Assessment of liver disease by non-invasive methods in perinatally infected Brazilian adolescents and young adults living with Human Immunodeficiency Virus (HIV)

ABSTRACT Introduction: Effective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. Methods: Cross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography-FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. Results: Between August 2014 and March 2017, the study enrolled 97 patients, age 10-27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p= 0.022, Fisher's exact test). Conclusion: Liver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.

Percepções acerca da importância das vacinas e da recusa vacinal numa escola de medicina / Perceptions on the importance of vaccination and vaccine refusal in a medical school

RESUMO Objetivo: Identificar a percepção da importância das vacinas e os riscos da recusa vacinal entre alunos de Medicina e médicos. Métodos: Estudo transversal realizado por meio da aplicação de questionários sobre vacinas, recusa vacinal e suas repercussões acerca da saúde pública e individual. A amostra, de 92 sujeitos, foi selecionada numa escola privada de Medicina: grupo 1 (53 estudantes do primeiro ao quarto ano) e grupo 2 (39 médicos). Os dados colhidos foram tabulados no programa Microsoft Excel e analisados estatisticamente com o teste exato de Fisher. Resultados: Os dois grupos consideram o Programa Nacional de Imunizações confiável e reconhecem a importância das vacinas, mas 64,2% dos estudantes e 38,5% dos médicos desconhecem o número de doenças infecciosas evitáveis pelas vacinas no calendário básico. A maioria dos entrevistados possuía carteira de vacinas, mas nem todos receberam vacina influenza 2015. Conheciam pessoas que recusavam vacinas e/ou recusavam vacinar seus filhos (respectivamente, 54,7 e 43,3% dos estudantes e 59,0 e 41,0% dos médicos). Dos médicos, 48,7% já atenderam pacientes que se recusaram a receber vacinas. Consideram causas de recusa vacinal: medo de eventos adversos, razões filosóficas, religiosas e desconhecimento sobre gravidade e frequência das doenças. Aspectos éticos da recusa vacinal e possibilidades legais de exigir vacinas para crianças não são consenso. Conclusões: Alunos de Medicina e médicos não se vacinam adequadamente, apresentam dúvidas sobre calendário vacinal, segurança das vacinas e recusa vacinal. Melhorar sua capacitação é importante estratégia para manter as coberturas vacinais e abordar a recusa vacinal de forma ética.

ABSTRACT Objective: To identify the perception of medical students and physicians on the importance of vaccination and the risks of vaccine refusal. Methods: Cross-sectional study with application of questionnaires about vaccines, vaccine refusal and its repercussions on public and individual health. A sample of 92 subjects was selected from a private medical school: group 1 (53 students from first to fourth grades) and group 2 (39 physicians). Data collected were tabulated in the Microsoft Excel Program and analyzed by Fisher's exact test. Results: Both groups considered the National Immunization Program reliable and recognized the importance of vaccines, but 64.2% of students and 38.5% of physicians are unaware of the vaccine-preventable infectious diseases in the basic immunization schedule. Most of the interviewees had a personal vaccine registry, but not all had received the 2015 influenza vaccine. Both groups had known people who refused vaccines for themselves or for their children (respectively, 54.7 and 43.3% of students and 59.0 and 41.0% of physicians). The total of 48.7% of physicians had already assisted vaccine refusers. Appointed causes of vaccine refusal were: fear of adverse events, philosophical and religious reasons and lack of knowledge about severity and frequency of diseases. Ethical aspects of vaccine refusal and legal possibilities of vaccine requirements for children are not consensus. Conclusions: Medical students and doctors are not adequately vaccinated and have queries about the vaccination schedule, vaccine safety and vaccine refusal. Improving these professionals' knowledge is an important strategy to maintain vaccine coverage and address vaccine refusal ethically.

Vaccine refusal - what we need to know / Recusa vacinal - que é preciso saber

Abstract Objective: Opposition to vaccines is not a new event, and appeared soon after the introduction of the smallpox vaccine in the late 18th century. The purpose of this review is to educate healthcare professionals about vaccine hesitancy and refusal, its causes and consequences, and make suggestions to address this challenge. Source of data: A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and ScieLo databases from 1980 to the present day, using the terms "vaccine refusal," "vaccine hesitancy," and "vaccine confidence." The publications considered as the most relevant by the author were critically selected. Synthesis of data: The beliefs and arguments of the anti-vaccine movements have remained unchanged in the past two centuries, but new social media has facilitated the dissemination of information against vaccines. Studies on the subject have intensified after 2010, but the author did not retrieve any published studies to quantify this behavior in Brazil. The nomenclature on the subject (vaccine hesitancy) was standardized by the World Health Organization in 2012. Discussions have been carried out on the possible causes of vaccine hesitancy and refusal, as well as on the behavior of families and health professionals. Proposals for interventions to decrease public doubts, clarify myths, and improve confidence in vaccines have been made. Guides for the health care professional to face the problem are emerging. Conclusions: The healthcare professional is a key element to transmit information, resolve doubts and increase confidence in vaccines. They must be prepared to face this new challenge.

Resumo Objetivo: Oposição às vacinas não é evento novo e surgiu logo após a introdução da vacina contra varíola no fim do século XVIII. O objetivo desta revisão é esclarecer os profissionais de saúde sobre hesitação e recusa vacinal, suas causas e consequências e fazer sugestões para enfrentar esse desafio. Fonte dos dados: Foi feita busca abrangente e não sistemática nas bases de dados PubMed, Lilacs e Scielo desde 1980 até o presente, com os termos "recusa vacinal", "hesitação vacinal" e "confiança nas vacinas". Foram selecionadas de forma crítica as publicações avaliadas como mais relevantes pela autora. Síntese dos dados: As crenças e os argumentos dos movimentos antivacinas mantiveram-se inalterados nos dois últimos séculos, mas as novas mídias sociais facilitaram a disseminação das informações contra as vacinas. Os estudos sobre o assunto se intensificaram depois de 2010, mas não foram identificados estudos publicados que permitam quantificar esse comportamento no Brasil. A nomenclatura sobre o tema (hesitação vacinal) foi uniformizada pela Organização Mundial de Saúde em 2012. Pesquisas têm sido feitas sobre as possíveis causas da hesitação e recusa vacinal, e também sobre o comportamento das famílias e dos profissionais da saúde. Propostas de intervenções para diminuir as dúvidas da população, esclarecer mitos e melhorar a confiança nas vacinas têm sido feitas. Guias para o profissional de saúde enfrentar o problema estão surgindo. Conclusões: O profissional de saúde é elemento fundamental para transmitir informações, combater as dúvidas e fortalecer a confiança nas vacinas. Eles devem se preparar para enfrentar esse novo desafio.

Resultados negativos na pesquisa científica: aspectos éticos / Negative results in scientific research: ethical aspects / Resultados negativos en la investigación científica: aspectos éticos

Resumo Resultados nulos, negativos ou inesperados são ocorrências possíveis para pesquisadores em todo o mundo. Não publicar tais resultados representa desperdício de recursos (de tempo, dinheiro e esforços). O objetivo deste estudo foi avaliar, mediante aplicação de questionário, o que estudantes de medicina e médicos pensam sobre a publicação de resultados inesperados ou negativos em pesquisa e discutir os aspectos éticos da questão. As questões foram respondidas por 40 alunos e 30 médicos de uma faculdade privada de medicina. Conclui-se que ainda é pouco discutida e aceita a publicação de resultados negativos ou inesperados, persistindo a crença que publicar tais resultados pode prejudicar a reputação dos pesquisadores. Quase todos os participantes acreditam ser importante a publicação desse tipo de resultados, mas apenas cerca de 60% os publicariam. Torna-se, então, importante e necessário ampliar a discussão sobre o assunto nas escolas médicas para se criar nova mentalidade acadêmica.

Abstract Null, negative or unexpected results are possible occurrences for researchers around the world. Not publishing such results is a waste of resources (time, money, and effort). The objective of this study was to evaluate, through a questionnaire, what medical students and physicians thought about the publication of unexpected or negative results in research and to discuss the ethical aspects of the matter. The questions were answered by 40 students and 30 physicians from a private medical school. It is concluded that the publication of negative or unexpected results is still insufficiently discussed and accepted, perpetuating the belief that publishing such results may harm the researchers' reputation. Almost all participants believe it is important to publish these kind of results, but only about 60% of them would publish such results. It is therefore important and necessary to broaden the discussion on this subject in medical schools to create a new academic mindset.

Resumen Los resultados nulos, negativos o inesperados son acontecimientos posibles para los investigadores en todo el mundo. No publicar tales resultados representa un desperdicio de recursos (de tiempo, dinero y esfuerzos). El objetivo de este estudio fue evaluar, a través de la aplicación de un cuestionario, qué piensan los estudiantes de medicina y los médicos sobre la publicación de resultados inesperados o negativos en la investigación y discutir los aspectos éticos de la cuestión. 40 alumnos y 30 médicos de una facultad privada de medicina respondieron al cuestionario. Se concluye que aún es poco discutida y aceptada la publicación de resultados negativos o inesperados, persistiendo la creencia de que publicar tales resultados puede perjudicar la reputación de los investigadores. Casi todos los participantes creen que es importante la publicación de este tipo de resultados, pero solo el 60% de ellos los publicaría. Se hace importante y necesario, entonces, ampliar la discusión sobre este tema en las facultades médicas para crear una nueva mentalidad académica.

Bone mineral density and vitamin D concentration: the challenges in taking care of children and adolescents infected with HIV

ABSTRACT Background: The increase in life expectancy for patients living with human immunodeficiency virus (HIV) infection has resulted in health complications related to a chronic disease. Objectives: To evaluate the prevalence of bone mineral density (BMD) alterations and vitamin D concentrations in HIV-infected children and adolescents and to verify the variations in those parameters during a 12-month interval. Methods: A prospective cohort study with a dual period of evaluation was conducted in 57 patients perinatally HIV-infected and one patient with sexual abuse in early infancy. Demographic, anthropometric, pubertal stage, viral load, T CD4+ cell count and antiretroviral therapy were evaluated. Biochemical tests and total body (TB) and lumbar spine (L1-L4) bone density evaluations by dual X-ray absorptiometry (DXA) were performed. Calcium or vitamin D supplements were prescribed if reduction in BMD or deficiency for vitamin D was detected. Results: 58 patients (ages 5.4-18.3 years; 60.3% girls) were included (T0); 55 patients were reevaluated after 12 (±3) months (T1). Low bone mass for chronological age was found in 6/58 (10.4%) and 6/55(10.9%) patients at T0 and at T1, respectively. There was no statistical relationship between z-scores for BMD (BMD z-score) and the variables sex, fracture history, family history of osteoporosis, physical activity and pubertal stage. There was a relation between BMD z-score alterations for TB and HIV viral load at T1 (p = 0.016). There was no association between duration or classes of antiretroviral therapy and bone density. The mean value of vitamin D in T0 was 23.43 ng/mL ± 2.015 and in T1 22.1 ng/mL ± 0.707 and considered insufficient levels for this population. Conclusion: Patients infected with HIV are at risk for BMD alterations and lower vitamin D serum concentrations; both of these variables should be evaluated at routine examinations in order to improve both prevention and therapeutic planning.

Estudantes e Professores da Área da Saúde Conhecem o Programa Mais Médicos? / Familiarity with the More Doctors Program Among Health Sciences Professors and Students

RESUMO Diminuir as iniquidades na assistência à saúde continua sendo um grande desafio para países tanto pobres quanto ricos. No Brasil, o Programa Mais Médicos (PMM) foi instituído pelo governo federal em 2013 com a proposta de formar recursos humanos na área médica para o Sistema Único de Saúde (SUS), diminuir a carência de médicos, reduzir as desigualdades regionais na área da saúde e aprimorar a formação médica, ampliando a inserção do médico em formação nas áreas onde ele possa conhecer melhor a realidade da saúde da população. Considerando que os estudantes da área da saúde estão diretamente envolvidos com as propostas e os desfechos desse programa, o objetivo deste estudo foi avaliar o conhecimento e posicionamento não só dos estudantes, mas também de seus professores sobre o PMM. Um questionário foi aplicado a 106 alunos e 53 professores de uma faculdade privada na área da saúde (Medicina e Odontologia). A taxa de acerto das 25 questões sobre os objetivos e propostas de ação do PMM variou de 38,4% a 50,6%. A maioria dos docentes e alunos de Medicina referiu conhecer o PMM e reconhecia como proposta do programa diminuir a carência de médicos e melhorar a atuação nas políticas públicas de saúde. A proposta de aprimoramento da formação médica, oferta de cursos de Medicina e de vagas para residência médica, entretanto, era desconhecida por mais de 60% dos entrevistados. A contratação de médicos estrangeiros foi erroneamente considerada não só como um dos objetivos do programa, mas também como a ação proposta para atingir seus objetivos. Em conclusão, alunos e professores de instituições da área da saúde, embora sendo atores importantes na estratégia de atingir os objetivos propostos, conhecem pouco o PMM, particularmente nas ações relacionadas ao currículo das escolas e à residência médica. Estimular debates sobre o programa em escolas médicas pode modificar essa situação e favorecer o seu desfecho.

ABSTRACT Tackling unequal access to healthcare is a major challenge in both developed and developing countries. In Brazil, the Programa Mais Médicos (More Doctors Program – PMM) was created by the federal government in 2013 in order to reduce the shortage of doctors, address regional inequalities in healthcare access and improve medical education, expanding doctors’ training in fields where they can better understand the reality of the population’s health. Considering that students in the healthcare field are directly involved with the proposals and outcomes of this program, the objective of this study was to evaluate student knowledge and positioning and also that of their teachers on the PMM. A questionnaire was therefore administered to 106 students and 53 professors at a private medical and dentistry school. The hit rate for the 25 questions on the PMM’s objectives and proposals ranged from 38.4% to 50.6%.The majority recognized the PMM’s aim to reduce the shortage of doctors and improve public policies related to healthcare. The PMM’s aim to improve medical training, increasing the availability of medical courses and medical residencies, proved, however, to be unknown to over 60% of respondents. The hiring of foreign doctors was mistakenly considered not only to be the objective of the program, but also part of the initiatives designed to achieve the program objectives. The conclusion reached is that although university health sciences students and professors serve as important actors in the strategy for achieving the PMM’s goals, they have limited knowledge on the program, particularly in terms of the initiatives related to medical curricula and medical residencies. Discussion on the program could be introduced to medical courses in order to address this situation and improve the program’s outcomes.

Experiences of adolescents seropositive for HIV/AIDS: a qualitative study / Vivências dos adolescentes soropositivos para HIV/Aids: estudo qualitativo

Objective: Explore the meanings attributed by young individuals about "living as an adolescent with HIV" in a group of patients that acquired the infection at birth and the elements involved with the adherence to antiretroviral treatment. Methods: Qualitative study, involving 20 subjects (aged 13-20 years), followed at services specialized in the treatment of pediatric AIDS in São Paulo, Brazil. Semi-structured interviews were carried out of which script consisted of questions about their personal histories, experiences and difficulties they must face while living with HIV/AIDS. Results: Being "normal" and "different" were central issues voiced by the participants. However, a normal life situation is guaranteed by being responsible with one's health, the condition that the diagnosis be kept secret and concerns about HIV transmission and dissemination to a sexual partner. The answers about treatment show that adherence is a dynamic process and involves moments of greater or lesser interest in relation to care for one's health. The adolescents have plans and projects and although HIV is considered a stressor, positive perspectives for the future prevailed. Conclusions: To live as an adolescent with HIV involves subtle dimensions that need to be recognized and legitimized by professionals who follow the trajectory of these young individuals. It is necessary to allow a space in which the adolescents can reflect and find support regarding issues related to the construction of their sexuality and care of one's own body.

Objetivo: Explorar os significados atribuídos pelos jovens a "viver a adolescência com o HIV" em um grupo de pacientes que adquiriu a infecção ao nascimento e os elementos implicados na adesão ao tratamento antirretroviral. Métodos: Pesquisa de natureza qualitativa, com 20 sujeitos (13 a 20 anos), acompanhados em serviços especializados no tratamento da Aids pediátrica em São Paulo, Brasil. Foram feitas entrevistas semidirigidas cujo roteiro foi composto por questões sobre suas histórias pessoais, dificuldades e experiências que enfrentam diante da infecção pelo HIV/Aids. Resultados: Ser "normal" e "diferente" foram questões centrais no discurso dos participantes. Entretanto, a condição de uma vida normal é garantida mediante a responsabilidade com a saúde, a ressalva de que seja mantido o segredo do diagnóstico e as preocupações com a transmissão do vírus e divulgação do HIV ao parceiro sexual. As respostas sobre o tratamento apontam que a adesão é um processo dinâmico e envolve momentos de maior ou menor interesse em relação aos cuidados com a saúde. Os adolescentes têm planos e projetos e, apesar de o HIV ser considerado um agente estressor, prevaleceram perspectivas positivas diante do futuro. Conclusões: Viver a adolescência com o HIV envolve dimensões delicadas, que necessitam ser reconhecidas e legitimadas pelos profissionais que acompanham a trajetória desses jovens. Trata-se de possibilitar um espaço no qual o adolescente possa refletir e encontrar apoio para as questões relacionadas à construção de sua sexualidade e cuidados com seu próprio corpo.

Impaired bone mineral accrual in prepubertal HIV-infected children: a cohort study

ABSTRACT OBJECTIVE: To evaluate bone mass accrual and determine the influence of clinical, anthropometric, dietary and biochemical parameters on bone mass. METHODS: A cohort study including 35 prepubertal HIV-infected children, between 7 and 12 years, attended at a referral center. At time 1 (T1) and time 2 (T2), patients were assessed according to clinical, anthropometric, dietary, biochemical parameters and bone mineral density (BMD). At T2, patients were divided into prepubertal and pubertal. RESULTS: Despite the increase in bone mass absolute values, there was no improvement in lumbar spine BMD (LSBMD) Z-score (p = 0.512) and worsening in total body BMD (TBMD) Z-score (p = 0.040). Pubertal patients (n = 19) showed higher bone mineral content (BMC) (p = 0.001), TBMD (p = 0.006) and LSBMD (p = 0.002) compared to prepubertal patients. After multivariate linear regression analysis, the predictors of bone mass in T1 were age, BMI and HAZ-scores for BMC; BMI Z-score, adequate serum magnesium concentration and dietary calcium intake for TBMD; adequate serum concentration of magnesium, BMI and HAZ-scores for LSBMD. In T2, age, total body fat and lean body mass (kg) for BMC; BMI Z-score and puberty for TBMD; dietary fat intake, BMI Z-score for BMD and puberty for LSBMD. CONCLUSION: HIV-infected children have compromised bone mass and the presence of puberty seems to provide suitability of these parameters. Adequate intake of calcium and fat appears to be protective for proper bone mass accumulation factor, as well as monitoring nutritional status and serum magnesium concentration.

Noncirrhotic portal hypertension in a human immunodeficiency virus (HIV) infected adolescent / Hipertensão portal não cirrótica em adolescente infectado pelo vírus da imunodeficiência humana (HIV)

OBJECTIVE: To alert the pediatrician who is following up HIV-infected patients about the possibility of non-cirrhotic portal hypertension (NCPH) in this period of life, in order to avoid the catastrophic consequences of this disease as bleeding esophageal varices. CASE DESCRIPTION: A 13 years old HIV-infected patient by vertical route was receiving didanosine (ddI) for 12 years. Although the HIV viral load had been undetectable for 12 years, this patient showed gradual decrease of CD4+ T cells, prolonged thrombocytopenia and high alkaline phosphatase. Physical examination detected splenomegaly, which triggered the investigation that led to the diagnosis of severe liver fibrosis by transient elastography, probably due to hepatic toxicity by prolonged use of ddI. COMMENTS: This is the first case of NCPH in HIV-infected adolescent described in Brazil. Although, the NCPH is a rare disease entity in seropositive patients in the pediatric age group, it should be investigated in patients on long-term ddI or presenting clinical and laboratories indicators of portal hypertension, as splenomegaly, thrombocytopenia and increased alkaline phosphatase.

OBJETIVO: Alertar o pediatra sobre a ocorrência de hipertensão portal não cirrótica (HPNC) na faixa etária pediátrica, no sentido de evitar as consequências catastróficas dessa doença, como o sangramento de varizes de esôfago. DESCRIÇÃO DO CASO: Paciente de 13 anos, infectado pelo HIV por via vertical, recebia esquema antirretroviral com didanosina (ddI) havia 12 anos. Apesar do controle adequado da replicação viral, com carga viral do HIV indetectável havia 12 anos, passou a apresentar diminuição gradativa dos linfócitos TCD4+, trombocitopenia prolongada e fosfatase alcalina elevada. O exame físico detectou esplenomegalia, que desencadeou o processo de investigação e culminou no diagnóstico de fibrose hepática acentuada pela elastografia, por provável toxicidade hepática devido ao uso prolongado de ddI. COMENTÁRIOS: Este é o primeiro caso de HPNC em adolescente infectado pelo HIV descrito no Brasil. Embora seja entidade mórbida rara em pacientes soropositivos para o HIV na faixa etária pediátrica, deve ser investigada nos pacientes em uso prolongado de ddI ou que apresentem indicadores clínicos e/ou laboratoriais de hipertensão portal, como esplenomegalia, trombocitopenia e aumento de fosfatase alcalina.

Persistence of hepatitis A virus antibodies after primary immunization and response to revaccination in children and adolescents with perinatal HIV exposure / Persistência de anticorpos contra o vírus da hepatite A após imunização primária e resposta à revacinação em crianças e adolescentes com exposição perinatal ao HIV

OBJECTIVE: To assess possible factors associated with the loss of antibodies to hepatitis A 7 years after the primary immunization in children of HIV-infected mothers and the response to revaccination in patients seronegative for hepatitis A. METHODS: Quantification of HAV antibodies by electrochemiluminescence was performed in 39 adolescents followed up at the Pediatric Aids Clinic of Federal University of São Paulo (Unifesp): 29 HIV-infected (HIV group) (median age: 12.8 years) and 10 HIV-exposed but non-infected (ENI group) (median age: 13.4 years). All of them received two doses of HAV vaccine (Havrix(r)) in 2002. RESULTS: The median age at primary immunization (PI) was 5.4 years for HIV group and 6.5 years for ENI group. All children, from both groups, had antibodies to HAV >20 mIU/mL after PI. Seven years later, the ENI group showed a median concentration of antibodies = 253.5 mIU/mL, while the HIV group = 113.0 mIU/mL (Mann-Whitney test, p=0.085). All ENI group and 23/29 (79.3%) from HIV group mantained HAV antibodies 7 years after PI. The levels of hepatitis A antibodies in the primary vaccination were the only factor independently associated with maintaining these antibodies for 7 years. The group that lost HAV seropositivity was revaccinated and 83.3% (5/6) responded with antibodies >20 mUI/mL. CONCLUSIONS: The antibodies levels acquired in the primary vaccination in the HIV group were the main factor associated with antibodies loss after HAV immunization.

OBJETIVO: Avaliar possíveis fatores associados à perda de anticorpos para o vírus da hepatite A (VHA) sete anos após a imunização primária e resposta à revacinação em crianças nascidas de mães soropositivas para HIV nos pacientes soronegativos para Hepatite A. MÉTODOS: Quantificação de anticorpos para o VHA por meio da eletroquimioluminescência foi feita em 39 adolescentes acompanhados no Ambulatório de Aids Pediátrica da Universidade Federal de São Paulo (Unifesp): 29 infectados pelo HIV e 10 expostos e não infectados (ENI) pelo HIV, com mediana de idade, respectivamente, de 12,8 e 13,4 anos. Todos receberam duas doses da vacina VHA (Havrix(r)) em 2002. RESULTADOS: A mediana da idade na época da imunização primária (IP) era de 5,4 anos para o grupo HIV e 6,5 anos para o grupo ENI. As crianças dos dois grupos apresentaram anticorpos para o VHA > 20 mUI/mL após a IP. Sete anos após, o grupo ENI apresentava mediana de anticorpos = 253,5 mUI/mL e o grupo HIV = 113,0 mUI/mL (Mann-Whitney; p=0,085). Todo grupo ENI e 23/29 (79,3%) do grupo HIV mantiveram anticorpos contra o VHA sete anos após IP. Os níveis de anticorpos para hepatite A na primovacinação foram o único fator independentemente associado à manutenção desses anticorpos decorridos sete anos. O grupo que perdeu soropositividade para VHA foi revacinado e 83,3% (5/6) responderam com anticorpos >20 mUI/mL. CONCLUSÕES: Os níveis de anticorpos obtidos na primovacinação no grupo HIV foram o principal fator associado à perda de anticorpos após imunização VHA.

Body Composition Changes and Predictors of Lipodystrophy in a Cohort of Pre-pubertal HIV- infected Children.

Aim: To evaluate body composition changes in HIV-infected patients and to identify the predictors of lipodystrophy over time. Methods: A cohort study, evaluated over two and a half years (Time 1: T1; Time 2: T2), including prepubertal HIV-infected children of both genders, between 7-12 years of age. Patient’s data such as transmission, use of prophylaxis for vertical HIV transmission, clinical and immunological classification of disease and current antiretroviral therapy were derived from the medical records. At T1, only subjects with pubertal stage 1 were included. Clinical, anthropometric, body composition and biochemical data were assessed. Patients were divided into two groups: with (LD+) and without lipodystrophy (LD-). Results: A total of 40 patients were enrolled, and 35 patients completed the study. Mean (SD) age was 9.6 (1.1) and 11.6 (1.2) years at T1 and T2, respectively. At T2, 16 (45.7%) children remained prepubertal. LD+ group (n = 8) showed a higher prevalence of short stature (p = 0.008) in T1; higher insulin (p = 0.010) and HOMA-IR (p = 0.013) and reduction of triceps skinfold thickness (p = 0.026) at T2. In both times, we observed lower concentrations of HDLc (p = 0.027), higher values of trunk to arm ratio (p = 0.002, p = 0.001) and lower values of limb to trunk ratio (p = 0.001) and gynoid fat (p= 0.001) in LD+ group. At T1, predictors of lipodystrophy were short stature (OR = 46.198, p = 0.019) and limb to trunk ratio (OR = 0.00009, p = 0.011); in T2, waist circumference (OR = 1.199, p = 0.025) and HDLc (OR = 0.835, p = 0.015). Presence of lipodystrophy was determinant of high insulin levels at T2. Conclusion: In a short period, LD+ group had significant changes in body fat distribution and also biochemical alterations associated to lipodystrophy syndrome.

Barriers to control syphilis and HIV vertical transmission in the health care system in the city of Sao Paulo / Entraves no controle da transmissão vertical da sífilis e do HIV no sistema de atenção à saúde do município de São Paulo

OBJECTIVE: The objective of this study was to identify possible barriers to control vertical transmission of syphilis and HIV through the analysis of the orientation process of pregnant women from prenatal care to the obstetric center at an university hospital in Sao Paulo (Reference) and their return (with their exposed babies) for follow-up after hospital discharge (counter-reference). METHODS: It is a retrospective cross-sectional study including interviews with healthcare personnel. Pregnant women with syphilis and/or HIV-infection admitted for labor or miscarriage were identified from August 2006 to August 2007. Routine care for mothers and babies were analyzed. RESULTS: 56 pregnant women were identified: 43 were HIV-infected, 11 had syphilis and two were coinfected (syphilis/HIV); 22 health care professionals were interviewed. Prenatal care was identified in 91.1% of these women: 7/11 (63.6%) with syphilis; 44/45 (97.8%) HIV-infected or coinfected. The reference for delivery was satisfactory for 57.7% of the syphilis-infected women and 97.7% of the HIV-infected ones. The counter-reference was satisfactory for all babies and mothers at hospital discharge, besides the non-adherence to this recommendation. Interviews with health care professionals showed there are better routines for assisting and following-up pregnant women, puerperal women and HIV-infected or exposed babies than for those infected with syphilis. The epidemiological report and surveillance system are also better for HIV-infected patients. CONCLUSION: The difficulties in the reference and counter-reference system of these women and their babies are evident barriers to control the vertical transmission of these infectious diseases. .

OBJETIVO: O objetivo deste estudo foi identificar possíveis entraves ao controle da transmissão vertical da sífilis e HIV através da análise do processo de encaminhamento das gestantes desde os serviços de atendimento pré-natal até o Centro Obstétrico de um hospital universitário, no município de São Paulo (referência), e seu retorno, com seus bebês expostos, após alta hospitalar, para acompanhamento (contrarreferência). MÉTODO: Estudo de corte transversal, retrospectivo, acrescido de entrevistas com profissionais de saúde. Gestantes com sífilis e/ou infecção pelo HIV foram identificadas na admissão para o parto de agosto de 2006 a agosto de 2007. A rotina e o fluxo dos encaminhamentos de mães e recém-nascidos foram analisados. RESULTADOS: Foram identificadas 56 gestantes infectadas: 43 com infecção pelo HIV, 11 com sífilis e duas coinfectadas (sífilis/HIV); 22 profissionais de saúde foram entrevistados. Acompanhamento pré-natal foi feito por 91,1% das mulheres: 7/11 (63,6%) com sífilis; 44/45 (97,8%) infectadas pelo HIV ou coinfectadas. A referência para o parto foi adequada para 57,1% das gestantes com sífilis e 97,7% daquelas infectadas pelo HIV. A contrarreferência foi adequada para todas as gestantes, apesar da não aderência a essa recomendação. Entrevistas com os profissionais de saúde revelaram que as rotinas e o fluxo de encaminhamento das gestantes, puérperas e recém-nascidos estão mais bem estabelecidos para HIV do que para sífilis. A vigilância epidemiológica e notificação também foram mais eficazes para o HIV. CONCLUSÃO: As dificuldades no sistema de referência e contrarreferência dessas mulheres e seus bebês são evidentes entraves ao controle da t...

Assessment of antioxidants status and superoxide dismutase activity in HIV-infected children

Objective: This study aims to assess the nutritional status of selenium, copper and zinc; and also the erythrocyte superoxide dismutase activity of HIV-infected children compared to a control group. Methods: A cross-sectional study was carried out with prepubertal HIV-infected children (n = 51) and their healthy siblings (n = 32). All biochemical measurements including plasma selenium, serum copper levels, serum and erythrocyte zinc levels and erythrocyte super-oxide dismutase activity were evaluated according to dietary, clinical and biochemical parameters. Results: Compared to the control group, the HIV-infected children had lower z-score values for height-for-age (p = 0.0006), higher prevalence of stunting (11.8%) (p = 0.047), lower selenium levels (p = 0.0006) and higher copper levels (p = 0.019). No difference was found concerning superoxide dismutase activity (p > 0.05). The HIV-infected group presented a higher proportion (45.1%) of children with zinc intakes below the estimated average requirement (p = 0.014); however, no association with zinc biochemical parameters was found. Conclusion: HIV-infected children have an inadequate selenium and copper nutritional status, which could influence the progression to AIDS. An adequate micronutrient status could improve the clinical conditions in these patients and minimize free radical production and cellular oxidative stress. .

Revelação diagnóstica do HIV/Aids para crianças: um relato de experiência / Diagnostic disclosure of HIV/Aids to children: an experience report / Revelación diagnóstica del VIH/SIDA para Niños: un testimonio de experiencia

Trata-se de um relato de experiência sobre a condução e manejo do processo de revelação diagnóstica em crianças vivendo com o HIV/Aids, em dois centros de referência localizados no município de São Paulo, Brasil. O modelo utilizado para compartilhar as informações sobre a doença e tratamento à população pediátrica foi iniciado no ano de 2003 e envolve 5 etapas: captação dos pacientes desconhecedores de sua condição sorológica; encaminhamento para avaliação psicológica; entrevistas com os familiares para o planejamento do processo de revelação; abertura diagnóstica e acompanhamento pós-revelação. A experiência tem demonstrado que após o conhecimento da doença as crianças participam e colaboram com o tratamento, os pais sentem-se aliviados e os profissionais ficam à vontade, durante as consultas, para conversarem abertamente com os pequenos pacientes sobre os exames, acompanhamento clínico e tratamento. A descrição detalhada do trabalho desenvolvido poderá auxiliar outros serviços no desenvolvimento de ações para que a prática da revelação diagnóstica possa ser integrada de forma mais efetiva no contexto do cuidado das crianças que vivem com o HIV/Aids...

This is an experience report on the conduct and management of the process of revealing the diagnosis of children living with HIV/AIDS in two leading centers located in São Paulo, Brazil. The model used to share information about the disease and treatment in the pediatric population was initiated in 2003 and involves 5 steps: gathering patients unaware of their HIV status; referrals for psychological assessment; interviews with family members to plan the disclosure process; open diagnostic and monitoring after the disclosure. Experience has shown that after knowledge of the disease, the children participate and cooperate with treatment, parents feel relieved and professionals are comfortable during consults, to talk openly with young patients about the exams, clinical monitoring and treatment. A detailed description of the work may assist other services in developing actions so that the practice of diagnostic disclosure can be more effectively integrated in the context of the care of children living with HIV/AIDS...

Se trata de un testimonio de experiencia acerca de la conducción y manejo del proceso de revelación diagnóstica en niños que conviven con el VIH/SIDA en dos centros de referencia ubicados en el municipio de San Pablo, Brasil. El modelo utilizado para compartir las informaciones acerca de la enfermedad y tratamiento a la población pediátrica ha sido iniciado en el año de 2003 e involucra 05 etapas: captación de los pacientes que desconocen su condición de serología; encaminamiento para evaluación psicológica; entrevistas con los familiares para la planeación del proceso de revelación; apertura diagnóstica y acompañamiento pos revelación. La experiencia ha demostrado que luego del conocimiento de la enfermedad los niños participan y colaboran con el tratamiento, los padres se sienten aliviados y los profesionales se sienten a gusto, durante las consultas, para hablar abiertamente con los pequeños pacientes acerca de los exámenes, del acompañamiento clínico y del tratamiento. La descripción detallada del trabajo desarrollado podrá auxiliar otros servicios en el desarrollo de acciones para que la práctica de la revelación diagnóstica pueda ser integrada de manera más efectiva en el contexto del cuidado de los niños que conviven con el VIH/SIDA...

Body composition and lipodystrophy in prepubertal HIV-infected children

OBJECTIVE: To identify lipodystrophy in prepubertal HIV-infected children using anthropometric parameters and body composition assessment. METHODS: Cross-sectional study including 40 prepubertal HIV-infected children of both genders seen at the Care Center of the Division of Pediatric Infectious Diseases - Universidade Federal de São Paulo, São Paulo city, Brazil, was carried out from August to December 2008. Age, clinical and immunological status, prophylaxis, transmission and highly active antiretroviral therapy were recorded. Body mass index z-score and height-for-age z-score were calculated to characterize the nutritional status. Circumferences were measured with flexible tape and skinfolds were assessed by an adipometry. Fat mass and lean mass were determined by dual-energy X-ray absorptiometry. Presence of clinical signs of lipodystrophy was assessed by a trained clinician. Data were analyzed using SPSS 12.0 software. RESULTS: The mean age and standard deviation were 9.8 (1.2) years, 50% were girls and 82.5% children from B and C categories. Clinical lipodystrophy and dislypidemia were present in 27.5% and 70%, respectively. The trunk to arm ratio and the limb to trunk ratio had positive association with lipodystrophy. Patients with lipodystrophy had short stature, higher triglycerides values and lower HDL-cholesterol. CONCLUSION: The ratios obtained by skinfolds and dual-energy X-ray absorptiometry measurements can be considered as indicators of preclinical lipodystrophy. The cutoff points have not been determined yet; however, continuous assessment may be useful to identify early body composition changes.

Entrevista com os familiares: um instrumento fundamental no planejamento da revelação diagnóstica do HIV/Aids para crianças e adolescentes / Interviews with family members: a fundamental tool for planning the disclosure of a diagnosis of HIV/aids for children and adolescents

O estudo teve como objetivo apresentar a participação dos cuidadores na construção de estratégias para a comunicação do HIV às crianças soropositivas, assim como, discutir as intervenções que contribuiriam para a superação das dificuldades que comumente impedem os familiares a aceitarem esse processo. Participaram 23 cuidadores de 18 pacientes com indicação para revelação diagnóstica, acompanhados em dois serviços de Aids pediátrica no município de São Paulo, Brasil. Trata-se de pesquisa qualitativa e os dados foram coletados através de entrevistas semidirigidas. Os resultados demonstraram que legitimar os motivos pelos quais os cuidadores relutam em divulgar o diagnóstico às suas crianças, assim como suas motivações, são intervenções que contribuem para diluir resistências, facilitando a aceitação da revelação. A colaboração dos responsáveis forneceu subsídios valiosos para o direcionamento do processo de revelação diagnóstica, além de ter possibilitado o estabelecimento de um vínculo receptivo e favorável, capaz de minimizar inibições que poderiam ser prejudiciais à continuidade do processo.

The scope of this study was to present the participation of caregivers in creating strategies for disclosure of their condition to HIV-positive children, as well as discussing the interventions that might contribute to overcoming the difficulties that commonly prevent family members from accepting this process. The participants included 23 caregivers of 18 patients referred for diagnosis disclosure, monitored at two pediatric AIDS units in the municipality of São Paulo, Brazil. This is a qualitative study and data were collected through semi-structured interviews. The results showed that legitimating reasons why caregivers are reluctant to disclose the diagnosis to the children, as well as their motivations, are interventions that contribute to reduce resistance, facilitating the acceptance of disclosure. The collaboration of caregivers has provided valuable insights for conducting the work, and has enabled the establishment of a receptive and supportive relationship minimizing inhibitions that could be harmful to the continuity of the process.

Descriptive study of HTLV infection in a population of pregnant women from the state of Pará, Northern Brazil / Estudo descritivo da infecção pelo HTLV em uma população de gestantes do Estado do Pará, norte do Brasil

INTRODUCTION: In Brazil, studies have shown that HTLV seroprevalence among pregnant women varies from 0 to 1.8%. However, this seroprevalence was unknown in the State of Pará, Brazil. The present study describes, for the first time, the HTLV seroprevalence among pregnant women from the State of Pará, Northern Brazil. METHODS: 13,382 pregnant women were submitted to HTLV screening during prenatal care, and those with non-seronegative results to anti-HTLV were submitted to Western blot (WB) test to confirm and separate HTLV-1 and HTLV-2 carriers. RESULTS: HTLV seroprevalence in the population of pregnant women was 0.3%, and HTLV-1 was identified in 95.3% of patients. The demographic profile of HTLV carriers was as follows: women with age between 20 and 40 years old (78.4%); residing in the metropolitan region of Belém, Pará (67.6%); and with educational level of high school (56.8%). Other variables related to infection were as follows: beginning of sexual intercourse between the age of 12 and 18 years old (64.9%) and have being breastfed for more than 6 months (51.4%). Most of the women studied had at least two previous pregnancies (35.1%) and no abortion (70.3%). Coinfections (syphilis and HIV) were found in 10.8% (4/37) of these pregnant women. CONCLUSIONS: Seroprevalence of HTLV infection in pregnant women assisted in basic health units from the State of Pará, Northern Brazil, was 0.3% similar to those described in other Brazilian studies. The variables related to infection were important indicators in identifying pregnant women with a higher tendency to HTLV seropositivity, being a strategy for disease control and prevention, avoiding vertical transmission.

INTRODUÇÃO: No Brasil, estudos mostram que a soroprevalência do HTLV entre gestantes varia de 0 a 1,8%. Contudo, esta soroprevalência era desconhecida no Estado do Pará, Brasil. O presente estudo descreve, pela primeira vez, a soroprevalência do HTLV entre gestantes do Estado do Pará, Norte do Brasil. MÉTODOS: 13,382 gestantes foram submetidas à triagem para HTLV durante o pré-natal, e aquelas com sorologia alterada para anti-HTLV foram submetidas ao teste de Western Blot (WB), para confirmar e discriminar portadoras do HTLV-1 e do HTLV-2. RESULTADOS: A soroprevalência do HTLV na população de gestantes foi de 0,3%, sendo o HTLV-1 identificado em 95,3% das pacientes. O perfil demográfico das portadoras do HTLV foi de: mulheres com idade entre 20-40 anos (78,4%); residentes na região metropolitana de Belém (67,6%) e com nível educacional igual ao ensino médio (56,8%). Outras variáveis relacionadas à infecção foram: início das relações sexuais compreendido entre 12-18 anos (64,9%), e ter sido aleitada mais de 6 meses (51,4%). A maior parte das mulheres estudadas teve ao menos duas gestações anteriores (35,1%); e nenhum aborto (70,3%). Co-infecções (sífilis e HIV) foram descritas em 10,8% (4/37) das gestantes. A soroprevalência da infecção pelo HTLV em gestantes atendidas em Unidades Básicas de Saúde do Estado do Pará, Norte do Brasil foi de 0,3% semelhante à descrita em outros estudos brasileiros. As variáveis relacionadas com a infecção são indicadores importantes na identificação de gestantes com maior tendência a soropositividade pelo HTLV, sendo uma estratégia de controle e prevenção, evitando a transmissão vertical.

Human polyomaviruses JC and BK in the urine of Brazilian children and adolescents vertically infected by HIV

The aim of this study was to characterize the urinary excretion of the BK (BKV) and JC (JCV) human polyomaviruses in a cohort of human immunodeficiency virus (HIV)-infected children and adolescents. One hundred and fifty-six patients were enrolled: Group I included 116 HIV-infected children and adolescents [median age = 11.4 years (y); range 1-22 y]; Group II included 40 non-HIV-infected healthy controls (median age = 11.37 y; range 7-16 y). Single urine samples from both groups were screened for the presence of JCV and BKV DNA by polymerase chain reaction at enrolment. The overall rate of JCV and BKV urinary excretion was found to be 24.4 percent and 40.4 percent, respectively (n = 156). Group I had urinary excretion of JCV and BKV in 27.6 percent and 54.3 percent of subjects, respectively. In contrast, Group II showed positive results for JCV in 17.5 percent of subjects and for BKV in 12.5 percent of subjects (p Pearson JCV = 0.20; p Pearson BKV < 0.0001). In Group I, there was no association between JCV/BKV shedding and age, gender or CD4 values. Patients with an HIV viral load < 50 copies/mL had a lower excretion of BKV (p < 0.001) and a trend of lower JCV excretion (p = 0.07). One patient in Group I (1/116, 0.9 percent) showed clinical and radiological features consistent with progressive multifocal leukoencephalopathy, suggesting that children with HIV/polyomavirus coinfection should be kept under surveillance.

HIV-1 drug resistance genotypic profiles in children with undetectable plasma viremia during antiretroviral therapy

Treatment of HIV-1 infection with highly active antiretroviral therapy has led to sustained viral suppression in the plasma in a large number of children. However, studies have suggested that the integrated provirus in resting CD4+ T lymphocytes could be a source of reactivatable virus and maintain drug-resistant virus. We evaluated the resistance-related mutations in children receiving antiretroviral therapy with prolonged viral suppression. Thirty-two peripheral blood mononuclear cell samples from 16 children with viral loads that had been below detection limits for at least 12 months were obtained at two different time points and the DNAs sequenced. The median CD4 cell count was 1,016 cells/mm³ (347-2,588) and 938 cells/mm³ (440-3,038) at the first and second time points, respectively. The median follow-up time was 15 months (9-27). Six (37.5 percent) and seven (43.75 percent) of the 16 patients showed at least one NRTI-associated mutation in the first and second samples, respectively. Two out of 16 (12.5 percent) had an NNRTI-associated mutation at the first time point and three out of 16 (18.75 percent) at the second. In addition, 14 out of 16 (87.5 percent) had at least one PI-associated mutation at both time points. Despite plasma HIV-1 RNA suppression for at least 12 months, resistance-related mutations from previous antiretroviral failures could still be detected in archival virus. Furthermore, viral evolution occurred at the reverse transcriptase region in spite of viral suppression to levels below 400 copies/mL. Persistence of archival resistant virus may be relevant when considering future treatment options.

Improving survival in children with AIDS in Brazil: results of the second national study, 1999-2002 / Ampliação da sobrevida em crianças com AIDS no Brasil: resultados do segundo estudo nacional de 1999 a 2002

The objective of this study is to characterize survival in children with AIDS diagnosed in Brazil between 1999-2002, compared with the first national study (1983-1998). This national retrospective cohort study examined a representative sample of Brazilian children exposed to HIV from mother-to-child transmission and followed through 2007. The survival probability after 60 months was analyzed by sex, year of birth and death, clinical classification, use of antiretroviral therapy (ART) and prophylaxis for opportunistic diseases. 920 children were included. The survival probability increased: comparing cases diagnosed before 1988 with those diagnosed from 2001-2002 it increased by 3.5-fold (from 25 percent to 86.3 percent). Use of ART, initial clinical classification, and final classification were significant (p < 0.001) predictors of survival. Issues regarding quality of records and care were identified. The results point to the success of the Brazilian policy of providing ART. The improvement of clinical status contributes to quality of life, while indicating challenges, particularly practices to improve long-term care.

Este estudo caracteriza a sobrevida em crianças com AIDS no Brasil entre 1999-2002, contextualizando com o primeiro estudo nacional (1983-1998). Trata-se de coorte histórica, com crianças expostas ao HIV por transmissão vertical e acompanhadas até 2007. A probabilidade de sobrevivência em 60 meses foi analisada segundo sexo, ano de nascimento e de óbito, classificação clínica, uso de terapia antirretroviral (TARV) e de profilaxia para doenças oportunistas. No total, 920 crianças foram incluídas. A probabilidade de sobrevivência foi ampliada 3,5 vezes nos dois períodos avaliados, passando de 25 por cento antes de 1988 para 86,3 por cento no período de 2001-2002. Uso de TARV, classificação clínica inicial e atual/final foram preditores que influíram significativamente (p < 0,001) para a ampliação da sobrevida. Os resultados deste estudo indicam o sucesso da política brasileira para a abordagem das crianças infectadas com HIV. A melhora do estado clínico contribuiu para melhora da qualidade de vida, mas sinaliza-se para a necessidade de incorporação de práticas pautadas na integralidade do cuidado.