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HIV-associated nephropathy (HIVAN) predominantly affects people of African ancestry living with HIV who do not receive appropriate antiretroviral therapy (ART). Childhood HIVAN is characterized by heavy proteinuria and decreased kidney function. Kidney histology shows mesangial expansion, classic or collapsing glomerulosclerosis, and microcystic renal tubular dilatation leading to kidney enlargement. The pathogenesis of HIVAN involves the kidney recruitment of inflammatory cells and the infection of kidney epithelial cells. In addition, both viral and genetic factors play key roles in this disease. Modern ART has improved the outcome and decreased the prevalence of childhood HIVAN. However, physicians have had modest success providing chronic ART to children and adolescents, and we continue to see children with HIVAN all over the world. This article discusses the progress made during the last decade in our understanding of the pathogenesis and treatment of childhood HIVAN, placing particular emphasis on the mechanisms that mediate the infection of kidney epithelial cells, and the roles of cytokines, the HIV-Tat gene, and the Apolipoprotein-1 (APOL1) gene risk variants in this disease. In view of the large number of children living with HIV at risk of developing HIVAN, better prevention and treatment programs are needed to eradicate this disease.

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S.L. was one of our first HIV-positive babies. He was born at Yale-New Haven Hospital (YNHH) in 1982. His mother was a sex worker who also injected drugs. He died at 3½ years following multiple episodes of opportunistic infection and metastatic lymphoma. In the years between 1986 and 1990, 163 HIV-positive mothers gave birth at YNHH. The mother-to-child transmission (MTCT) rate was 20 percent. Women represented 8 percent of all HIV cases in the US compared with 29 percent in New Haven. We had a six times greater proportion of children living with HIV. The mean number of HIV-exposed babies rose annually from 26 (1985-87) to 37 (1988-90). Our first team of caregivers comprised a nurse practitioner, a social worker, and me. We were, in time, joined by a growing number of colleagues. Enlightened and generous hospital administrators provided us with outpatient space and the promise of continued funding to support additional staff and in 1987, an independent Pediatric AIDS Care Program. We implemented the proven MTCT prevention guidelines articulated in the Pediatric AIDS Clinical Trials Group (PACTG) protocol 076 and by 1995, the MTCT rate at YNHH fell to 9 percent. Since 1996, the MTCT rate at YNHH has been zero percent. Combination antiretroviral therapy, cART, made its debut in the mid-1990s; five classes of drugs with multiple agents in each were licensed between 2003 and 2013. We designed individual treatment plans for each child and gradually entered an era when our clinic was populated with healthier long-term survivors. Our Program flourished, based on a multidisciplinary approach which honored interprofessional collaboration.

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OBJECTIVE: Identifying the genetic variability in vertically transmitted viruses in early infancy is important to understand the disease progression. Being important in HIV-1 disease pathogenesis, vpu gene, isolated from young infants was investigated to understand the viral characteristics. METHOD: Blood samples were obtained from 80 HIV-1 positive infants, categorized in two age groups; acute (<6 months) and early (>6-18 months). A total of 77 PCR positive samples, amplified for vpu gene, were sequenced and analyzed. RESULTS: 73 isolates belonged to subtype C. Analysis of heterogeneity of amino acid sequences in infant groups showed that in the sequences of acute age group both insertions and deletions were present while in the early age group only deletions were present. In the acute age group, a deletion of 3 residues (RAE) in the first alfa helix in one sequence and insertions of 1-2 residues (DM, GH, G and H) in the second alfa helix in 4 sequences were observed. In the early age group, deletion of 2 residues (VN) in the cytoplasmic tail region in 2 sequences was observed. Length of the amino terminal was observed to be gradually increasing with the increasing age of the infants. Protein Variation Effect Analyzer software showed that deleterious mutations were more in the acute than the early age group. Entropy analysis revealed that heterogeneity of the residues was comparatively higher in the sequences of acute than the early age group. CONCLUSION: Mutations observed in the helixes may affect the conformation and lose the ability to degrade CD4 receptors. Heterogeneity was decreasing with the increasing ages of the infants, indicating positive selection for robust virion survival.

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Objective:To investigate the change of liver function,viral load and CD4+T count in pediatric AIDS patients with HBV/HCV co-infection after HARRT therapy,and explore the effect of HBV/HCV co-infection on HAART.Methods:95 pediatric AIDS patients without HBV/HCV co-infection ( group A) ,9 pediatric AIDS patients with HBV co-infection ( group B) and 23 pediatric AIDS patients with HCV co-infection ( group C) who received HAART for 2 year were enrolled.Liver function,viral load and CD4+T count were detected before and after HAART.Results:After HAART for 2 years,26 patients (20.5%) were found with liver injury of grade 2 (1000.05 ) .Conclusion: Co-infection of HBV/HCV can aggravate the liver damage of HIV-1 infected children,but has no significant effect on HAART.

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OBJECTIVE: Kaposi's sarcoma (KS) is an angioproliferative disease frequently seen in patients with the acquired immunodeficiency syndrome (AIDS). Previous studies suggest that the HIV-1 protein Tat and Fibroblast Growth Factor 2 (FGF-2) have synergistic angiogenic effects in AIDS-KS tumors. However, the mechanisms by which FGF-2 is released and activated in KS tumors are not clearly defined. We carried out this study to determine whether an FGF-binding protein (FGFBP1 or BP1) that enhances the angiogenic activity of FGF-2 is expressed in AIDS-KS tumors, and to define whether BP1, FGF-2, and HIV-Tat protein-protein interactions could play a potential clinically role in the pathogenesis of AIDS-KS. METHODS: BP1 was localized in AIDS-KS lesions by immunohistochemistry and in situ hybridization studies. The binding of radiolabeled FGF-2 to His-tagged BP1 or the FGF-receptor 1 was assessed in the presence and absence of HIV-Tat and other viral proteins. Mice carrying tetracycline-regulated BP1 transgene mice were used to determine whether activation of BP1 during wound healing induces KS-like lesions. RESULTS: BP1 expression was detected in AIDS-KS tumor keratinocytes, spindle cells, and infiltrating mononuclear cells. In addition, HIV-Tat competed for the binding of FGF-2 to immobilized BP1, but does not affect the interactions of FGF-2 with its high affinity receptor (FGFR-1). In contrast, two other HIV-proteins, Nef and gp120, did not affect the binding of FGF-2 to BP1 or to FGFR-1. Finally, up-regulation of BP1 expression in tetracycline-regulated -conditional BP1 transgenic mice subjected to skin wounds, induced KS-like skin lesions. CONCLUSION: Taking into consideration the results of previous studies showing that both HIV-Tat and BP1 enhance the mitogenic and angiogenic activity of locally-stored FGF-2, both in vitro and in vivo, our findings suggest a novel mechanism by which the release and activity of FGFs can be modulated in AIDS-KS tumors by HIV-Tat as well as BP1.

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Purpose: The enlargement of nasopharyngeal tonsils, which leads to nasal obstruction and subsequent mouth breathing, can be caused by the presence of HIV. The aim of this research was to study nasopharyngeal tonsil sizes in HIV-infected children ranging from 6 to 13 years and to relate these findings to CD4+ T-cell counts and viral loads. Methods: Sixty children with HIV (mean age: 9 years and 8 months), infected by vertical transmission, had the sizes of their nasopharynx measured using lateral cephalometric radiographs, specifically focusing on the anatomical areas occupied by the nasopharyngeal tonsils. The children’s medical records were analyzed to assess information about TCD4+ lymphocyte count (%) and viral loads (log10). Results: The mean value for the nasopharyngeal tonsil size percentage was 70.37%±14.07%.All of the children showed moderate or accentuated hypertrophy of nasopharyngeal tonsils. The average percentage of CD4+ T-cells among the 60 HIV-infected children was 35.01%±10.76%, whereas the mean value for the viral load was 3.35±1.08 log10. Conclusion: There was no association between the size percentages of the nasopharyngeal tonsils (calculated against overall nasopharynx sizes) and CD4+ T-cell percentage (r=-0.0136; P=0.298) or the viral load log10 (r=-0.033; P=0.805).

Objetivo: A presença do HIV na tonsila faríngea pode causar seu aumento de volume, ocasionando obstrução nasal e, consequentemente, respiração bucal. O objetivo deste trabalho foi avaliar o tamanho da tonsila faríngea em crianças infectadas pelo HIV por transmissão vertical, de 6 a 13 anos de idade, relacionando-a com a contagem de células T-CD4+ e carga viral (log10).Metodologia: Sessenta crianças HIV positivo (idade média: 9 anos e 8 meses), infectadas por transmissão vertical, tiveram o tamanho da tonsila faríngea mensurado na radiografia cefalométrica lateral da face. Os prontuários das crianças foram analisados para buscar os dados de contagem de linfócitos T-CD4+ (%) e carga viral (log10). Resultados: A média do tamanho da tonsila faríngea foi de 70,37%±14,07%. As crianças apresentaram hipertrofia da tonsila faríngea considerada moderada ou acentuada. A porcentagem média de linfócitos T-CD4+ nas 60 crianças foi de 35,01%±10,76% e a média da carga viral foi de 3,35±1,08 log10. Conclusão: Não foi comprovada relação entre o tamanho da tonsila faríngea com a porcentagem de linfócitos T-CD4+ (r=-0,0136; P=0,298) e com a carga viral (r=-0,033; P=0,805).

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In this study knowledge and perceptions of parents and/or responsibles and of their HIV infected children and adolescents in a national health clinic of pediatric Aids were investigated. Observation techniques and semi-structured interviews were used before the installation of a playroom to investigate: the discovery of the HIV infection by the family, their social conditions, access to prevention and treatment and their perception of the disease. Results show that a significant number of relatives interviewed (n=28) realized that they were also HIV-carriers when their children's health deteriorated (14 or 50.0 percent); the death of the spouse occurred (6 or 21.4 percent) and by the symptoms of the disease in themselves (8 or 28.6 percent). Among the 32 children interviewed, 28 (87.5 percent) were not aware of their diagnosis and 18 (56.3 percent) were not enroled into school. Out of the 14 different schools frequented by 14 (43.8 percent) children, only 7 (50 percent) of these institutions knew about the children's diagnosis. Analysis of drawings and general playroom activities indicate that the playroom is a promising environment for the promotion of health information and continued dialog, stimulating adhesion to treatmet.

Este trabalho objetivou estudar os conhecimentos e percepções de pais/responsáveis e de suas crianças e adolescentes de um ambulatório de Aids pediátrica. Foi investigado: A descoberta do vírus pela família; as condições sociais, o acesso à prevenção e tratamento e a percepção da doença. Foram realizadas observações participantes e entrevistas semi-estruturadas, previamente à implantação de uma brinquedoteca. Os resultados revelam que 14 (50 por cento) dos familiares entrevistados (n=28) toma consciência de que são portadores do HIV através do adoecimento das crianças, 6 (21,4 por cento) pela morte de um dos cônjuges e 8 (28,6 por cento) pelos sintomas da doença deles próprios. Das crianças entrevistadas (n=32), 28 (87,5 por cento) não tinham conhecimento do diagnóstico, 18 (56,3 por cento) não freqüentavam escola. Das 14 (43,8 por cento), crianças escolarizadas em 14 diferentes instituições, 7 das escolhas (50 por cento) não tinham conhecimento do diagnóstico da criança. A análise das representações gráficas e atividades gerais na brinquetodeca indicam o seu potencial enquanto ambiente promissor para intervenção terapêutica, promoção do diálogo, podendo tornar-se estímulo à adesão ao tratamento.

Este trabajo apuntó a estudiar los conocimientos y percepciones de los padres/cuidadores y de sus niños y adolescentes en un dispensario de sida pediátrico. Se investigaron: la descubierta del virus por la familia; las condiciones sociales; el acceso a la prevención, tratamiento y la percepción de la enfermedad. Los resultados muestran que el 14-50 por ciento de los familiares (n=28) descubre que son portadores del VIH a través de la enfermedad de los niños; el 6-21,4 por ciento por la muerte de uno de los cónyuges y el 8-28,6 por ciento por la enfermedad de los mismos. De los niños (n=32), 28 (87,5 por ciento) no tenían conocimiento de la diagnosis, 18 (56,3 por ciento) no frecuentaban la escuela. De los 14 (43,8 por ciento) que lo hacían, en diferentes escuelas, 7 (50 por ciento) de las instituiciones no conocían su diagnosis. El análisis de las representaciones gráficas y actividades en la ludoteca permite caracterizarla como un ambiente prometedor a la intervención terapéutica, al diálogo y a la adherencia al tratamiento.

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In this study knowledge and perceptions of parents and/or responsibles and of their HIV infected children and adolescents in a national health clinic of pediatric Aids were investigated. Observation techniques and semi-structured interviews were used before the installation of a playroom to investigate: the discovery of the HIV infection by the family, their social conditions, access to prevention and treatment and their perception of the disease. Results show that a significant number of relatives interviewed (n=28) realized that they were also HIV-carriers when their children's health deteriorated (14 or 50.0 percent); the death of the spouse occurred (6 or 21.4 percent) and by the symptoms of the disease in themselves (8 or 28.6 percent). Among the 32 children interviewed, 28 (87.5 percent) were not aware of their diagnosis and 18 (56.3 percent) were not enroled into school. Out of the 14 different schools frequented by 14 (43.8 percent) children, only 7 (50 percent) of these institutions knew about the children's diagnosis. Analysis of drawings and general playroom activities indicate that the playroom is a promising environment for the promotion of health information and continued dialog, stimulating adhesion to treatmet.(AU)

Este trabalho objetivou estudar os conhecimentos e percepções de pais/responsáveis e de suas crianças e adolescentes de um ambulatório de Aids pediátrica. Foi investigado: A descoberta do vírus pela família; as condições sociais, o acesso à prevenção e tratamento e a percepção da doença. Foram realizadas observações participantes e entrevistas semi-estruturadas, previamente à implantação de uma brinquedoteca. Os resultados revelam que 14 (50 por cento) dos familiares entrevistados (n=28) toma consciência de que são portadores do HIV através do adoecimento das crianças, 6 (21,4 por cento) pela morte de um dos cônjuges e 8 (28,6 por cento) pelos sintomas da doença deles próprios. Das crianças entrevistadas (n=32), 28 (87,5 por cento) não tinham conhecimento do diagnóstico, 18 (56,3 por cento) não freqüentavam escola. Das 14 (43,8 por cento), crianças escolarizadas em 14 diferentes instituições, 7 das escolhas (50 por cento) não tinham conhecimento do diagnóstico da criança. A análise das representações gráficas e atividades gerais na brinquetodeca indicam o seu potencial enquanto ambiente promissor para intervenção terapêutica, promoção do diálogo, podendo tornar-se estímulo à adesão ao tratamento.(AU)

Este trabajo apuntó a estudiar los conocimientos y percepciones de los padres/cuidadores y de sus niños y adolescentes en un dispensario de sida pediátrico. Se investigaron: la descubierta del virus por la familia; las condiciones sociales; el acceso a la prevención, tratamiento y la percepción de la enfermedad. Los resultados muestran que el 14-50 por ciento de los familiares (n=28) descubre que son portadores del VIH a través de la enfermedad de los niños; el 6-21,4 por ciento por la muerte de uno de los cónyuges y el 8-28,6 por ciento por la enfermedad de los mismos. De los niños (n=32), 28 (87,5 por ciento) no tenían conocimiento de la diagnosis, 18 (56,3 por ciento) no frecuentaban la escuela. De los 14 (43,8 por ciento) que lo hacían, en diferentes escuelas, 7 (50 por ciento) de las instituiciones no conocían su diagnosis. El análisis de las representaciones gráficas y actividades en la ludoteca permite caracterizarla como un ambiente prometedor a la intervención terapéutica, al diálogo y a la adherencia al tratamiento.(AU)

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