adequadas. Esse resultado sugere a necessidade de investimentos em ações de capacitação que podem contribuir para a melhoria dos indicadores de tuberculose no município.

Abstract This article analyses the knowledge, attitudes and practices of community health agents (CHAs) regarding tuberculosis in Recife, a municipality with a high incidence of tuberculosis and high treatment dropout rates in Brazil. The cross-sectional study was conducted with a representative sample of CHAs and a standardized questionnaire. The frequencies of the variables related to knowledge, attitudes and practices were described, and the association between satisfactory knowledge and appropriate practices of CHAs was analysed. Of the 401 eligible CHAs, 385 (96.0%) were interviewed. The majority were women (87.5%) aged ≥ 40 years (66.0%) and had been on the job for more than nine years (74.5%). A large percentage (61.7%) had satisfactory knowledge about tuberculosis, and this knowledge (75.8%) was associated with appropriate practices (p = 0.008). Regarding attitudes, 97.1% of CHAs were believed to be at risk of contracting tuberculosis, and 53.2% attributed this risk to their job. The results suggest the need for investment in training actions that may help improve tuberculosis indicators in the municipality.

Factors associated with treatment for latent tuberculosis in persons living with HIV/AIDS / Fatores associados ao tratamento da tuberculose latente em pessoas vivendo com HIV/AIDS / Factores asociados al tratamiento de la tuberculosis latente en personas viviendo con VIH/SIDA

Abstract The aim was to identify factors associated with non-initiation of prophylactic treatment of latent tuberculosis infection (LTBi) in persons living with HIV/AIDS (PLWA), based on a prospective cohort study of PLWA ≥ 18 years of age in two referral services for HIV/AIDS. Of the 232 patients eligible for treatment of LTBi, 69.8% initiated treatment. Following multivariate logistic regression analysis, only treatment in one of the two referral services was associated with non-initiation of treatment for LTBi (p < 0.001). TB incidence in the cohort was 0.6/100 person-years. TB incidence in patients that initiated treatment of LTBi was 0.4/100 person-years, compared to 1.2/100 person-years in those that did not initiate treatment, but the difference was not statistically significant. The study’s most interesting finding was that the main factor associated with the likelihood of treatment for LTBi was the health service where the patient was treated.

Resumo O objetivo foi identificar os fatores associados ao não início do tratamento preventivo para tuberculose (TB) latente (TBLi) em pessoas vivendo com o HIV/AIDS (PVHA). Um estudo de coorte prospectivo foi realizado com PVHA, idade ≥ 18 anos, de dois serviços de referência para HIV/AIDS. De 232 pacientes elegíveis para tratamento da TBLi, 69,8% iniciaram o tratamento. Após análise de regressão logística multivariada, apenas ser tratado em um dos serviços de referência esteve associado ao não início do tratamento para TBLi (p < 0,001). A taxa de incidência de TB na coorte foi de 0,6/100 pessoas/ano. Para os pacientes que iniciaram o tratamento para TBLi, a taxa de incidência de TB foi de 0,4/100 pessoas/ano e para aqueles que não iniciaram, a taxa foi de 1,2/100 pessoas/ano, mas esta diferença não foi estatisticamente significativa. O achado mais interessante deste estudo foi o fato de o principal fator associado ao aumento da probabilidade de ser tratado para TBLi foi a unidade de saúde onde o paciente foi acompanhado.

Resumen El objetivo fue identificar los factores asociados a no iniciar el tratamiento preventivo para la tuberculosis (TB) latente (TBLi) en personas viviendo con VIH/SIDA (PVHA). Un estudio de cohorte prospectivo fue realizado con PVHA, edad ≥ 18 años, de dos servicios de referencia para VIH/SIDA. De 232 pacientes elegibles para el tratamiento de la TBLi, 69,8% iniciaron el tratamiento. Tras el análisis de regresión logística multivariada, simplemente ser tratado en uno de los servicios de referencia estuvo asociado a no comenzar el tratamiento para TBLi (p < 0,001). La tasa de incidencia de TB en la cohorte fue de 0,6/100 personas-año. Para los pacientes que iniciaron el tratamiento para TBLi, la tasa de incidencia de TB fue de 0,4/100 personas-año y para aquellos que no lo iniciaron, la tasa fue de 1,2/100 personas-año, pero esa diferencia no fue estadísticamente significativa. El hallazgo más interesante de este estudio fue el hecho de que el principal factor asociado al aumento de la probabilidad de ser tratado para TBLi fue la unidad de salud donde se realizó el seguimiento del paciente.

Evaluation of four molecular methods for the diagnosis of tuberculosis in pulmonary and blood samples from immunocompromised patients

The present study analysed the concordance among four different molecular diagnostic methods for tuberculosis (TB) in pulmonary and blood samples from immunocompromised patients. A total of 165 blood and 194 sputum samples were collected from 181 human immunodeficiency virus (HIV)-infected patients with upper respiratory complaints, regardless of suspicious for TB. The samples were submitted for smear microscopy, culture and molecular tests: a laboratory-developed conventional polymerase chain reaction (PCR) and real-time quantitative PCR (qPCR) and the Gen-Probe and Detect-TB Ampligenix kits. The samples were handled blindly by all the technicians involved, from sample processing to results analysis. For sputum, the sensitivity and specificity were 100% and 96.7% for qPCR, 81.8% and 94.5% for Gen-Probe and 100% and 66.3% for Detect-TB, respectively. qPCR presented the best concordance with sputum culture [kappa (k) = 0.864)], followed by Gen-Probe (k = 0.682). For blood samples, qPCR showed 100% sensitivity and 92.3% specificity, with a substantial correlation with sputum culture (k = 0.754) and with the qPCR results obtained from sputum of the corresponding patient (k = 0.630). Conventional PCR demonstrated the worst results for sputa and blood, with a sensitivity of 100% vs. 88.9% and a specificity of 46.3% vs. 32%, respectively. Commercial or laboratory-developed molecular assays can overcome the difficulties in the diagnosis of TB in paucibacillary patients using conventional methods available in most laboratories.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4+ lymphocyte count < 200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

Association beteeen smoking, crack cocaine abus and the discontinuation of commbination antiretroviral therapy in recife, pernambuco, Brazil / Associacao entre tabagismo e o uso de crack com a descontinuidade da terapia antirretroviral combinada em Recife, Pernambuco, Brasil

Despite the effectiveness of combination antiretroviral therapy in the treatment of people living with HIV/AIDS (PLWHA), nonadherence to medication has become a major threat to its effectiveness. This study aimed to estimate the prevalence of self-reported irregular use of antiretroviral therapy and the factors associated with such an irregularity in PLWHA. A cross-sectional study of PLWHA who attended two referral centers in the city of Recife, in Northeastern Brazil, between June 2007 and October 2009 was carried out. The study analyzed socioeconomic factors, social service support and personal habits associated with nonadherence to antiretroviral therapy, adjusted by multivariable logistic regression analysis. The prevalence of PLWHA who reported irregular use of combination antiretroviral therapy (cART) was 25.7%. In the final multivariate model, the irregular use of cART was associated with the following variables: being aged less than 40 years (OR = 1.66, 95%-CI: 1.29-2.13), current smokers (OR = 1.76, 95%-CI: 1.31-2.37) or former smokers (OR = 1.43, 95%-CI: 1.05-1.95), and crack cocaine users (OR = 2.79, 95%-CI: 1.24-6.32). Special measures should be directed towards each of the following groups: individuals aged less than 40 years, smokers, former smokers and crack cocaine users. Measures for giving up smoking and crack cocaine should be incorporated into HIV-control programs in order to promote greater adherence to antiretroviral drugs and thus improve the quality of life and prolong life expectancy.

Apesar da eficácia da terapêutica antirretroviral combinada para o tratamento de pessoas vivendo com HIV/Aids, a não adesão aos medicamentos tem se tornado uma das maiores ameaças à efetividade dessa terapêutica. O objetivo desse estudo foi estimar a prevalência de uso irregular autorreferido da terapia antirretroviral e os fatores associados com essa irregularidade em pessoas vivendo com HIV. Foi realizado um estudo seccional de pessoas vivendo com HIV/Aids atendidas em dois centros de referência no Recife, Nordeste do Brasil, entre junho 2007 e outubro de 2009. Foram analisados os fatores socioeconômicos, de apoio social e de hábitos do indivíduo, ajustados através de análise de regressão logística multivariada. A prevalência de pessoas vivendo com HIV/Aids que relataram o uso irregular da terapia antirretroviral combinada (TARC) foi de 25,7%. No modelo multivariado final, o uso irregular da TARC esteve associado às seguintes variáveis: ter menos de 40 anos (OR = 1,66, IC95%: 1,29-2,13), fumantes (OR = 1,76, IC95%: 1,31-2,37) ou ex-fumantes (OR = 1,43, IC95%: 1,05-1,95) e ser usuário de crack (OR = 2,79, IC95%: 1,24-6,32). Medidas especiais devem ser direcionadas para cada um dos seguintes grupos: adultos com menos de 40 anos, fumantes, ex-fumantes e usuários de crack. Ações voltadas para a cessação do tabagismo e do crack devem ser incorporadas ao programa de controle dos infectados pelo HIV, visando promover a maior adesão aos antirretrovirais e, consequentemente, aumentar a expectativa e a qualidade de vida.

Prevalence and socioeconomic factors associated with smoking in people living with HIV by sex, in Recife, Brazil / Prevalencia e fatores socioeconomicos associados com o tabagismo em pessoas vivendo com o HIV por sexo em Recife, Brasil

Introduction: Smoking is the leading cause of preventable death in the world. The prevalence of smoking is higher in people infected with HIV than in the general population. Although it is biologically plausible that smoking increases the morbidity and mortality of people living with HIV/AIDS, few studies in developing countries have analyzed the determinants and consequences of smoking in HIV infected people. Objective: To estimate the prevalence of smoking and identify the socioeconomic factors associated with smoking and smoking cessation in patients with HIV by sex. Methods: A cross-sectional study was conducted with baseline data, obtained from an ongoing prospective cohort study of patients with HIV attending two referral centers in Recife, Northeast Region of Brazil, between July 2007 and October 2009. Results: The prevalence of current smoking was 28.9%. For both sexes, smoking was independently associated with heavy alcohol drinking and marijuana use. Among women, smoking was associated with living alone, not being married and illiteracy; and among men, being 40 years or older, low income and using crack. Compared with ex-smokers, current smokers were younger and more likely to be unmarried, heavy drinkers and marijuana users. Conclusions: It is important to incorporate smoking cessation interventions for the treatment of heavy alcohol drinkers and marijuana users with HIV/AIDS, which may increase life expectancy and quality of life, as smoking is related to risk of death, relapse of tuberculosis, and non communicable diseases. .

Resumo Introdução: Tabagismo é a principal causa de morte evitável no mundo e a sua prevalência é maior em pessoas infectadas pelo HIV. Embora haja plausibilidade biológica no fato de o tabagismo aumentar a morbimortalidade de pessoas que vivem com HIV, poucos estudos em países em desenvolvimento têm analisado os determinantes e as conseqüências desse hábito nessa população. Objetivos: Estimar a prevalência de tabagismo e identificar os fatores associados com o tabagismo e com a cessação do tabagismo em infectados pelo HIV, por sexo. Métodos: Estudo seccional utilizando os dados de base de uma coorte prospectiva de pacientes com HIV atendidos em dois centros de referência em Recife, nordeste do Brasil, entre julho de 2007 e outubro de 2009. Resultados: A prevalência de tabagismo foi de 28,9%. Para ambos os sexos, o tabagismo esteve associado com alcoolismo e uso de maconha. Entre as mulheres, o tabagismo esteve associado com não ser casada, morar só, e não saber ler e escrever; e entre os homens esteve associado com idade ≥ 40 anos, baixa renda mensal e uso de crack. Comparado com os ex-fumantes, os fumantes eram mais jovens, não casados, bebiam mais e fumavam maconha. Conclusão: É importante incorporar intervenções para cessação do tabagismo no tratamento de usuários de maconha e alcoolistas com HIV/AIDS, o que pode aumentar a qualidade e expectativa de vida desses pacientes, uma vez que o tabagismo está relacionado com maior risco de morte, recidiva da tuberculose e também com doenças crônicas não infecciosas. .

Índice de massa corporal em pacientes co-infectados pela tuberculose-HIV em hospital de referência da cidade de Recife, Estado de Pernambuco, Brasil / Body Mass Index of Patients Co-Infected with Tuberculosis and HIV in a Reference Hospital for HIV Patients in the City of Recife, State of Pernambuco, Brazil

O objetivo deste trabalho foi avaliar o índice de massa corporal (IMC) e principais características biológicas, sociais, clínicas e imunológicas de pacientes com tuberculose infectados pelo HIV/aids, comparando-os com aqueles encontrados nos pacientes com HIV/aids sem tuberculose em um hospital de referência para HIV/aids da Cidade de Recife, Estado de Pernambuco, Brasil. Foram selecionados 80 pacientes com HIV/aids, dos quais 40 estavam co-infectados pela tuberculose. Os pacientes foram medidos e pesados, além de responderem a um questionário padronizado elaborado especialmente para a pesquisa. A associação da infecção pelo HIV/aids e tuberculose-doença com IMC inferior a 18,5 kg/m2, indicativo de desnutrição, foi estatisticamente significante. Essa associação poderá ser um sinal sentinela nos serviços de saúde que atendem pacientes infectados pelo HIV, visando proporcionar a eles aporte calórico adequado. Estudos prospectivos dever-se-ão empreender para melhor compreensão da desnutrição como expressão da interação tuberculose-HIV e fator de agravo do quadro clínico de seus pacientes.

The objective of this study was to evaluate the body mass index (BMI) and the main biological, social, clinical and immunological characteristics of patients infected with HIV/AIDS and tuberculosis disease, compared to those HIV infected but with no tuberculosis, in a reference hospital for HIV/AIDS patients in the City of Recife, State of Pernambuco, Brazil. The study population consisted of 80 HIV/AIDS patients, of whom 40 were co-infected with tuberculosis. The patients had their weight and height measured, and answered a structured questionnaire designed specifically for the purpose of the study. The association between a BMI below 18.5 kg/m2 (underweight) and tuberculosis disease-HIV co-infection was statistically significant. That association may be a sentinel sign in health services attended by HIV infected patients, aiming to provide them adequate caloric intake. Prospective studies should be carried out to obtain a better understanding of malnutrition as expression of tuberculosis-HIV co-infection, and as an aggravating factor to clinical conditions of their patients.

Desfecho do tratamento e confirmação laboratorial do diagnóstico de tuberculose em pacientes com HIV/AIDS no Recife, Pernambuco, Brasil / Treatment outcome and laboratory confirmation of tuberculosis diagnosis in patients with HIV/AIDS in Recife, Brazil

OBJETIVO: Comparar a freqüência de desfecho desfavorável (óbito, abandono e falência de tratamento) entre pacientes com co-infecção tuberculose (TB)/HIV submetidos a tratamento para TB com confirmação etiológica do diagnóstico e pacientes co-infectados com TB/HIV e tratados sem confirmação diagnóstica. MÉTODOS: Coorte retrospectivo de pacientes co-infectados com TB/HIV que iniciaram tratamento para TB entre julho de 2002 e junho de 2004, em um serviço de referência para HIV/AIDS no Recife (PE) Brasil. A exposição principal, confirmação laboratorial da TB, foi ajustada pelas variáveis de três blocos: variáveis sócio-demográficas; variáveis relacionadas ao HIV/AIDS; e variáveis relacionadas à TB. Para avaliar a significância estatística dos resultados, utilizaram-se o intervalo de confiança de 95 por cento das odds ratios e o valor de p (teste de qui-quadrado e razão de verossimilhança). RESULTADOS: Foram estudados 262 pacientes. Não se observou associação entre confirmação laboratorial do diagnóstico de TB e desfecho desfavorável, mesmo após o ajuste pelos fatores de confusão. Permaneceram no modelo final da regressão logística múltipla: coexistência de outras doenças oportunistas; contagem de linfócitos CD4 abaixo de 50 células/mm³; carga viral entre 10.000 e 100.000 cópias/mL; dispnéia; forma disseminada de TB; e mudança do tratamento da TB por reação adversa ou intolerância. CONCLUSÕES: Os resultados sugerem que o tratamento para TB sem confirmação etiológica, em pacientes co-infectados, baseado na decisão de profissionais experientes em serviços de referência, não aumentou o risco de desfecho desfavorável do tratamento para TB. Além disso, identificaram-se grupos com maior risco de desfecho desfavorável, os quais devem ser cuidadosamente monitorados.

OBJECTIVE: To compare the frequency of unfavorable outcome (death or default and treatment failure) between tuberculosis (TB)/HIV co-infected patients treated for TB after laboratory confirmation of the diagnosis and TB/HIV co-infected patients who were so treated without diagnostic confirmation. METHODS: A retrospective cohort of TB/HIV co-infected patients who started TB treatment between July of 2002 and June of 2004 at an HIV/AIDS referral center in Recife, Brazil. The main exposure variable, laboratory confirmation of TB, was adjusted for three different sets of variables: sociodemographic variables; HIV/AIDS-related variables; and TB-related variables. In order to evaluate the statistical significance of the results, we calculated odds ratios, with 95 percent confidence intervals, and p values (from chi-square tests and likelihood ratio tests). RESULTS: A total of 262 patients were studied. No association was found between laboratory confirmation of the diagnosis of TB at treatment outset and unfavorable outcome, even after adjustment for confounders. In the final multiple logistic regression model, the following variables remained: the presence of other opportunistic diseases; CD4 lymphocyte count below 50 cells/mm³; viral load between 10,000 and 100,000 copies/mL; dyspnea; the disseminated form of TB; and change in the TB treatment regimen due to adverse reactions or intolerance. CONCLUSIONS: Our results suggest that TB treatment in TB/HIV co-infected patients without etiologic confirmation of TB, at the discretion of experienced physicians in referral centers, did not increase the risk of unfavorable outcomes. In addition, it allowed the identification of groups that should be closely monitored due to a greater risk of unfavorable outcomes.