ABSTRACT Objective To compare viral suppression in treatment-naïve adults starting antiretroviral therapy with dolutegravir (50mg)- and efavirenz (600mg)-based regimens. Methods We analyzed secondary data from Brazilian health information systems of people living with human immunodeficiency virus who started antiretroviral therapy between 2015 and 2017 in Minas Gerais, Brazil. The outcome was viral suppression, defined as the achievement of the first viral load <50 copies/mL within 12 months after initiating antiretroviral therapy. This outcome was also compared with viral load <1,000 copies/mL and analyzed in two scenarios: intention-to-treat versus per-protocol. Time to viral suppression and adjusted odds ratio accompanied by 95% confidence intervals were estimated. Results Of the 2,599 participants enrolled, 77.5% were men, and the median age was 34 years. In the intention-to-treat analysis, viral suppression was 58.1% for efavirenz and 76.7% for dolutegravir. People living with HIV on dolutegravir-based regimen were more likely to achieve viral suppression (aOR: 2.44; 95%CI: 2.01-2.95) and had a shorter median time to viral suppression (p<0.0001). Antiretroviral therapy initiation within <120 days, baseline CD4⁺T-cells ≥200 cells/mm3, and viral load <100,000 copies/mL had higher odds of viral suppression. According to the per-protocol analysis, viral suppression ≥90% was observed by considering viral load <1,000 copies/mL. Conclusion Our study demonstrated that viral suppression improved after introducing dolutegravir, although the proportion of patients with viral load <50 copies/mL was lower than expected. Improved access to routine viral load examinations and continuous surveillance of the effectiveness of antiretroviral therapy should be considered. treatmentnaïve treatment naïve 50mg mg (50mg) 600mgbased mgbased 600mg based regimens 201 Gerais Brazil 50 <5 copiesmL copies mL 1 1000 000 <1,00 scenarios intentiontotreat intention treat perprotocol. perprotocol per protocol. protocol 95 estimated 2599 2 599 2,59 enrolled 775 77 5 77.5 men 3 years analysis 581 58 58.1 767 76 7 76.7 dolutegravirbased aOR (aOR 2.44 244 44 95%CI 95CI CI 2.012.95 201295 2.01 2.95 01 2.01-2.95 p<0.0001. p00001 p p<0.0001 . 0 0001 (p<0.0001) 120 <12 days CD4⁺Tcells CD4Tcells CDTcells CD4⁺T cells CD4 T CD 200 ≥20 cellsmm3 cellsmm mm3 mm cells/mm3 100000 100 <100,00 90 ≥90 expected considered (50mg 20 < 00 <1,0 9 259 59 2,5 77. 58. 76. 2.4 24 4 012 2.012.9 20129 2.0 295 2.9 2.01-2.9 p0000 p<0.000 (p<0.0001 <1 Tcells CD4T CDT ≥2 cells/mm 10000 10 <100,0 ≥9 <1, 25 2, 2. 2.012. 2012 29 2.01-2. p000 p<0.00 (p<0.000 ≥ <100, 2.012 2.01-2 p00 p<0.0 (p<0.00 <100 2.01- p0 p<0. (p<0.0 <10 p<0 (p<0. p< (p<0 (p< (p

ABSTRACT The incidence and clinical characteristics of NTM diseases in Brazil remain relatively unknown. The present study describes the diagnosis of NTM isolates, the clinical presentation and treatment outcomes. We analyzed NTM isolates in patients of a tertiary hospital in the Southeast region of Brazil, from January 2008 to July 2019. The ATS/IDSA criteria for diagnosis and treatment of these patients was applied. Mycobacterium kansasii were identified in 13/113 (11.5%) patients. In 59/113 (52.2%) patients who met the ATS criteria for disease, 29/59 (49.1%) received treatment, and 22/29 (75.8%) were cured. The major species identified was M. kansasii. The most frequent symptoms among the treated patients were dyspnea and cough, and the proportion of cured patients was high. unknown outcomes 200 2019 ATSIDSA IDSA applied 13113 13 113 13/11 11.5% 115 11 5 (11.5% 59113 59 59/11 52.2% 522 52 2 (52.2% disease 2959 29 29/5 49.1% 491 49 1 (49.1% 2229 22 22/2 75.8% 758 75 8 (75.8% M cough high 20 201 1311 13/1 11.5 (11.5 5911 59/1 52.2 (52.2 295 29/ 49.1 4 (49.1 222 22/ 75.8 7 (75.8 131 13/ 11. (11. 591 59/ 52. (52. 49. (49. 75. (75. (11 (52 (49 (75 (1 (5 (4 (7 (

Resumo Estudo de utilização de medicamento que descreve o controle da talidomida no Brasil e sua utilização em Minas Gerais. Questionário online foi enviado às unidades federativas do Brasil para coleta de dados de distribuição, dispensação, cadastro de usuários e eventos adversos da talidomida. Dados de distribuição (2011-2018) e dispensação (2015-2018) de Minas Gerais foram obtidos pelo sistema de gerenciamento da assistência farmacêutica. Análise de variância e teste de Tukey foram empregados para comparações dos dados. Das 16 unidades federativas participantes, 100% e 50% utilizavam sistema eletrônico para distribuição e dispensação, respectivamente, e cerca de 43% cadastravam usuários. Sistemas de notificação de eventos adversos eram escassos. Houve redução de 44% na distribuição em Minas Gerais no período. A dispensação manteve-se constante (média 0,0004 DDD/1000 hab./dia) e ocorreu principalmente para eritema nodoso hansênico e mieloma múltiplo. O uso off-label (2,2%) foi crescente. A maioria dos usuários era do sexo masculino (idade média 56 anos). Das mulheres, 30% estavam em idade fértil. A vigilância da talidomida é um desafio em saúde pública. Apesar da ampliação do uso e obrigatoriedade de controle, não há padronização em nível nacional e a notificação de eventos adversos é incipiente.

Abstract Drug utilization research to describe the control of thalidomide in Brazil and its use in Minas Gerais state. An online questionnaire was sent to the Brazilian federative units to collect data concerning distribution, dispensation, user registration, and thalidomide adverse events. Distribution (2011-2018) and dispensing (2015-2018) data in Minas Gerais were obtained through the pharmaceutical care management system. Analysis of variance and Tukey test were used for data comparisons. Of the 16 participating federative units, 100% and 50% used electronic distribution and dispensing systems, respectively, and about 43% registered users. Adverse event reporting systems were scarce. A 44% reduction was observed in the distribution in Minas Gerais for the period. Dispensing remained constant (mean 0.0004 DDD/1,000 inhabitants/day) and occurred mainly for erythema nodosum leprosum and multiple myeloma. Off-label use (2.2%) was increasing. Most users were male (mean age 56 years) and thirty percent of women were of childbearing age. Thalidomide surveillance is a public health challenge. Despite the increased use and mandatory control, there is no national standardization, and adverse event reporting is incipient.

Resumo Estudo de utilização de medicamento que descreve o controle da talidomida no Brasil e sua utilização em Minas Gerais. Questionário online foi enviado às unidades federativas do Brasil para coleta de dados de distribuição, dispensação, cadastro de usuários e eventos adversos da talidomida. Dados de distribuição (2011-2018) e dispensação (2015-2018) de Minas Gerais foram obtidos pelo sistema de gerenciamento da assistência farmacêutica. Análise de variância e teste de Tukey foram empregados para comparações dos dados. Das 16 unidades federativas participantes, 100% e 50% utilizavam sistema eletrônico para distribuição e dispensação, respectivamente, e cerca de 43% cadastravam usuários. Sistemas de notificação de eventos adversos eram escassos. Houve redução de 44% na distribuição em Minas Gerais no período. A dispensação manteve-se constante (média 0,0004 DDD/1000 hab./dia) e ocorreu principalmente para eritema nodoso hansênico e mieloma múltiplo. O uso off-label (2,2%) foi crescente. A maioria dos usuários era do sexo masculino (idade média 56 anos). Das mulheres, 30% estavam em idade fértil. A vigilância da talidomida é um desafio em saúde pública. Apesar da ampliação do uso e obrigatoriedade de controle, não há padronização em nível nacional e a notificação de eventos adversos é incipiente.

Abstract Drug utilization research to describe the control of thalidomide in Brazil and its use in Minas Gerais state. An online questionnaire was sent to the Brazilian federative units to collect data concerning distribution, dispensation, user registration, and thalidomide adverse events. Distribution (2011-2018) and dispensing (2015-2018) data in Minas Gerais were obtained through the pharmaceutical care management system. Analysis of variance and Tukey test were used for data comparisons. Of the 16 participating federative units, 100% and 50% used electronic distribution and dispensing systems, respectively, and about 43% registered users. Adverse event reporting systems were scarce. A 44% reduction was observed in the distribution in Minas Gerais for the period. Dispensing remained constant (mean 0.0004 DDD/1,000 inhabitants/day) and occurred mainly for erythema nodosum leprosum and multiple myeloma. Off-label use (2.2%) was increasing. Most users were male (mean age 56 years) and thirty percent of women were of childbearing age. Thalidomide surveillance is a public health challenge. Despite the increased use and mandatory control, there is no national standardization, and adverse event reporting is incipient.

In Brazil, thalidomide is manufactured by a public laboratory, distributed by the Unified Health System (SUS), and regulated by the National Health Surveillance Agency (Anvisa). Despite the concerns regarding the adverse effects of thalidomide, few drug utilization studies have been conducted to describe processes and outcomes related to this drug. The aim of this study was to elucidate the issues related to the utilization and control of thalidomide, and patient safety within the scope of SUS. In this cross-sectional study, we evaluated the articulation between an outpatient dermatology service of a referral hospital in infectology, the manufacturer, and Anvisa. Four data sources were used: i) interviews with health professionals; ii) data from the Customer Service of the manufacturer, iii) data on adverse events reported to Anvisa, and iv) adverse events identified in outpatient service. Most health professionals interviewed knew the major thalidomide-related adverse effects. None of them ever reported adverse events to Anvisa or contacted the Customer Service. For over three years, there were 330 calls concerning thalidomide at Customer Service, 7% of which were related to adverse events. During a period of six years, Anvisa was notified of only 15 adverse events. Health professionals were aware of the adverse events associated with thalidomide, but not the necessity to report them. The low number of notifications recorded by Anvisa and the information obtained from Customer Service show that pharmacovigilance remains incipient. A pharmacovigilance system that integrates all the services associated with thalidomide is required to strengthen this activity within the SUS to improve patient safety.

Abstract INTRODUCTION The first Brazilian HIV treatment recommendation was put forward in 1996, resulting in 12 subsequent guidelines. Several changes were made regarding “when” and “how” to begin treatment. The latest guideline recommends immediate initiation of antiretroviral therapy (ART). This study aimed to describe the evolution of HIV treatment among people living with HIV (PLHIV) who initiated ART between 2004 and 2018 based on the national guideline recommendations concerning T-CD4+ and VL measurements. METHODS A cross-sectional analysis of data of PLHIV aged >18 years, in Minas Gerais who received ART between 2004 and 2018 was conducted. Clinical, therapeutic, and demographic information were obtained from national healthcare databases. The study was divided into four periods: 2004-2007, 2008-2012, 2013-2016, and 2017-2018. Descriptive analyses were performed. RESULTS A total of 60,618 PLHIV initiated ART (67% male and 48% aged 25-39 years), 36% of whom had CD4 counts at ART initiation and 51% documented VL after ART initiation. The median CD4 count ranged from 288 to 373 cells/µL. The median time to ART initiation decreased from 604 to 28 days and was lower among males (p <0.01). The median time from ART initiation to the first VL result decreased from 101 to 62 days over the study period, while the median VL after ART initiation ranged from 2.3 to 1.7 log10 copies/ml. CONCLUSIONS Although our results demonstrated that most recommendations were followed, there seemed to be little impact on CD4 counts and VL testing. This may result in an inadequate evaluation of ART effectiveness.

Abstract INTRODUCTION: Thalidomide, used to treat erythema nodosum leprosum (ENL), is associated with severe adverse events (AEs) and is highly teratogenic. METHODS: A cross-sectional study was conducted on thalidomide-treated patients with ENL. AEs and selected variables were investigated through interviews and assessment of medical records. Odds ratios with 95% confidence intervals were estimated via logistic regression. RESULTS: Peripheral neuropathy symptoms and deep vein thrombosis (DVT) were the most common AEs reported. Although women of reproductive age used contraceptives, <50% of patients reported using condoms. Polypharmacy was associated with all endpoints, except DVT. CONCLUSIONS: Pharmacovigilance is crucial to prevent harmful thalidomide-associated AEs.

RESUMO OBJETIVO Avaliar se a incidência de infecção hospitalar por microrganismo resistente diminuiu após a implementação da medida restritiva da Agência Nacional de Vigilância Sanitária para comercialização de antimicrobianos. MÉTODOS Estudo de coorte histórica de registros de prontuários de pacientes adultos admitidos para internação em um hospital geral e público no período de maio de 2010 a julho de 2011. Foi formada uma coorte com pacientes internados em período anterior à medida restritiva para comercialização de antimicrobianos (Fase I) e uma segunda coorte com pacientes admitidos após a implantação da medida restritiva (Fase II). RESULTADOS O risco instantâneo de infecção hospitalar por microrganismo resistente foi estimado em sete por 1.000 pessoas-tempo (IC95% 0,006–0,008) na Fase I, e quatro por 1.000 pessoas-tempo (IC95% 0,003–0,005) na Fase II do estudo. As diferenças entre as curvas de sobrevida nas diferentes fases do estudo e estratificadas pela faixa etária também foram significativas (p < 0,05). CONCLUSÕES Os resultados sugerem que a implantação da medida restritiva de comercialização de antimicrobianos pela Agência Nacional de Vigilância Sanitária reduziu a incidência de infecção hospitalar por microrganismo resistente.

ABSTRACT OBJECTIVE To assess whether the incidence of hospital infection by a resistant microorganism decreased after the implementation of the restrictive measure of the National Health Surveillance Agency for the commercialization of antimicrobials. METHODS A historical cohort study of medical records of adult patients admitted to a general and public hospital from May 2010 to July 2011. A cohort was formed with patients admitted in the period before the restrictive measure for the commercialization of antimicrobials (Phase I) and a second cohort was formed with patients admitted after the implementation of the restrictive measure (Phase II). RESULTS The instantaneous risk of hospital infection by a resistant microorganism was estimated at seven by 1,000 people-time (95%CI 0.006–0.008) in Phase I, and four by 1,000 people-time (95%CI 0.003–0.005) in Phase II of the study. The differences between the survival curves in the different phases of the study and stratified by age group were also significant (p < 0.05). CONCLUSIONS The results suggest that the implementation of the restrictive measure of the commercialization of antimicrobials by the National Health Surveillance Agency reduced the incidence of hospital infection by a resistant microorganism.

RESUMO OBJETIVO Avaliar se a incidência de infecção hospitalar por microrganismo resistente diminuiu após a implementação da medida restritiva da Agência Nacional de Vigilância Sanitária para comercialização de antimicrobianos. MÉTODOS Estudo de coorte histórica de registros de prontuários de pacientes adultos admitidos para internação em um hospital geral e público no período de maio de 2010 a julho de 2011. Foi formada uma coorte com pacientes internados em período anterior à medida restritiva para comercialização de antimicrobianos (Fase I) e uma segunda coorte com pacientes admitidos após a implantação da medida restritiva (Fase II). RESULTADOS O risco instantâneo de infecção hospitalar por microrganismo resistente foi estimado em sete por 1.000 pessoas-tempo (IC95% 0,006–0,008) na Fase I, e quatro por 1.000 pessoas-tempo (IC95% 0,003–0,005) na Fase II do estudo. As diferenças entre as curvas de sobrevida nas diferentes fases do estudo e estratificadas pela faixa etária também foram significativas (p < 0,05). CONCLUSÕES Os resultados sugerem que a implantação da medida restritiva de comercialização de antimicrobianos pela Agência Nacional de Vigilância Sanitária reduziu a incidência de infecção hospitalar por microrganismo resistente.

ABSTRACT OBJECTIVE To assess whether the incidence of hospital infection by a resistant microorganism decreased after the implementation of the restrictive measure of the National Health Surveillance Agency for the commercialization of antimicrobials. METHODS A historical cohort study of medical records of adult patients admitted to a general and public hospital from May 2010 to July 2011. A cohort was formed with patients admitted in the period before the restrictive measure for the commercialization of antimicrobials (Phase I) and a second cohort was formed with patients admitted after the implementation of the restrictive measure (Phase II). RESULTS The instantaneous risk of hospital infection by a resistant microorganism was estimated at seven by 1,000 people-time (95%CI 0.006–0.008) in Phase I, and four by 1,000 people-time (95%CI 0.003–0.005) in Phase II of the study. The differences between the survival curves in the different phases of the study and stratified by age group were also significant (p < 0.05). CONCLUSIONS The results suggest that the implementation of the restrictive measure of the commercialization of antimicrobials by the National Health Surveillance Agency reduced the incidence of hospital infection by a resistant microorganism.

Abstract INTRODUCTION: Hypertriglyceridemia incidence should be estimated in HIV-infected patients after antiretroviral therapy (ART) initiation. METHODS: We retrospectively analyzed clinical data of HIV-infected adults at 3 public referral centers. Cumulative and person-time incidences were estimated for patients without hypertriglyceridemia. Survival time and hazard ratio (HR) were estimated by Kaplan-Meier analysis and Cox proportional regression, respectively. RESULTS: Cumulative and person-time incidences were 40.4% and 1.4 cases/100 person-months, respectively. The median period for hypertriglyceridemia occurrence was 47 months. Men and patients with switched ART regimens had increased hypertriglyceridemia risk (HR=3.05 and 3.34, respectively). CONCLUSIONS: Hypertriglyceridemia incidence is high in HIV-infected patients undergoing ART.

INTRODUÇÃO: A hepatite crônica B é uma das doenças infecciosas mais frequentes no mundo e constitui um grave problema de saúde pública MÉTODOS: Para avaliar a eficácia dos análogos de núcleosídeo/nucletídeo utilizados no seu tratamento (adefovir dipivoxil, entecavir e telbivudina) foi conduzida uma revisão sistemática de ensaios clínicos randomizados. Foram consultadas, dentre outras, as bases de dados PubMed e LILACS RESULTADOS: Foram selecionados 29 artigos entre os publicados de janeiro/1970 até dezembro/2009 CONCLUSÕES: Todos os análogos de núcleosídeo/nucletídeo apresentam eficácia superior ou similar à lamivudina. O entecavir pode ser indicado para o tratamento da hepatite B crônica como alternativa à lamivudina em pacientes HBeAg positivo e negativo virgens de tratamento, considerando seu baixo potencial de resistência viral. A adição de adefovir à lamivudina apresentou bons resultados em pacientes resistentes à lamivudina. O uso de entecavir e telbivudina nesses pacientes apresenta risco de resistência cruzada. Telbivudina é um dos mais recentes antivirais disponíveis, mas resistência antiviral já documentada representa limitação ao seu uso como opção terapêutica à lamivudina. Eventos adversos aos análogos de núcleosídeo/nucletídeo foram similares em características, gravidade e incidência quando comparados à lamivudina e placebo.

INTRODUCTION: Chronic hepatitis B is one of the most frequent infectious disease in the world and represents a serious problem of public health METHODS: A systematic review of randomized clinical trials was conducted to evaluate the efficacy of the nucleoside/nucleotide analogues (adefovir, entecavir and telbivudine) used for the treatment of chronic hepatitis B. The databases PubMed and LILACS were consulted, among others RESULTS: Twenty nine articles published between January/1970 to December/2009 were selected CONCLUSIONS: All nucleoside/nucleotide analogues demonstrate upper or similar efficacy to lamivudine. The entecavir can be appropriate for patients with chronic hepatitis B, HBeAg positive and negative treatment-naive as alternative to lamivudine, considering its low potential of viral resistance. The addition of adefovir to lamivudine presented good results in lamivudine resistant patients. The use of entecavir and telbivudine in those patients presents risk of crossed resistance. TBV is one of the most recent antivirals available, but antiviral resistance already documented represents limitation to its use as therapeutic option to LAM. Adverse events of nucleoside/nucleotide analogues were similar in characteristics, gravity and incidence when compared to the lamivudina and placebo.