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.

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.

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.

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. .

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.