Hepatoesplenomegalia relacionada a linfoma de Burkitt en paciente pediátrico / Hepatoesplenomegalia related to Burkitt´s lymphoma in a pediatric patient

RESUMEN El linfoma de Burkitt, se trata de un subtipo poco frecuente del linfoma no Hodgkin, con elevada frecuencia en aquellos pacientes con sida. La hepatoesplenomegalia es un signo clínico de gran importancia para el diagnóstico oportuno de algunas patologías; entre los mecanismos de formación de la hepatoesplenomegalia se encuentra la infiltración celular, ocasionada por la migración de células tumorales. Se presenta por inflamaciones debido a la presencia de infecciones por virus o bacterias las cuales son muy comunes en pacientes con sida. Se presentó un caso de un paciente masculino de 4 años, diagnosticado con VIH positivo, con la configuración correspondiente de criterios clínicos en clasificación C para sida. El cual desarrolló a nivel de cavidad oral un Burkitt primario, que se acompañó de hepatoesplenomegalia. Se pretendió describir la relación y el comportamiento de este tipo de linfoma con la hepatoesplenomegalia, así como la repercusión a nivel del sistema estomatognático, a nivel sistémico y el plan de tratamiento. Por el cuadro clínico e inmunológico del paciente estudiado, se planteó un pronóstico reservado por presentar un cuadro clínico infrecuente, en el que se observó Burkitt; tanto a nivel del sistema estomatognático como a nivel abdominal. Se hizo necesario realizar un diagnóstico oportuno y certero para iniciar el tratamiento a tiempo, se comenzó inmediatamente con tratamiento (AU).

ABSTRACT Burkitt lymphoma (BL) is a rare subtype of non-Hodgkin lymphoma, with high frequency in those patients with AIDS. Hepatosplenomegaly is a clinical sign of great importance for the timely diagnosis of some pathologies; cellular infiltration is found among the mechanisms of hepatosplenomegaly formation; it is caused by the migration of tumor cells. It emerges by inflammations due to the presence of infections by virus or bacteria which are very common in patients with AIDS. The authors present the case of a male patient, aged 4 years, with a positive HIV diagnosis, and the correspondent configuration of clinical criteria in C classification for AIDS, who developed a primary Burkitt lymphoma at the level of oral cavity We present the case of a 4-year-old male patient diagnosed with HIV positive, with the corresponding configuration of clinical criteria in classification C for AIDS; who developed a primary LB at the oral cavity level that was accompanied by hepatosplenomegaly. The authors pretended to describe the relation and behavior of this kind of lymphoma with hepatosplenomegaly, and also the repercussion at the stomatognathic level, at the systemic level and the treatment plan. Due to the clinical and immunological characteristics of the studied patient a reserved prognosis was given because of presenting infrequent clinical characteristics in which a Burkitt was observed both, at the stomatognathic and at the abdominal level. It was necessary to make an opportune and accurate diagnosis to begin the treatment on time (AU).

Reflexões humanísticas em serviço de atendimento especializado em HIV / Humanistic reflections on specialized HIV care service / Reflexiones humanísticas en un servicio de atención especializado en VIH

Resumo A postura do médico em relação a diagnóstico e esclarecimentos ao paciente infectado pelo vírus da imunodeficiência humana baseia-se principalmente na percepção pessoal e experiência humanística. O objetivo deste estudo foi relatar a experiência de estudantes de medicina do sexto período do Centro Universitário Metropolitano da Amazônia, em Belém/PA, durante as aulas do módulo de Habilidades Clínicas (Eixo Infectologia) no Centro de Atenção à Saúde em Doenças Infecciosas Adquiridas. Depois de prestarem atendimentos ambulatoriais e discutirem casos clínicos por cinco meses, os estudantes se deram conta da necessidade de humanização nessa área, considerando questões biopsicossociais. De modo geral, a experiência ampliou os conhecimentos adquiridos nas aulas e permitiu aplicar o cuidado integral ao paciente, além de estimular formação mais humanística e crítica desses profissionais de saúde.

Abstract The physicians's attitude towards diagnosis and clarifications to the patient infected by the human immunodeficiency virus is based mainly on personal perception and humanistic experience. The objective of this study was to report the experience of medical students from the sixth period of the Centro Universitário Metropolitano da Amazônia, in Belém, Pará, Brazil, during classes of the Clinical Skills module (Infectious Axis) at the Center for Attention on Acquired Infectious Diseases. After providing outpatient care and discussing clinical cases for five months and considering biopsychosocial issues, the students realized a need for humanization in this area. The experience expanded the knowledge acquired in class and allowed the delivery of comprehensive care to the patient, in addition to encouraging more humanistic and critical training of these health professionals.

Resumen La actitud del médico respecto al diagnóstico y la aclaración de la condición del paciente infectado por el VIH está relacionada con la percepción personal y la experiencia humanística. El presente estudio tuvo el objetivo de presentar la experiencia de estudiantes de medicina del sexto período del Centro Universitário Metropolitano da Amazônia, en Belém, Pará, Brasil, durante las clases del módulo Habilidades Clínicas (Eje Infectología) en el Centro de Atención de Enfermedades Infecciosas Adquiridas. Los estudiantes ofrecieron atención ambulatoria y tuvieron discusión de casos durante cinco meses y pudieron advertir la necesidad de humanización en esta área debido a problemas biopsicosociales. La experiencia brindó la oportunidad de ampliar los conocimientos adquiridos durante las clases y aplicar una atención integral al paciente, y estimular la capacitación de profesionales de la salud con un perfil humanístico y crítico.

Antigenic competition in CD4+ T cell responses in a randomized, multicenter, double-blind clinical HIV vaccine trial.

T cell responses have been implicated in reduced risk of HIV acquisition in uninfected persons and control of viral replication in HIV-infected individuals. HIV Gag-specific T cells have been predominantly associated with post-infection control, whereas Env antigens are the target for protective antibodies; therefore, inclusion of both antigens is common in HIV vaccine design. However, inclusion of multiple antigens may provoke antigenic competition, reducing the potential effectiveness of the vaccine. HVTN 084 was a randomized, multicenter, double-blind phase 1 trial to investigate whether adding Env to a Gag/Pol vaccine decreases the magnitude or breadth of Gag/Pol-specific T cell responses. Fifty volunteers each received one intramuscular injection of 1 × 1010 particle units (PU) of rAd5 Gag/Pol and EnvA/B/C (3:1:1:1 mixture) or 5 × 109 PU of rAd5 Gag/Pol. CD4+ T cell responses to Gag/Pol measured 4 weeks after vaccination by cytokine expression were significantly higher in the group vaccinated without Env, whereas CD8+ T cell responses did not differ significantly between the two groups. Mapping of individual epitopes revealed greater breadth of the Gag/Pol-specific T cell response in the absence of Env compared to Env coimmunization. Addition of an Env component to a Gag/Pol vaccine led to reduced Gag/Pol CD4+ T cell response rate and magnitude as well as reduced epitope breadth, confirming the presence of antigenic competition. Therefore, T cell-based vaccine strategies should aim at choosing a minimalist set of antigens to reduce interference of individual vaccine components with the induction of the maximally achievable immune response.

Polyfunctional CD8+ T-Cell Response to Autologous Peptides from Protease and Reverse Transcriptase of HIV-1 Clade B.

BACKGROUND: The diversity of the HIV proteome influences the cellular response and development of an effective vaccine, particularly due to the generation of viral variants with mutations located within CD8+ T-cell epitopes. These mutations can affect the recognition of the epitopes, that may result in the selection of HIV variants with mutated epitopes (autologous epitopes) and different CD8+ T-cell functional profiles. OBJECTIVE: To determine the phenotype and functionality of CD8+ T-cell from HIV-infected Colombian patients in response to autologous and consensus peptides derived from HIV-1 clade B protease and reverse transcriptase (RT). METHODS: By flow cytometry, we compared the ex vivo CD8+ T-cell responses from HIV-infected patients to autologous and consensus peptides derived from HIV-1 clade B protease and RT, restricted by HLA-B*35, HLA-B*44 and HLA-B*51 alleles. RESULTS: Although autologous peptides restricted by HLA-B*35 and HLA-B*44 did not show any differences compared with consensus peptides, we observed the induction of a higher polyfunctional profile of CD8+ T-cells by autologous peptides restricted by HLA-B*51, particularly by the production of interferon-γ and macrophage inflammatory protein-1ß. The response by different memory CD8+ T-cell populations was comparable between autologous vs. consensus peptides. In addition, the magnitude of the polyfunctional response induced by the HLA-B*51-restricted QRPLVTIRI autologous epitope correlated with low viremia. CONCLUSION: Autologous peptides should be considered for the evaluation of HIV-specific CD8+ Tcell responses and to reveal some relevant epitopes that could be useful for therapeutic strategies aiming to promote polyfunctional CD8+ T-cell responses in a specific population of HIV-infected patients.

Aleitamento materno: a visão de puérperas soropositivas para hiv e htlv quanto a não amamentação / Breastfeeding: the vision of soropositive puerperos for hiv and htlv regarding non-breastfeeding

Introdução: O aleitamento materno é o mais simples método de vínculo, proteção e nutrição para a criança. Entretanto, o aleitamento pode ser contraindicado nos casos em que a puérpera possuir soropositividade para o HIV e HTLV. Objetivo: Conhecer a visão da puérpera soropositiva para HIV e HTLV quanto a não amamentação. Método: Descritivo com abordagem qualitativa, pois propicia conhecer a natureza e processo que constitui o objeto de estudo, descrevendo-os e interpretando-os. Enquanto que a abordagem qualitativa possibilitará compreender a realidade estudada. Realizado em um hospital materno-infantil referência em gestação de alto risco. Participaram oito puérperas soropositivas para HIV/HTLV no período de março-abril de 2017. Resultado: Três categorias: entendimento relacionado ao não aleitamento materno; sentimento da puérpera quanto a não amamentação e conhecimento sobre o funcionamento e importância do banco de leite humano. Considerações finais: Pode-se compreender a visão da puérpera sobre o aleitamento materno, falta de conhecimento das participantes advindas do interior e falta de informações quanto ao HTLV, salientando a importância da interação entre a enfermagem e a puérpera a fim de melhor orientá-la.(AU)

Using Dendritic Cell-Based Immunotherapy to Treat HIV: How Can This Strategy be Improved?

Harnessing dendritic cells (DC) to treat HIV infection is considered a key strategy to improve anti-HIV treatment and promote the discovery of functional or sterilizing cures. Although this strategy represents a promising approach, the results of currently published trials suggest that opportunities to optimize its performance still exist. In addition to the genetic and clinical characteristics of patients, the efficacy of DC-based immunotherapy depends on the quality of the vaccine product, which is composed of precursor-derived DC and an antigen for pulsing. Here, we focus on some factors that can interfere with vaccine production and should thus be considered to improve DC-based immunotherapy for HIV infection.

Evaluación de la estabilidad del sistema de diagnóstico inmunoenzimático DAVIH VIH-2 / Evaluation of the stability of the immunoenzymatic diagnostic system DAVIH VIH-2

Introducción: el estudio de la estabilidad de los componentes y el producto terminado constituye un importante requisito regulatorio en los diagnosticadores. Objetivo: realizar un estudio de estabilidad en tiempo real durante doce meses del sistema inmunoenzimático (ELISA) DAVIH VIH-2. Métodos: se realizó un estudio de estabilidad en tiempo real durante doce meses en tres lotes del diagnosticador DAVIH VIH-2, ELISA indirecto diseñado para la detección de anticuerpos contra el virus de inmunodeficiencia humana tipo 2 en suero o plasma humano. Se controlaron los requisitos de calidad de los componentes de acuerdo a sus especificaciones. Se estudió la normalidad de valores de densidad óptica/valor límite y la homogeneidad de las medias y varianzas mediante las dócimas de Grubbs y Cochran. Se estimó la precisión en los controles positivo y negativo del sistema y en seis muestras con diferente reactividad al virus de inmunodeficiencia humana tipo 2 mediante el cálculo del coeficiente de variación y se confeccionaron las cartas de control de los valores de las medias de densidad óptica respecto al tiempo. Resultados: los requisitos de calidad de cada componente se cumplieron durante 12 meses, excepto las características funcionales del conjugado a partir de los seis meses. Los valores en las dócimas de Grubbs y Cochran fueron menores que los valores críticos tabulados para α del 1 y 5 por ciento por lo que existió homogeneidad en las medias y las varianzas en todo el periodo. El coeficiente de variación se mantuvo inferior al 10 por ciento excepto en las muestras con reactividad media y baja, mientras que en las cartas de control, los valores de densidad óptica se mantuvieron en el límite de la media ±2 desviaciones estándar hasta el noveno mes. Conclusiones: con estos resultados se propuso un periodo de validez para el producto terminado de 4 meses con un 50 por ciento de cobertura(AU)

Introduction: the study of the components stability and the finished product is an important regulatory requirement for diagnostic tests. Objective: to carry out, for twelve months, a stability in real time study on the immunosorbent assay system (ELISA) DAVIH HIV-2. Methods: a real-time stability study was carried out for twelve months to three lots of the ELISA indirect diagnostic test DAHIV HVI/2, designed to detect antibodies to the human immunodeficiency virus type 2 in human serum or plasma. The components quality requirements by their specifications were monitored. The normality of optical density values/limit value and homogeneity of the means and variances were studied by using Grubbs and Cochra tests. Precision was estimated at the systems positive and negative controls and in six samples with different reactivity to the human immunodeficiency virus type 2, by calculating the variation coefficient and control records were elaborated of the mean values of optical density compared to time. Results: the quality requirements of each component were met for 12 months, except the kits functional characteristics from the sixth months on. The values in Grubbs and Cochran tests were lower than the a-tabulated critical values for 1 and 5 percent, so homogeneity manifested in the means and variances throughout the period. The variation coefficient remained under 10 percent, except in the samples with low and middle reactivity, while in control records, the optical density values remained within the mean limits: ±2 standard deviation, up to the ninth month. Conclusions: after these results, four month was proposed as a validity period for the finished product, with coverage of 50 percent(AU)

Multiple Approaches for Increasing the Immunogenicity of an Epitope-Based Anti-HIV Vaccine.

The development of a highly effective vaccine against the human immunodeficiency virus (HIV) will likely be based on rational vaccine design, since traditional vaccine approaches have failed so far. In recent years, an understanding of what type of immune response is protective against infection and/or disease facilitated vaccine design. T cell-based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. In this context, CD4(+) T cells play a direct cytotoxic role and are also important for the generation and maintenance of functional CD8(+) T and B cell responses. The use of MHC-binding algorithms has allowed the identification of novel CD4(+) T cell epitopes that could be used in vaccine design, the so-called epitope-driven vaccine design. Epitope-based vaccines have the ability to focus the immune response on highly antigenic, conserved epitopes that are fully recognized by the target population. We have recently mapped a set of conserved multiple HLA-DR-binding HIV-1 CD4 epitopes and observed interferon (IFN)-γ-producing CD4(+) T cells when we tested these peptides in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals. We then designed multiepitopic DNA vaccines that induced broad and polyfunctional T cell responses in immunized mice. In this review we will focus on alternative strategies to increase the immunogenicity of an epitope-based vaccine against HIV infection.

[Use of a synthetic peptide of HIV-2 glycoprotein 36 in antigen mixtures for the immunodiagnosis of HIV types 1 and 2]. / Uso de un péptido sintético de la glucoproteína 36 del VIH 2 en mezclas de antígenos para el inmunodiagnóstico de la infección por VIH tipo 1 y 2.

INTRODUCTION: The HIV-2 glycoprotein 36 (gp36) is often used in ELISA. An evaluation of the diagnostic indexes of antigen mixtures with a synthetic peptide of HIV2 gp36 (5) is performed in this study. METHODS: Five mixtures of gp36 (5) and the recombinant proteins of HIV1/2 were prepared. A total of 1306 samples were evaluated with UMELISA HIV1+2 RECOMBINANT used as reference. RESULTS: The variant (V-1) showed very good agreement as regards the reference method. CONCLUSION: The V-1 variant was shown to be highly effective in the immunodiagnosis of HIV 1/2.

Innate activation of MDC and NK cells in high-risk HIV-1-exposed seronegative IV-drug users who share needles when compared with low-risk nonsharing IV-drug user controls.

BACKGROUND: Previous studies have described increased innate immune activation in HIV-1-exposed seronegative intravenous drug users (HESN-IDU), but have not addressed the independent role of injected drugs and/or repeated injections in driving immune activation. METHODS: In this study, we investigated innate [natural killer (NK) cells and dendritic cells] and adaptive (HIV-specific antibody and CD8 T cell) immune parameters among a high-risk cohort of needle-sharing HESN-IDU subjects and compared them with low-risk nonsharing IDU subjects (NS-IDU) and non-drug-user controls. RESULTS: We observed that HIV-specific antibody and CD8 T-cell responses were not detected in HESN-IDU subjects, yet innate immune cell activation was found to be significantly increased on NK cells (CD69 and CD107a upregulation) and myeloid dendritic cells (CD40 and CD83 upregulation) when compared with NS-IDU subjects or non-drug-user controls (P < 0.01 and P < 0.05, respectively). HESN-IDU subjects maintained strong NK-cell CD107a degranulation and cytokine (IFN-gamma, TNF-alpha, and MIP-1 beta) production after target cell incubation suggesting that constitutive innate activation does not induce functional exhaustion of innate cells in HESN-IDU subjects. NK activation in HESN-IDU subjects was independent of drug use patterns but was durable over time and correlated with plasma levels of IP-10 by Luminex analysis (ρ = 0.5073, P = 0.0059, n = 28). CONCLUSIONS: Our results indicate that heightened innate immune cell activation in HESN-IDU subjects is not the result of the IV drugs and repeated injection practice itself, but to repeated exposure to factors intrinsic to sharing needles (ie, exposure to pathogens or heterologous cells among donor blood).

Resposta imune celular contra peptídeos crípticos do HIV-1 / Cellular immune response against HIV-1 cryptic peptides

INTRODUÇÃO E OBJETIVOS: Uma fonte secundária e não convencional de peptídeos que se ligam as moléculas MHC de classe I tem sido descrita como responsável por produzir peptídeos crípticos. Esses peptídeos são imunogênicos e portanto, capazes de induzir uma resposta imunológica por células T e assim, contribuir com a resposta total exercida pelas células T CD8+, colaborando na pressão que leva HIV-1 ao processo de mutação, e consequentemente ao escape viral. Alguns pacientes, que correspondem a menos de 5% da população infectada, são capazes de naturalmente controlar a progressão da doença, mantendo a contagem de célula T CD4+ acima de 500 células/uL ou mantendo a carga viral abaixo de 2.000 cópias/mL, por ao menos 12 meses, sem ser submetido a tratamento com antirretrovirais ou esquema HAART. Avaliar a resposta imunológica destes pacientes, controladores da infecção, contra peptídeos crípticos pode nos fornecer informações importantes que colaborem com o desenvolvimento de novas estratégias preventivas. METODOLOGIA: A resposta imunológica contra peptídeos crípticos, estes derivados da transcrição da seqüência consenso e da seqüência inversa do gene do HIV-1, foram avaliados em vários conjuntos (pools), utilizando amostras coletadas de pacientes controladores, tanto avirêmicos, também conhecidos como controladores de elite (carga viral < limite de detecção), bem como virêmicos (carga viral < 2.000 cópias/mL) e, de pacientes progressores. Foi observada que a resposta imunológica contra peptídeos crípticos é mais freqüente, com maior amplitude e magnitude entre os pacientes controladores comparados ao que foi observado entre pacientes progressores. Esta resposta, entretanto, parece inverter ao longo da infecção, como observada utilizando as amostras coletadas em momento tardio da infecção, onde os controladores parecem perder sua capacidade de responder aos peptídeos crípticos, enquanto que os progressores desenvolveram resposta, ressaltando...

BACKGROUND: A second and unconventional source of peptides that bind to MHC class I molecule has been described to produce cryptic peptides, which are immunogenic and are able elicit T cell response, that contributes to total CD8+ T cell immune response and then exert mutation pressure on HIV-1, leading to virus escape. Some rare patients, less than 5% of infected population, are naturally able to control disease progression, either maintaining CD4+ T cells over 500 cells/uL or viral load under 2,000 copies/mL, without being treated with HAART, for at least 12 months. Understanding their immune response to cryptic peptides might be a great value to help on developing better prevention strategies. METHODOLOGY: Immune response to cryptic peptides, derived from sense and antisense transcription of HIV-1, was evaluated in pools using samples from Elite (aviremic) or HIV (viremic, < 2,000 copies/mL) controllers and progressors. Immune response to cryptic peptides are more frequent, with a larger breadth and of greater magnitude in controllers than in progressors, and this response is inversed seen in a later time point, when controllers seems to lose this response, while progressors developed it, showing cryptic peptides immune response to different pools, suggesting that immune response to cryptic peptides might play some role in pressuring the virus mutation escape. CONCLUSIONS AND SIGNIFICANCE: cryptic peptides can elicit immune response and help to explain how some virus selection happens, either by changing expression of crucial HIV-1 proteins or generating defective virus. They can be included in vaccine design for enhancing the magnitude and breadth of T cell immune response and consequently the protection against infection or progression of HIV-1 infection.

The first, the next, and the cinematographed versions of AZT / Las versiones primera, próxima y cinematográficas de AZT

Ronald Woodroof died of AIDS in September 12, 1992, seven years after he was diagnosed. A lower dose of AZT became widely used in later drug combinations that saved millions of lives". These words end the film Dallas Buyers Club, a recent, highly awarded movie, that tells the true story of a cowboy diagnosed with AIDS in 1985 and illegally receives the firsthand antiviral AZT but, due to the severe side effects that the drug afflicted, begins to experiment with ­ and illicitly distribute among the "Club" ­ non-FDA approved remedies in search of a better treatment for himself and other AIDS patients. Perhaps owing to an artistic strategy, the movie waits until the last couple of lines to do justice to AZT and the impact it had in dealing with AIDS at that day and age

Microbiota bucal de pacientes HIV positivos: relação com o uso de drogas antirretrovirais e condições de saúde / Oral microbiota in HIV positive patients: relationship with the use of antiretroviral drugs and health conditions

Os medicamentos antirretrovirais têm a finalidade de impedir a replicação viral, mantendo indiretamente a contagem de linfócitos T CD4+ estável, com isso, as infecções oportunistas diminuem, havendo melhora da qualidade de vida do indivíduo infectado pelo HIV, porém, inibidores de proteases e da transcriptase reversa também estão associados a efeitos adversos e risco de desenvolvimento de resistência medicamentosa. Além disso, ainda não está claro o efeito dessas terapias na microbiota bucal. Objetivo: O objetivo desse estudo foi investigar, em biofilme supra e subgengival de pacientes HIV positivos com diferentes condições periodontais e imunológicas, o efeito da terapia antirretroviral sobre microrganismos que podem estar associados a infecções oportunistas locais ou sistêmicas. Materiais e métodos: Foram obtidos dados sobre as condições de saúde, uso antirretrovirais e amostras de biofilme supra e subgengival de 118 pacientes HIV positivos de ambos os sexos divididos em dois grupos (usuários e não usuários de HAART). Essas amostras foram submetidas à detecção de microrganismos por PCR. Cálculos de Odds ratios foram realizados para determinar a relevância de inter-relações entre diferentes microrganismos e a significância dos parâmetros clínicos e microbiológicos foi determinada através de regressão logística multivariada. Resultados: Foram encontrados principalmente Tannerella forsythia, Campylobacter rectus, Acninomyces israelli, Staphylococcus sp, Citomegalovírus e Enterobacteriaceae nos pacientes. Treponema denticola, Fusobacterium nucleatum, Mollicutes, Actinomyces israelli e Staphylococcus sp em biofilme subgengival tiveram correlação significativa com os grupos de antirretrovirais (p < 0,05). Na comparação entre os grupos, somente Enterococcus faecalis e Pseudomonas aeruginosa tiveram significância com maior prevalência para o grupo de não usuários de antirretrovirais. Conclusão: Não houve diferenças significantes entre os grupos...

Introduction: Antiretrovirals are used in order to prevent viral replication while maintaining CD4 + T lymphocytes stable and low viral load, thus the occurrence of opportunistic infections decreases with an improvement in the quality of life of HIV-infected individual. As is known, protease inhibitors and reverse transcriptase are also associated with risk of adverse effects and development of drug resistance, however, it remains unclear the effect of these therapies on oral microbiota. Objective: The aim of this study was to investigate, in biofilm supra and subgingival in HIV - positive patients with different periodontal and immunological conditions, the effect of HAART on microorganisms that may be associated with local or systemic opportunistic infections. Materials and methods: Data on health conditions, use or nonuse of antiretroviral and biofilm samples supra and subgingival of 118 HIV - positive patients of both sexes, divided into two groups (users and nonusers of HAART), were obtained. These samples were subjected to PCR for detection of microorganisms. Odds ratio calculations were performed to determine the relevance of inter - relations between different microorganisms and the significance of clinical and microbiological parameters were determined using multivariate logistic regression. Results: Mainly T. forsythia, C. rectus, A. israelli, Staphylococcus sp and CMV were found. T denticola, F nucleatum, mollicutis, A. israelli and Staphylococcus sp in subgingival biofilm showed significant correlation (p <0.05) with antiretrovirals groups. Only E. faecalis and P. aeruginosa were significant with higher incidence in no HAART users group. Conclusion: There were no significant differences in supra and subgingival biofilm for most microbiota of HAART users and non-users...

Microbiota bucal de pacientes HIV positivos: relação com o uso de drogas antirretrovirais e condições de saúde / Oral microbiota in HIV positive patients: relationship with the use of antiretroviral drugs and health conditions

Introdução: Os medicamentos antirretrovirais têm a finalidade de impedir a replicação viral, mantendo indiretamente a contagem de linfócitos T CD4+ estável, com isso, as infecções oportunistas diminuem, havendo melhora da qualidade de vida do indivíduo infectado pelo HIV, porém, inibidores de proteases e da transcriptase reversa também estão associados a efeitos adversos e risco de desenvolvimento de resistência medicamentosa. Além disso, ainda não está claro o efeito dessas terapias na microbiota bucal. Objetivo: O objetivo desse estudo foi investigar, em biofilme supra e subgengival de pacientes HIV positivos com diferentes condições periodontais e imunológicas, o efeito da terapia antirretroviral sobre microrganismos que podem estar associados a infecções oportunistas locais ou sistêmicas. Materiais e métodos: Foram obtidos dados sobre as condições de saúde, uso antirretrovirais e amostras de biofilme supra e subgengival de 118 pacientes HIV positivos de ambos os sexos divididos em dois grupos (usuários e não usuários de HAART). Essas amostras foram submetidas à detecção de microrganismos por PCR. Cálculos de Odds ratios foram realizados para determinar a relevância de inter-relações entre diferentes microrganismos e a significância dos parâmetros clínicos e microbiológicos foi determinada através de regressão logística multivariada. Resultados: Foram encontrados principalmente Tannerella forsythia, Campylobacter rectus, Acninomyces israelli, Staphylococcus sp, Citomegalovírus e Enterobacteriaceae nos pacientes. Treponema denticola, Fusobacterium nucleatum, Mollicutes, Actinomyces israelli e Staphylococcus sp em biofilme subgengival tiveram correlação significativa com os grupos de antirretrovirais (p < 0,05). Na comparação entre os grupos, somente Enterococcus faecalis e Pseudomonas aeruginosa tiveram significância com maior prevalência para o grupo de não usuários de antirretrovirais. Conclusão: Não houve diferenças significantes entre os grupos para a...

Introduction: Antiretrovirals are used in order to prevent viral replication while maintaining CD4 + T lymphocytes stable and low viral load, thus the occurrence of opportunistic infections decreases with an improvement in the quality of life of HIV-infected individual. As is known, protease inhibitors and reverse transcriptase are also associated with risk of adverse effects and development of drug resistance, however, it remains unclear the effect of these therapies on oral microbiota. Objective: The aim of this study was to investigate, in biofilm supra and subgingival in HIV - positive patients with different periodontal and immunological conditions, the effect of HAART on microorganisms that may be associated with local or systemic opportunistic infections. Materials and methods: Data on health conditions, use or nonuse of antiretroviral and biofilm samples supra and subgingival of 118 HIV - positive patients of both sexes, divided into two groups (users and nonusers of HAART), were obtained. These samples were subjected to PCR for detection of microorganisms. Odds ratio calculations were performed to determine the relevance of inter - relations between different microorganisms and the significance of clinical and microbiological parameters were determined using multivariate logistic regression. Results: Mainly T. forsythia, C. rectus, A. israelli, Staphylococcus sp and CMV were found. T denticola, F nucleatum, mollicutis, A. israelli and Staphylococcus sp in subgingival biofilm showed significant correlation (p <0.05) with antiretrovirals groups. Only E. faecalis and P. aeruginosa were significant with higher incidence in no HAART users group. Conclusion: There were no significant differences in supra and subgingival biofilm for most microbiota of HAART users and non-users

The impact of pregnancy on the HIV-1-specific T cell function in infected pregnant women.

Evidences indicate that pregnancy can alter the Ag-specific T-cell responses. This work aims to evaluate the impact of pregnancy on the in vitro HIV-1-specific immune response. As compared with non-pregnant patients, lower T-cell proliferation and higher IL-10 production were observed in T-cell cultures from pregnant patients following addition of either mitogens or HIV-1 antigens. In our system, the main T lymphocyte subset involved in producing IL-10 was CD4(+)FoxP3(-). Depletion of CD4(+) cells elevated TNF-α and IFN-γ production. Interestingly, the in vitro HIV-1 replication was lower in cell cultures from pregnant patients, and it was inversely related to IL-10 production. In these cultures, the neutralization of IL-10 by anti-IL-10 mAb elevated TNF-α release and HIV-1 replication. In conclusion, our results reveal that pregnancy-related events should favor the expansion of HIV-1-specific IL-10-secreting CD4(+) T-cells in HIV-1-infected women, which should, in the scenario of pregnancy, help to reduce the risk of vertical HIV-1 transmission.

Perspectivas de curación: DermaVir, una vacuna de ADN con efecto terapéutico contra el VIH/sida y desarrollada racionalmente / Towards a cure: DermaVir, a rationally designed therapeutic DNA vaccine against HIV/AIDS

Hallazgos recientes en el área de la intensificación de los tratamientos antirretrovirales demuestran que la forma de llegar a una curación para el VIH exige la inclusión de nuevas estrategias de tratamiento como las vacunas terapéuticas. La vacuna terapéutica DermaVir incluye elementos tecnológicos clave en el diseño de una vacuna racional: un único inmunógeno plásmido de ADN (pADN) que expresa a 15 antígenos del VIH, formulación de nanomedicina y una única administración tópica de la vacuna enfocada a las células dendríticas. Luego de su administración tópica sobre la piel preparada, las células epidérmicas de Langerhans activadas transportan la nanomedicina DermaVir a los nódulos linfáticos para expresar a los antígenos del VIH codificados como pADN e inducir a las células T precursoras/de memoria con una alta capacidad de proliferación. Se han demostrdo la seguridad, la inmunogenicidad y la eficacia preliminar de la DermaVir en varios modelos animales y en humanos con infección por VIH. Esta novedosa tecnología de vacunación terapéutica podría constituir un nuevo paradigma en el trtamiento contra el VIH.

Recent findings on the field of antiretroviral treatment intesnsification demonstrate thar the way towards a cure for HIV requires the involvement of novel treatment strategies like therapeutic vaccines. DermaVir therapeutic vaccine includes key technological elements of rational vaccine design: a single plasmid DNA (pDNA) immunogen that expresses 15 HIV antigens, nanomedicine formulation and a unique dendritic cell-targeting topical vaccine administration. Following topical administration on the prepared skin, DermaVir nanomedicine is transported by activated epidermal Langerhans cells to the lymph nodes to express the pDNA-encoded HIV antigens and induce precursor/memory T cells with high proliferation capacity. Safety, immunogenicity and preliminary efficacy of DermaVir have been demonstrated in several animal models and HIV-infected human subjects. This novel therapeutic vaccination technology might offer a new treatment paradigm against HIV.

Perspectivas de curación: DermaVir, una vacuna de ADN con efecto terapéutico contra el VIH/sida y desarrollada racionalmente / Towards a cure: DermaVir, a rationally designed therapeutic DNA vaccine against HIV/AIDS

Hallazgos recientes en el área de la intensificación de los tratamientos antirretrovirales demuestran que la forma de llegar a una curación para el VIH exige la inclusión de nuevas estrategias de tratamiento como las vacunas terapéuticas. La vacuna terapéutica DermaVir incluye elementos tecnológicos clave en el diseño de una vacuna racional: un único inmunógeno plásmido de ADN (pADN) que expresa a 15 antígenos del VIH, formulación de nanomedicina y una única administración tópica de la vacuna enfocada a las células dendríticas. Luego de su administración tópica sobre la piel preparada, las células epidérmicas de Langerhans activadas transportan la nanomedicina DermaVir a los nódulos linfáticos para expresar a los antígenos del VIH codificados como pADN e inducir a las células T precursoras/de memoria con una alta capacidad de proliferación. Se han demostrdo la seguridad, la inmunogenicidad y la eficacia preliminar de la DermaVir en varios modelos animales y en humanos con infección por VIH. Esta novedosa tecnología de vacunación terapéutica podría constituir un nuevo paradigma en el trtamiento contra el VIH.(AU)

Recent findings on the field of antiretroviral treatment intesnsification demonstrate thar the way towards a cure for HIV requires the involvement of novel treatment strategies like therapeutic vaccines. DermaVir therapeutic vaccine includes key technological elements of rational vaccine design: a single plasmid DNA (pDNA) immunogen that expresses 15 HIV antigens, nanomedicine formulation and a unique dendritic cell-targeting topical vaccine administration. Following topical administration on the prepared skin, DermaVir nanomedicine is transported by activated epidermal Langerhans cells to the lymph nodes to express the pDNA-encoded HIV antigens and induce precursor/memory T cells with high proliferation capacity. Safety, immunogenicity and preliminary efficacy of DermaVir have been demonstrated in several animal models and HIV-infected human subjects. This novel therapeutic vaccination technology might offer a new treatment paradigm against HIV.(AU)

Perspectivas de curación: DermaVir, una vacuna de ADN con efecto terapéutico contra el VIH/sida y desarrollada racionalmente / Towards a cure: DermaVir, a rationally designed therapeutic DNA vaccine against HIV/AIDS

Hallazgos recientes en el área de la intensificación de los tratamientos antirretrovirales demuestran que la forma de llegar a una curación para el VIH exige la inclusión de nuevas estrategias de tratamiento como las vacunas terapéuticas. La vacuna terapéutica DermaVir incluye elementos tecnológicos clave en el diseño de una vacuna racional: un único inmunógeno plásmido de ADN (pADN) que expresa a 15 antígenos del VIH, formulación de nanomedicina y una única administración tópica de la vacuna enfocada a las células dendríticas. Luego de su administración tópica sobre la piel preparada, las células epidérmicas de Langerhans activadas transportan la nanomedicina DermaVir a los nódulos linfáticos para expresar a los antígenos del VIH codificados como pADN e inducir a las células T precursoras/de memoria con una alta capacidad de proliferación. Se han demostrdo la seguridad, la inmunogenicidad y la eficacia preliminar de la DermaVir en varios modelos animales y en humanos con infección por VIH. Esta novedosa tecnología de vacunación terapéutica podría constituir un nuevo paradigma en el trtamiento contra el VIH.(AU)

Recent findings on the field of antiretroviral treatment intesnsification demonstrate thar the way towards a cure for HIV requires the involvement of novel treatment strategies like therapeutic vaccines. DermaVir therapeutic vaccine includes key technological elements of rational vaccine design: a single plasmid DNA (pDNA) immunogen that expresses 15 HIV antigens, nanomedicine formulation and a unique dendritic cell-targeting topical vaccine administration. Following topical administration on the prepared skin, DermaVir nanomedicine is transported by activated epidermal Langerhans cells to the lymph nodes to express the pDNA-encoded HIV antigens and induce precursor/memory T cells with high proliferation capacity. Safety, immunogenicity and preliminary efficacy of DermaVir have been demonstrated in several animal models and HIV-infected human subjects. This novel therapeutic vaccination technology might offer a new treatment paradigm against HIV.(AU)

Perfil da resposta terapêutica a medicamentos antirretrovirais envolvendo crianças e adolescentes infectados pelo HIV1 no Rio Grande do Sul / Profile of therapeutic response to antiretroviral drug treatment among HIV1?infected children and adolescents in Rio Grande do Sul

No fim da década de 80, muitas mulheres passaram a contrair o vírus HIV e este fato começou a delinear um novo perfil da epidemia da AIDS no Brasil. No entanto, muitos estudos sobre HIV/AIDS são realizados somente com a população adulta e dados sobre a infecção pediátrica ainda são bastante escassos. Este é um estudo transversal que objetiva traçar o perfil da resposta à terapia antirretroviral em uma população formada por crianças e adolescentes. Este trabalho foi desenvolvido por meio da análise dos resultados dos testes de genotipagem - disponíveis no banco de dados do Setor de Biologia Molecular do Laboratório Central do Estado do Rio Grande do Sul (LACEN-RS). Por meio dos testes de genotipagem foi possível observar algumas mutações de resistência aos antirretrovirais. O subtipo B apresentou maior prevalência, seguido pelo subtipo C. As mutações que ocorreram com maior frequência foram D67N e V118I, pertencentes à classe de medicamentos Nucleosídeos Inibidores da Transcriptase Reversa (NRTI). Foi possível observar que alguns medicamentos apresentaram maiores níveis de resistência simples: Zidovudina e Lamivudina. A importância da identificação de mutações de resistência se faz relevante na escolha dos medicamentos que serão utilizados, aumentando assim, as chances de sucesso da terapia.

In the late 80s, many women began to contract the HIV virus; this fact began to change the profile of AIDS epidemic in Brazil. However, many studies of HIV/AIDS are performed only on the adult population and data on pediatric HIV infection are still quite scarce. The aim of this cross-sectional study was to outline the response of the HIV infection to antiretroviral therapy in a population composed of children and adolescents. The work involved analyzing the results of virus genotyping assays, available in the database of the Section of Molecular Biology of the Central State Laboratory of Rio Grande do Sul (LACEN-RS). Subtype B was the most prevalent, followed by subtype C. Through genotyping, it was possible to observe some antiretroviral resistance mutations. The mutations that occurred most frequently were D67N and V118I, which confer resistance to medications of the class of Nucleoside Reverse Transcriptase Inhibitors (NRTI). The highest observed frequencies of resistance were to Zidovudine and Lamivudine. The identification of resistance mutations is of great relevance in the choice of drugs that will be used to treat a particular patient, to maximize the chance of a successful therapy.

Toward preserving the structure of the antigenic peptide p17-1 from the HIV-1 p17 protein in nanostructured films.

Antigenic peptides may be immobilized in nanostructured films in order to build highly specific immunosensors and other devices that require molecular recognition, with no need to use complex molecules. A major challenge for such endeavors, however, is to preserve the secondary structure of the peptides after immobilization. In this study, we show that the peptide p17-1 (LSGGELDRWEKIRLRPGG), derived from the HIV-1 p17 protein, may be immobilized in Layer-by-Layer (LbL) films made with polyelectrolytes. Its structure was preserved only if incorporated into phospholipid liposomes, according to fluorescence and circular dichroism (CD) spectroscopy. The lack of secondary structure for the peptide in the LbL film may be associated with the film-forming procedure in which p17-1 was adsorbed from an aqueous solution, where it does not form alpha helices. The importance of structure preservation was clear in the attempts to produce electrochemical immunosensors with the p17-1 peptide without being protected in liposomes in an LbL film. There was no detectable influence of the presence of anti-p17 antibodies, though some molecular interaction could be inferred from the voltammograms. In contrast, for p17-1 incorporated in liposomes electrochemical immunosensors could be obtained with the voltamogramms showing strong molecular recognition with the antibodies. These results indicated that phospholipids serve as a suitable matrix for immobilization of peptides, and confirmed the importance of structure preservation in electrochemical immunosensors.