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.

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.

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.

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.

Adolescents growing with HIV/AIDS: experiences of the transition from pediatrics to adult care

Abstract The main objective of this work is to describe the formation of the Transition Adolescent Clinic (TAC) and understand the process of transitioning adolescents with HIV/AIDS from pediatric to adult care, from the vantage point of individuals subjected to this process. A qualitative method and an intentional sample selected by criteria were adopted for this investigation, which was conducted in São Paulo, Brazil. An in-depth semi-structured interview was conducted with sixteen HIV-infected adolescents who had been part of a transitioning protocol. Adolescents expressed the need for more time to become adapted in the transition process. Having grown up under the care of a team of health care providers made many participants have reluctance toward transitioning. Concerns in moving away from their pediatricians and feelings of disruption, abandonment, or rejection were mentioned. Participants also expressed confidence in the pediatric team. At the same time they showed interest in the new team and expected to have close relationships with them. They also ask to have previous contacts with the adult health care team before the transition. Their talks suggest that they require slightly more time, not the time measured in days or months, but the time measured by constitutive experiences capable of building an expectation of future. This study examines the way in which the adolescents feel, and help to transform the health care transition model used at a public university. Listening to the adolescents’ voices is crucial to a better understanding of their needs. They are those who can help the professionals reaching alternatives for a smooth and successful health care transition.

Renal abnormalities in a cohort of HIV-infected children and adolescents.

BACKGROUND: This study aimed to identify the prevalence of renal abnormalities and the evolution of glomerular filtration rate (GFR) among human immunodeficiency virus (HIV)- infected children and adolescents followed up in an infectious disease outpatient pediatric clinic. METHODS: We performed a cohort study of 115 children and adolescents. Outcomes of two evaluations for urinalysis, microalbuminuria/urinary creatinine ratio, urinary retinol-binding protein (uRBP) concentration, and estimated GFR (eGFR) were obtained for each patient, with an average interval of 6 months between evaluations. These changes were correlated with gender, age, race, body mass index (BMI), height-for-age (H/A) percentile, clinical and immunological classification of HIV infection, use of antiretroviral therapy (ART), HIV viral load (VL), and CD4+ T-lymphocyte count. RESULTS: Mean patient age at the time of inclusion in the study was 12.6 ± 3.2 years; 50.4 % were male, 81.7 % had acquired immune defeciency syndrome (AIDS), 80.9 % had CD4+ < 500 cells/mm(3), and 87.8 % were on ART. Urinary changes included hematuria (11.3 %), proteinuria (7 %), and microalbuminuria (11.6 %); uRBP was present in 3.8 %; and mean eGFR was 163 ± 32 ml/min/1.73 m(2). CONCLUSIONS: The subclinical renal abnormalities found in this study may indicate early manifestations of a broad spectrum of renal dysfunction associated with HIV and involves the decision to initiate or modify ART.

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.

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...

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.

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.

Short communication: immunogenicity of an inactivated influenza vaccine and postvaccination influenza surveillance in HIV-infected and noninfected children and adolescents.

Individuals infected with HIV are at higher risk for severe cases of seasonal influenza infection and should receive annual doses of vaccine. Our objectives were to evaluate the immunogenicity of an influenza vaccine in 37 HIV-infected patients (HIV group) compared to 29 uninfected individuals (control group) and to carry out a clinical and virological surveillance of influenza during a 6-month follow-up. Both groups received the vaccine recommended for the southern hemisphere in 2008. Antibody responses to antigens H1N1, H3N2, and B were measured in blood samples at vaccination (T0) and after 1 month (T1). Influenza surveillance was performed by weekly telephone calls for a follow-up period of 6 months. Nasal washes were taken from subjects with respiratory symptoms. The direct immunofluorescence assay in house polymerase chain reaction (PCR) and real-time PCR were used for the detection of different respiratory viruses. The median age of the participants was 13.3 years (sd = 2.2) and 12.1 years (sd = 1.3) for the HIV group and control group, respectively. One month after vaccination (T1), both groups showed significant increases in the antibody geometric mean titers (GMTs) for all antigens. However, healthy controls showed higher values for antigens A/H1N1 and A/H3N2 (p = 0.002 and 0.001, respectively). There was a higher increase in the percentage of HIV-uninfected subjects with protective A/H1N1 antibodies (96.6%) compared to HIV-infected vaccinees (67.6%) at T1 (p = 0.004). Rhinovirus (27.7%) and coronavirus (22.5%) were the most prevalent agents identified in HIV-infected individuals. In the control group, the viruses most frequently found were rhinovirus (24.2%) and adenovirus (21.2%). The seroprotection rate for the H1N1 antigen was higher in the control group, which also showed a greater increase in GMTs for H1N1 and H3N2 antigens after immunization. Viral agents were identified in 39/60 (65%) episodes of respiratory infections from the HIV-infected group and in 17/32 episodes (53.1%) from the control group (p = 0.273).

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.

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% and 40.4%, respectively (n = 156). Group I had urinary excretion of JCV and BKV in 27.6% and 54.3% of subjects, respectively. In contrast, Group II showed positive results for JCV in 17.5% of subjects and for BKV in 12.5% 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%) showed clinical and radiological features consistent with progressive multifocal leukoencephalopathy, suggesting that children with HIV/polyomavirus coinfection should be kept under surveillance.

A transição de adolescentes com HIV/AIDS para a clínica de adultos: um novo desafio / Transitioning adolescents living with HIV/AIDS to adult-oriented health care: an emerging challenge

OBJETIVO: Revisar a literatura sobre transição de adolescentes da pediatria para a clínica de adultos, com enfoque na clínica da AIDS, discutindo o tema no contexto das doenças crônicas. FONTES DOS DADOS: A pesquisa bibliográfica utilizou os bancos de dados MEDLINE e LILACS (1990-2010), selecionando artigos disponíveis em inglês ou francês. SÍNTESE DOS DADOS: A transição de adolescentes com doenças crônicas, sempre atendidos por pediatras, para os serviços de adultos, tem sido uma crescente preocupação nas diversas especialidades pediátricas. Mais recentemente, jovens vivendo com HIV/AIDS estão atingindo essa fase e apresentando diversas dificuldades. Os estudos avaliados nessa revisão discutem alguns tópicos relevantes, como: a diferença entre transferência, um evento isolado, e transição, um processo gradual; os modelos utilizados nos diversos serviços; a importância de a transição ser feita de maneira planejada e individualizada; a necessidade de ampla interação entre as equipes pediátricas e os serviços de adultos; a importância da participação conjunta dos adolescentes, familiares e profissionais de saúde; as barreiras e os fatores que favorecem uma transição bem-sucedida; as necessidades e particularidades dos adolescentes com HIV/AIDS nesse momento importante de mudanças. CONCLUSÕES: Vários autores concordam que a transição de adolescentes para os serviços de adultos deva ser um processo gradual, não determinado apenas pela idade. É preciso um planejamento que envolva adolescentes, familiares e equipe dos serviços pediátricos e de adultos. No entanto, há pouca evidência que privilegie um modelo específico de transição, o que lança o desafio para a realização de mais estudos prospectivos sobre o tema, especialmente em grupos de maior vulnerabilidade, como o de adolescentes vivendo com HIV/AIDS.

OBJECTIVE: To review the literature on transition from pediatric to adult-oriented health care and discuss this issue in the specific context of chronic conditions. SOURCES: MEDLINE and LILACS were searched for relevant English and French-language articles published between 1990 and 2010. SUMMARY OF THE FINDINGS: The transition of adolescents with chronic diseases from pediatric care to adult-oriented services has been a growing concern among pediatric specialties. In recent years, young people living with HIV/AIDS have begun to reach adulthood, giving rise to several challenges. The studies reviewed herein discuss such relevant topics as: the difference between transfer, an isolated event, and transition, a gradual process; the transition models used in different services; the importance of transitioning in a planned and individualized manner; the need for comprehensive interaction between pediatric and adult-oriented care teams; the importance of joint participation of adolescents, their families, and health professionals in the process; barriers to and factors that promote successful transitions; and the special needs of adolescents with HIV/AIDS in this important period of life. CONCLUSIONS: Several authors agree that transitioning adolescents to adult-oriented health care should be a gradual process not determined by age alone. It requires a plan established with ample dialogue among adolescents, their families, and pediatric and adult care teams. However, there is little evidence to support any specific model of health care transition. This should prompt researchers to conduct more prospective studies on the theme, especially in more vulnerable groups such as adolescents living with HIV/AIDS.

Validação e reprodutibilidade de uma escala de auto-eficácia para adesão ao tratamento anti-retroviral em pais ou cuidadores de crianças e adolescentes vivendo com HIV/AIDS / Validity and reliability of a self-efficacy expectancy scale for adherence to antiretroviral therapy for parents and carers of children and adolescents with HIV/AIDS

OBJETIVO: Validar uma escala de auto-eficácia para adesão ao tratamento anti-retroviral em crianças e adolescentes com HIV/AIDS, levando em consideração a perspectiva dos pais/responsáveis, e avaliar a sua reprodutibilidade. MÉTODOS: O estudo foi realizado no Hospital-Dia do Centro de Referência e Treinamento em DST/AIDS de São Paulo. Foram entrevistados os pais/responsáveis de 54 crianças e adolescentes de 6 meses a 20 anos que passaram em consulta de rotina pelo serviço. Os dados de auto-eficácia foram levantados pela escala de auto-eficácia para seguir prescrição anti-retroviral (AE), que foi calculada de duas maneiras: análise fatorial e fórmula já definida. A consistência interna da escala foi verificada pelo coeficiente ade Cronbach. A validade foi avaliada pela comparação das médias dos escores entre grupos de pacientes aderentes e não aderentes ao tratamento anti-retroviral (teste de Mann-Whitney) e cálculo do coeficiente de correlação de Spearman entre os escores e parâmetros clínicos. A reprodutibilidade foi verificada por meio do teste de Wilcoxon, pelo coeficiente de correlação intraclasse (CCI) e pelo gráfico de Bland-Altman. RESULTADOS: A escala de AE apresentou boa consistência interna (a= 0,87) e boa reprodutibilidade (CCI = 0,69 e CCI = 0,75). Quanto à validade, a escala de AE conseguiu discriminar pacientes aderentes e não aderentes ao tratamento anti-retroviral (p = 0,002) e apresentou correlação significativa com a contagem de CD4 (r = 0,28; p = 0,04). CONCLUSÕES: A escala de AE pode ser utilizada para avaliar a adesão à terapia anti-retroviral em crianças e adolescentes com HIV/AIDS, levando em consideração a perspectiva dos pais/cuidadores.

OBJECTIVE: To validate and evaluate the reproducibility of a self-efficacy (SE) scale for adherence to antiretroviral therapy in children and adolescents with HIV/AIDS, taking into account the perspective of parents/guardians. METHODS: The study was carried out at the Hospital-Dia, Centro de Referência e Treinamento em DST/AIDS (CRT/SP), in São Paulo, Brazil. The parents/guardians of 54 children and adolescents aged 6 months to 20 years were interviewed during routine consultations at our service. Data on SE were collected using the Self-Efficacy for Following Anti-Retroviral Prescription Scale, and SE scores were calculated in two different ways: factor analysis and a predefined formula. The scale's internal consistency was verified using Cronbach's acoefficient. Validity was tested by comparing the mean scores of a group of patients who did adhere to antiretroviral treatment with those of a group that did not (Mann-Whitney test) and by calculating the Spearman correlation coefficient for agreement between scores and clinical parameters. Reproducibility was verified using the Wilcoxon test, intraclass correlation coefficients (r icc) and Bland-Altman plots. RESULTS: The SE scale demonstrated good internal consistency (a= 0.87) and good reproducibility (r icc = 0.69 and r icc = 0.75). In terms of validity, the SE scale was capable of differentiating adherent patients from those who did not adhere to their antiretroviral treatment (p = 0.002) and exhibited a significant correlation with CD4 counts (r = 0.28; p = 0.04). CONCLUSIONS: The SE scale can be used to assess adherence to antiretroviral therapy in children and adolescents with HIV/AIDS, taking into account the perspective of parents/carers.

Falha terapeutica em crianças com AIDS / Therapeutic failure in children with AIDS

A falha terapeutica em criancas com aids é hoje uma das principais responsaveis pela necessidade de troca de esquemas terapeuticos. O teste de genotipagem do HIV pode ser um importante auxiliar na escolha de um novo esquema. O objetivo do trabalho foi traçar o perfil dos pacientes acompanhados no CRT-DST/AIDS/PESP apresentado falha terapeutica, além de avaliar os beneficios da genotipagem na orientação das trocas de esquemas terapêuticos de 29 pacientes avaliados. Todas as genotipagens analisadas apresentaram algum padrão de resistência aos antiretrovirais (ARV), sendo 92,8 porcento aos ITRNs, 64,2 porcento aos ITRNNs, 64,2 porcento aos IPs, 60,7 porcento aos ITRNts. Com base nos resultados das genotipagens foram feitas mudanças de esquemas ARVs, observando-se a resposta de elevação de CD4 e queda de carga viral 6 meses após as trocas, sendo que cerca de 25 porcento evoluiram com nova falha terapeutica durante a evolucao, definida com falha terapeutica posterior (nos meses subsequentes). Foi observado que os pacientes que nao apresentaram boa resposta (apos o periodo de 6 meses de observação) eram aqueles sem adesão prévia, adolescentes, classificação C3 e com uso de maior número de esquemas terapeuticos anteriores. Concluimos que a genotipagem foi um importante instrumento diagnostico para orientação de troca de ARV em pacientes com falha terapeutica, sendo a adesão, o tempo de evolução da doença, assim como a classificação e o historico prévio de uso de grande número de drogas fatores limitantes para o sucesso terapeutico.

Aids na infância / Aids in childhood

Os autores discorrem sobre a importância da infecção pela Aids na criança, abordando a epidemiologia e transmissão vertical do HIV, as manifestações clínicas e sua classificação, o diagnóstico laboratorial da criança infectada, acompanhamento do paciente pediátrico exposto ao HIV, vacinação na criança infectada, tratamento anti-retroviral e profilaxia.O trabalho conta com extensa e atualizada relação de referências bibliográficas, possibilitando ao leitor proveitoso aprofundamento no tema.

CCR5 genotypes and progression to HIV disease in perinatally infected children

The CCR5 molecule, a chemokine receptor, is the most important co-receptor for macrophage-tropic HIV-1. A 32-bp deletion in the gene encoding CCR5 (CCR5-del32) confers nearly complete resistance to HIV-1 infection in homozygotes, and slows the rate of progression to AIDS in heterozygous adults. The aim of this study was to describe the CCR5 genotypes and the characteristics of HIV disease progression in perinatally infected children. From a total of 51 children analyzed for the CCR5-del32 mutation, 18 (35 percent) were considered to be rapid progressors, 28 (55 percent) were moderate progressors and 5 (10 percent) were slow progressors. A portion of the CCR5 gene was amplified by PCR from genomic DNA followed by agarose gel electrophoresis. Forty-nine children (96 percent) carried the homozygous wild type genotype for CCR5 while 2 (4 percent) carried the heterozygous wt/del32 genotype. In the population studied, the CCR5 genotype was unable to account for the differences in pattern of the disease progression among the three groups (rapid, moderate and slow progressors), and the allele frequency of CCR5-del32 was too low to allow statistical comparisons with adequate resolving power. Studies on larger populations may help to further elucidate the role of this allele and other host factors in the regulation of HIV-1 pathogenesis in children.