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

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.

"I was afraid my baby would be upset with me" - women living with HIV's accounts going through non-breastfeeding in São Paulo, Brazil.

In Brazil prevention of mother to child HIV transmission guidelines recommend formula feeding. This qualitative study, carried out in a public clinic (CEADIPE/UNIFESP), aimed at exploring experiences of breastfeeding avoidance of women living with HIV living in São Paulo. Individual interviews were carried out with the support of a semi-structured questionnaire. Data was analyzed in a thematic approach with the support of AtlasTi®. During the months of January-February 2010, 25 women were interviewed, including women with (n = 12) and without previous breastfeeding experience (n = 13). Major themes identified were: Non-breastfeeding as a trigger for stigmatization, Non-breastfeeding, guilt and coping, Attitudes around non-breastfeeding for women with and without previous breastfeeding experience, and Women's support through non-breastfeeding. In conclusion women interviewed faced challenges related to HIV diagnosis, which got entangled with difficulties with breastfeeding avoidance. Different patterns of reaction and coping could be identified, regardless of mothers' previous breastfeeding experiences. Health systems were key in providing women living with HIV with tailored services and the necessary support.

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.

Chronic meningococcemia in a vertically HIV-infected adolescent.

Chronic meningococcemia is a rare manifestation of meningococcal disease, characterized by a period of more than one week of intermittent or continuous fever, arthralgia and skin lesions without meningitis. It can occur both in previously healthy and immunocompromised patients. The gold standard for the diagnosis is culture isolation of Neisseria meningitidis in sterile material. We describe a case of a vertically HIV-infected adolescent with chronic meningococcal disease.

Prolonged Antiretroviral Therapy in Adolescents With Vertical HIV Infection Leads to Different Cytokine Profiles Depending on Viremia Persistence.

BACKGROUND: We investigated immune activation, exhaustion markers and cytokine expression upon stimulation in adolescents with vertical HIV infection. METHODS: Thirty adolescents receiving antiretroviral therapy (ART) for vertical HIV infection, including 12 with detectable viral load (HIV/DET), 18 with undetectable viral load (HIV/UND) and 30 control adolescents without HIV infection (CONTROL), were evaluated for immune activation and programmed cell death protein-1 expression by flow cytometry, and 21 cytokines by Luminex Multiple Analyte Profiling technology after in vitro peripheral blood phytohemagglutinin stimulation. RESULTS: Lower CD4 T cells and higher T cell activation and exhaustion markers were noted on CD4 T and on CD8 T cells and memory subsets from HIV/DET group, who also produced lower in vitro IFN-gamma, IL-10, IL-13, IL-17A, IL-5 and IL-6 than HIV/UND group. HIV/UND were comparable with CONTROL group in respect to CD4 T cell counts and T cell activation and exhaustion markers, but with higher in vitro production of ITAC (a chemokine with leukocyte recruitment function), IL-4 and IL-23. An inverse correlation between cytokine production and programmed cell death protein-1 expression on CD4 T and CD8 T subsets was detected. CONCLUSIONS: Persistent viremia despite ART leads to T cell activation and immune exhaustion with low cytokine production, whereas viral suppression by ART leads to parameters similar to CONTROL, although a different cytokine profile is observed, indicating residual HIV impact despite absence of detectable viremia.

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.

PERCEPTIONS ON THE IMPORTANCE OF VACCINATION AND VACCINE REFUSAL IN A MEDICAL SCHOOL. / PERCEPÇÕES ACERCA DA IMPORTÂNCIA DAS VACINAS E DA RECUSA VACINAL NUMA ESCOLA DE MEDICINA.

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.

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.

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.

Immune response to a Tdap booster in vertically HIV-infected adolescents.

BACKGROUND: Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce. OBJECTIVE: To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL). METHODOLOGY: Thirty HIV adolescents with CD4 cell counts >200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP. RESULTS: Mean age of HIV and CONTROL groups were 17.9 e 17.1 years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28 days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52-32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0-35.5), but lower diphtheria antibodies at 28 days (GMC, 2.3; 95% CI, 0.88-6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3-26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p = .002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-γ) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group. CONCLUSIONS: Both groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.

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.

Vaccine refusal - what we need to know.

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.

Immune response to a Tdap booster in vertically HIV-infected adolescents

Background Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce. Objective To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL). Methodology Thirty HIV adolescents with CD4 cell counts?>200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP. Results Mean age of HIV and CONTROL groups were 17.9 e 17.1?years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28?days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52–32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0–35.5), but lower diphtheria antibodies at 28?days (GMC, 2.3; 95% CI, 0.88–6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3–26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p?=?.002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-?) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group. Conclusions Both groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.

Immune response to a Tdap booster in vertically HIV-infected adolescents

Background Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce. Objective To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL). Methodology Thirty HIV adolescents with CD4 cell counts?>200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP. Results Mean age of HIV and CONTROL groups were 17.9 e 17.1?years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28?days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52–32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0–35.5), but lower diphtheria antibodies at 28?days (GMC, 2.3; 95% CI, 0.88–6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3–26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p?=?.002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-?) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group. Conclusions Both groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.

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.

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

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 23.43ng/mL±2.015 and in T1 22.1ng/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.

[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.

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.