ABSTRACT Setting: Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH).DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH. Objective: To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers. Design: This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used. Results: The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was: 98% wild genotype and 2% heterozygous. Intronic region: 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes: 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses. Conclusion: Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p = 0.09; OR: 4.57; 95% CI: 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.

RESUMO Este estudo apresenta as principais não conformidades às normas sanitárias encontradas em laboratórios de análises clínicas (LAC) intra-hospitalares públicos localizados no município do Rio de Janeiro (RJ) no período de novembro de 2016 a novembro de 2017. A avaliação de não conformidades sanitárias é fundamental para garantir metas na melhoria do controle da qualidade, aumento da confiabilidade dos resultados gerados e diminuição de riscos em saúde. Por meio da avaliação de 20 laboratórios públicos, federais e municipais, foi possível analisar as principais não conformidades sanitárias nas diferentes fases laboratoriais (pré-analítica, analítica e pós-analítica), avaliando a frequência e a tendência da distribuição através do teste exato de Fisher. Os resultados evidenciaram que 100% dos LAC analisados apresentaram ao menos uma não conformidade; entre aquelas com maiores frequências de não conformidades sanitárias estão as relacionadas com inexistência de procedimentos operacionais padrão (POPs), apresentando 45,5% em LAC de hospitais federais e 66,7% em LAC de hospitais municipais, além de falhas nos processos de limpeza, desinfecção e esterilização, nos equipamentos e na presença do responsável técnico (TM) durante todo o horário de trabalho. As ações de fiscalização sanitária buscam a prestação de serviços em saúde à população que esteja de acordo com padrões de qualidade estabelecidos, ainda que a identificação de não conformidades subsidie a adoção de ações corretivas pelo estabelecimento de saúde.

ABSTRACT The study presents the main nonconformities related to the sanitary regulations found in clinical laboratory analysis (CLA) attached to a public hospital in the city of Rio de Janeiro (RJ) from November 2016 to November 2017. The evaluation of the nonconformities related to sanitary conditions is fundamental to ensure the goals in improving quality control, increasing the reliability of the results generated and reducing health risks. Through the evaluation of 20 federal and municipal public health laboratories, it was possible to analyze the main sanitary nonconformities in the different laboratories phases (pre-analytical, analytical and post-analytical), evaluating, through Fisher's exact test, the frequency and trend distribution of reported nonconformities. One hundred percent (100%) of the clinical analysis laboratories presented at least, one nonconformity. Among those with the highest frequencies of nonconformity related to sanitary conditions are those related to the lack of standard operating procedures (SOPs), presenting 45.5% in clinical analysis laboratories of federal hospitals and 66.7% in clinical analysis laboratories of municipal hospitals. Moreover flaws in the cleaning, disinfection and sterilization processes, in equipments and in the presence of the technical manager (TM) throughout the working hours. Sanitary surveillance actions seek to provide health services to the population that comply with established quality standards, even though the identification of nonconformities subsidizes the adoption of corrective actions by the health establishment.

Toxicity is the most frequently reported reason for modifying or discontinuing the first combined antiretroviral therapy regimens, and it can cause significant morbidity, poor quality of life and also can be an important barrier to adherence, ultimately resulting in treatment failure and viral resistance. Elderly patients with HIV/AIDS (≥50 years) may have a different profile in terms of treatment modification due to higher incidence of comorbidities and polypharmacy. The aim of this study was to describe the incidence of modifying or discontinuing first combined antiretroviral therapy regimen due to toxicity (TOX-MOD) during the first year of treatment at the IPEC – FIOCRUZ HIV/AIDS cohort, Rio de Janeiro, Brazil, stratified by age. Demographic, clinical and treatment characteristics from antiretroviral-naïve patients who first received combined antiretroviral therapy between Jan/1996 and Dec/2010 were collected. Incidence rate and confidence interval of each event were estimated using quasipoisson model. To estimate hazard ratio (HR) of TOX-MOD during the first year of combined antiretroviral therapy Cox's proportional hazards regression was applied. Overall, 1558 patients were included; 957 (61.4%), 420 (27.0%) and 181 (11.6%) were aged <40, 40–49, and ≥50 years, respectively. 239 (15.3%) events that led to any modifying or discontinuing within the first year of treatment were observed; 228 (95.4%) of these were TOX-MOD, corresponding to an incidence rate of 16.6/100 PY (95% CI: 14.6–18.9). The most frequent TOX-MOD during first combined antiretroviral therapy regimen were hematologic (59; 26.3%), central nervous system (47; 20.9%), rash (42; 19.1%) and gastrointestinal (GI) (38; 16.7%). In multivariate analysis, incidence ratio of TOX-MOD during the first year of combined antiretroviral therapy progressively increases with age, albeit not reaching statistical significance. This profile was maintained after adjusting the model for sex, combined antiretroviral therapy regimen and year of combined antiretroviral therapy initiation. These results are important because not only patients are living longer and aging with HIV, but also new diagnoses are being made among the elderly. Prospective studies are needed to evaluate the safety profile of first line combined antiretroviral therapy on elderly individuals, especially in resource-limited countries, where initial regimens are mostly NNRTI-based.