Resumo Introdução: O Protocolo Clínico e Diretrizes Terapêuticas para manejo da infecção pelo HIV em adultos (PCDT) de 2013 recomenda e normatiza início de terapia antirretroviral (TARV) em pacientes com qualquer contagem de LTCD4. O objetivo do estudo foi analisar o primeiro ano de TARV de pacientes em acompanhamento em um centro de referência em HIV/AIDS de Fortaleza, Ceará. Método: O estudo descritivo revisou formulários de solicitação de início e modificação de TARV em pacientes que iniciaram tratamento entre janeiro e julho de 2014. Foram avaliadas todas as mudanças que ocorreram durante o primeiro ano de terapia. Os dados foram analisados no programa Statistical Package for the Social Sciences (SPSS) versão 20. Foram calculados médias, desvios padrão, frequências, testes t Student e Mann-Whitney, com significância de p<0,05. Resultados: Dos 527 pacientes que iniciaram TARV, 16,5% (n=87) realizaram troca no primeiro ano. A maioria era do sexo masculino (59,8%; n=52), de 20 a 39 anos, com apenas uma mudança da TARV (72,4%; n=63). Efavirenz foi o fármaco mais substituído, seguido por tenofovir, zidovudina e lopinavir/ritonavir. O tempo médio de ocorrência das modificações da TARV foi de 120 dias, tendo reações adversas como causas principais. TARV foi efetiva na queda da carga viral desde o 2ºmês de tratamento (p=0,003) e na elevação de LTCD4 desde o 5º mês (p<0,001). Conclusão: Os principais fatores envolvidos em modificações de TARV inicial foram reações adversas, com apenas uma mudança de esquema na maioria dos pacientes. O manejo da TARV estava de acordo com o PCDT de 2013.

Summary Introduction: The Brazilian HIV/AIDS management and treatment guideline (PCDT), published in 2013, recommends and standardizes the use of highly active antiretroviral therapy (HAART) in all adult patients, in spite of LTCD4 count. This study aimed to analyze the first year of HAART use in patients from a reference center on HIV/AIDS management in Fortaleza, Ceará. Method: This descriptive study reviewed all prescription forms of antiretroviral regimens initiation and changes from January to July 2014. All antiretroviral regimen changes that occurred during the first year of therapy were evaluated. Data were analyzed with SPSS version 20. Mean, standard deviation and frequency, Student’s t and Mann-Whitney tests calculations were used, with significance at p<0.05. Results: From 527 patients initiating HAART, 16.5% (n=87) had a regimen change in the first year. These patients were mostly male (59.8%; n=52), aged 20 to 39 years, with only one HAART change (72.4%; n=63). Efavirenz was the most often changed drug, followed by tenofovir, zidovudine and lopinavir/ritonavir. Mean time of HAART changes was 120 days, with adverse reactions as the most prevalent cause. HAART was effective in decreasing viral load since second month of treatment (p=0.003) and increasing LTCD4 lymphocytes since fifth month (p<0.001). Conclusion: The main cause of initial HAART changes was adverse reaction and most patients had only one change in the HAART regimen. HAART prescription was in accordance to the PCDT from 2013.

A anemia falciforme (AF) é uma doença hereditária recessiva caracterizada por anemia hemolítica crônica, inflamação crônica e episódios agudos de hemólise. Hidroxiureia (HU) é amplamente utilizada para aumentar os níveis de hemoglobina fetal (Hb F). O objetivo consiste em padronizar e validar um método para a quantificação de HU no plasma humano utilizando Cromatografia Líquida de Ultra Alta Eficiência (UPLC), a fim de determinar os níveis de HU em pacientes adultos com AF, tratados com HU. Utilizou-se coluna analítica de fase inversa (Nucleosil C18), fase móvel constituída por acetonitrila/água (16,7/83,3). Os tempos de retenção da HU, uréia e metiluréia foram respectivamente de 6,7, 7,7 e 11,4 minutos. Definiram-se todos os parâmetros do processo de validação. Para determinar a precisão e exatidão dos controles de qualidade utilizaram-se concentrações de 100, 740 e 1600 mM de HU no plasma, empregando como padrão interno a metiluréia. A linearidade foi avaliada no intervalo de 50 1600 mM de HU no plasma, obtendo-se coeficiente de correlação de 0,99. O método foi considerado exato e preciso e pode ser realizado com o propósito de determinação quantitativa de HU para monitorização terapêutica de pacientes com AF tratados com esse fármaco.

Sickle cell anemia (SCA) is a recessively inherited disease characterized by chronic hemolytic anemia, chronic inflammation, and acute episodes of hemolysis. Hydroxyurea (HU) is widely used to increase the levels of fetal hemoglobin (HbF). The objective of this study was to standardize and validate a method for the quantification of HU in human plasma by using ultra high performance liquid chromatography (UPLC) in order to determine the plasma HU levels in adult patients with SCA who had been treated with HU. We used an analytical reverse phase column (Nucleosil C18) with a mobile phase consisting of acetonitrile/water (16.7/83.3). The retention times of HU, urea, and methylurea were 6.7, 7.7, and 11.4 min, respectively. All parameters of the validation process were defined. To determine the precision and accuracy of quality controls, HU in plasma was used at concentrations of 100, 740, and 1600 µM, with methylurea as the internal standard. Linearity was assessed in the range of 50-1600 µM HU in plasma, obtaining a correlation coefficient of 0.99. The method was accurate and precise and can be used for the quantitative determination of HU for therapeutic monitoring of patients with SCA treated with HU.

A hidroxiuréia (HU) constitui o avanço mais importante no tratamento da anemia falciforme (AF) por prevenir complicações e aumentar a qualidade de vida dos pacientes. Entretanto, alguns aspectos do tratamento com HU permanecem obscuros, incluindo a sua ação e potencial toxicidade em outras células sanguíneas, tais como neutrófilos. Este estudo utilizou a mensuração da lactato desidrogenase (LDH) e do metil tiazoltetrazólio (MTT) e o ensaio do cometa para investigar a citotoxicidade e índice de dano (ID) ao DNA em neutrófilos de pacientes com AF em uso do medicamento. Nos ensaios de LDH e MTT, observou-se além de ausência de toxicidade, uma ação citoprotetora no grupo de pacientes tratados, Grupo SSHU (n=21, 11 mulheres e 10 homens, com idades entre 19-63 anos), quando comparados aos pacientes sem tratamento, Grupo SS (n=20, 13 mulheres e 07 homens, 18-69 anos), e grupo de indivíduos saudáveis (AA) usado como controle (n=52, 28 mulheres e 24 homens, 19-60 anos), com redução significativa (p<0,001) na atividade de LDH e aumento no percentual de células viáveis pelo MTT (p<0,001). Entretanto, o grupo SSHU apresentou valores de ID significativamente elevados (49,57±6,0 U/A), quando comparados ao grupo AA (7,43 ± 0,94U/A) e grupo SS (22,73 ±5,58 U/A) (p<0,0001), especialmente quando tratados por períodos mais longos (>20 meses), demonstrando que apesar dos efeitos citoprotetores quanto à viabilidade celular, o uso da HU pode induzir lesão ao DNA de neutrófilos.

Hydroxyurea (HU) is the most important advance in the treatment of sickle cell anaemia (SCA) for preventing complications and improving quality of life for patients. However, some aspects of treatment with HU remain unclear, including their effect on and potential toxicity to other blood cells such as neutrophils. This study used the measurement of Lactate Dehydrogenase (LDH) and Methyl ThiazolTetrazolium (MTT) and the comet assay to investigate the cytotoxicity and damage index (DI) of the DNA in the neutrophils of patients with SCA using HU.In the LDH and MTT assays, a cytoprotective effect was observed in the group of patients treated, as well as an absence of toxicity. When compared to patients without the treatment, the SS group (n=20, 13 women and 07 men, aged 18-69 years), and the group of healthy individuals (AA) used as a control group (n=52, 28 women and 24 men, aged 19-60 years), The SSHU group (n=21, 11 women and 10 men, aged 19-63 years) showed a significant reduction (p<0.001) in LDH activity and an increase in the percentage of viable cells by the MTT (p<0.001). However, the SSHU group presented significantly higher DI values (49.57±6.0 U/A) when compared to the AA group (7.43 ± 0,94U/A) and the SS group (22.73 ±5.58 U/A) (p<0.0001), especially when treated for longer periods (>20 months), demonstrating that despite the cytoprotective effects in terms of cell viability, the use of HU can induce DNA damage in neutrophils.

Objective: To investigate the association between kidney dysfunction and haplotypes in sickle cell disease. Methods: A cohort of 84 sickle cell disease patients, treated in a public health service in Fortaleza, Brazil, was studied. Hemoglobin S haplotypes were obtained from 57 patients as they had recently received blood transfusions with 18 of them agreeing to undertake urinary concentrating ability and acidification tests. The glomerular filtration rate was estimated using the Modification of Diet in Renal Disease Study equation. Urinary concentration was evaluated utilizing the urinary and serum osmolality ratio (U/Posm) after 12 hours of water deprivation. Urinary acidification was evaluated by measuring the urinary pH before and after the administration of oral CaCl2. The analysis of the haplotypes of the beta S gene cluster was carried out by polymerase chain reaction-restriction fragment length polymorphism. The analysis of variance (ANOVA) test was used for multiple comparisons of means and the Newman-Keuls test was used to identify which groups were significantly different. Results: The mean age of the patients was 33 ± 13 years with 64.2% being females. The glomerular filtration rate was normal in 25 cases (30%) and a rate > 120 mL/min was seen in 52 cases (62%). Urinary concentration deficit was found in all patients who underwent the test and urinary acidification in 22%. There was no significant difference when comparing patients with the Bantu/Bantu and Benin/Benin haplotypes. On comparing patients with the Central African Republic-haplotype however, a higher number had glomerular filtration rates between 60 and 120 mL/min. Conclusion: There was no significant difference among sickle cell disease patients regarding the haplotypes and kidney dysfunction.

BACKGROUND: Sickle cell disease is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and recurrent vaso-occlusive crises that reduces the quality of life of sufferers. OBJECTIVE: To evaluate the correlation of the levels of lactate dehydrogenase, malonaldehyde and nitrite to fetal hemoglobin in patients with sickle cell disease not under treatment with hydroxyurea in outpatients at a university hospital in Fortaleza, Ceará, Brazil. METHODS: Forty-four patients diagnosed with sickle cell disease were enrolled at baseline. Diagnosis was confirmed by evaluating the beta globin gene using polymerase chain reaction-restriction fragment length polymorphism. The concentration of fetal hemoglobin was obtained by high-performance liquid chromatography. Serum levels of nitrite, malonaldehyde and lactate dehydrogenase were measured by biochemical methods. RESULTS: Significantly higher levels of lactate dehydrogenase, nitrite and malonaldehyde were observed in patients with sickle cell disease compared to a control group. The study of the correlation between fetal hemoglobin levels and these variables showed a negative correlation with nitrite levels. No correlation was found between fetal hemoglobin and malonaldehyde or lactate dehydrogenase. When the study population was stratified according to fetal hemoglobin levels, a decrease in the levels of nitrite was observed with higher levels of fetal hemoglobin (p-value = 0.0415). CONCLUSION: The results show that, similar to fetal hemoglobin levels, the concentration of nitrite can predict the clinical course of the disease, but should not be used alone as a modulator of prognosis in patients with sickle cell disease.

BACKGROUND: Sickle cell anemia is a hemoglobinopathy caused by a mutation that results in the production of an abnormal hemoglobin molecule, hemoglobin S (Hb S). This is responsible for profound physiological changes, such as the sickling of red blood cells. Several studies have shown that hydroxyurea protects against vaso-occlusive crises. OBJECTIVE: The aim of this study was to evaluate the oxidative stress associated with biochemical parameters in patients with sickle cell anemia treated with hydroxyurea. METHODS: The study was conducted with 20 male and 25 female patients at the Hospital Universitário Walter Cantídio. The patients were divided into two groups: a study group (n = 12), patients with sickle cell anemia who were receiving hydroxyurea and a control group (n = 33) of sickle cell anemia patients not submitted to hydroxyurea treatment. The biochemical parameters analyzed were ferritin, transferrin, and serum iron. Glutathione was measured in its reduced form to analyze the oxidative state. RESULTS: The results showed insignificant increases in the levels of serum iron, transferrin and ferritin in patients treated with hydroxyurea when compared with those who did not take the medication. However, the glutathione levels were significantly higher in patients taking hydroxyurea than in controls. CONCLUSION: These results indicate that hydroxyurea possibly acts as an antioxidant by increasing glutathione levels.

RESUMO Objetivo: Determinar os níveis séricos de malonaldeído e de nitrito em pacientes com anemia falciforme em tratamento ou não com hidroxiureia e em acompanhamento ambulatorial. Métodos: Dos 65 pacientes com diagnóstico de anemia falciforme selecionados para o estudo, 51 não fizeram tratamento com hidroxiureia (Grupo 1) e 14 fizeram uso crônico de hidroxiureia (Grupo 2), sendo que 20 indivíduos não tinham hemoglobinopatias (Grupo Controle). Resultados: O Grupo Controle possuía menor e mais homogênea concentração dos níveis de malonaldeído em relação aos outros grupos. Os resultados do Grupo 1 e do Grupo 2 mostraram valores aumentados dos níveis de malonaldeído quando comparados ao Grupo Controle. Quando comparados os valores dos Grupos 1 e 2, não foram observadas alterações significativas nos níveis de malonaldeído. Não houve diferença significativa nos níveis séricos de nitrito entre os grupos. Verificou-se que, no Grupo 2, houve uma correlação estatisticamente significativa dos níveis séricos de malonaldeído com as variáveis clínicas investigadas. Por sua vez, o Grupo 1 mostrou correlação somente com a ocorrência de três ou mais crises vaso-oclusivas. Não se verificou nenhuma correlação nos níveis de nitrito com as variáveis clínicas. Conclusão: Os resultados revelaram que, durante o estabelecimento da patogênese da anemia falciforme, pode ser observado um aumento na peroxidação lipídica. Por outro lado, durante o tratamento com a hidroxureia, não foi detectada nenhuma alteração nos parâmetros oxidativos, provavelmente devido ao curto período de tratamento dos pacientes em estudo.

ABSTRACT Objective: To determine the serum levels of malondialdehyde and nitrite in patients with sickle cell anemia treated or not with hydroxyurea in outpatient's setting. Methods: Of the 65 patients with sickle cell anemia selected for the study, 51 were not treated with hydroxyurea (Group 1), 14 made chronic use of hydroxyurea (Group 2) and 20 individuals had no hemoglobinopathies (Control Group). Results: The Control Group had a lower and more homogeneous concentration of malondialdehyde levels as compared to the other groups. The results of Groups 1 and 2 showed increased values of malondialdehyde levels when compared to the Control Group. Considering the values of Groups 1 and 2, there were no significant changes in the malondialdehyde levels. There was no significant difference in the serum levels of nitrite between the groups. Group 2 presented a statistically significant correlation between serum malondialdehyde levels and the clinical variables investigated. In turn, Group 1 showed correlation only with occurrence of three or more vaso-occlusive crises. There was no correlation between nitrite levels and the clinical variables. Conclusion: The results revealed that during the pathogenesis of sickle cell anemia, an increase in lipid peroxidation was observed. On the other hand, no changes in oxidative parameters were detected during treatment with hydroxyurea, probably due to the short period of treatment of the patients studied.