EFICÁCIA ADAPTATIVA E SITUAÇÕES DE CRISE EM PORTADORES DO VÍRUS HIV IMUNODEFICIÊNCIA HUMANA / AIDS.

O objetivo desta pesquisa foi investigar a eficácia adaptativa e situações de crise de indivíduos portadores do vírus HIV do Programa Municipal DST/AIDS de Aparecida SP. O instrumento utilizado foi a Entrevista Clínica Preventiva - EDAO (Escala Diagnóstica Adaptativa Operacionalizada). Participaram do estudo 5 homens e 5 mulheres que freqüentavam o serviço de saúde. Os resultados do trabalho revelaram que ser portador de uma doença crônica carregada de estigmas como a AIDS é um fator desestruturante para o diagnóstico. Foi percebida na população estudada o comprometimento dos setores afetivo-relacional e produtividade, seguido do sóciocultural. Foram observados alguns aspectos importantes como: a crise do impacto diagnóstico como sendo algo marcante em todos os participantes, bem como o uso de drogas, comportamentos vulneráveis que possivelmente levaram à infecção pelo vírus HIV, dificuldades de resolução de conflitos e nas relações interpessoais, perdas vivenciadas durante toda a vida e também no decorrer da infecção e o fenômeno da feminização do vírus HIV através das mulheres entrevistadas, que foram infectadas por seus parceiros sexuais estáveis. No setor orgânico de funcionamento, a população estudada mostrou adesão ao tratamento A maioria da população estudada foi diagnosticada com adaptação ineficaz severa. Este estudo trouxe questionamentos importantes sobre a maneira com a qual o indivíduo portador do vírus HIV mantém seu equilíbrio psíquico e suas relações com o trabalho que executa, chamando atenção para a necessidade de outros estudos que contemplem diferentes instrumentos para a compreensão do tema.

HIV/AIDS: um perfil epidemiológico do vírus e uma análise das práticas seguras, conhecimento e percepção de mulheres

In recent decades, the debate surrounding the consequences of the HIV has passed by great changes. Earlier, prevention campaigns focused risk groups then risk behaviors and ultimately vulnerability. Furthermore, over the years, the dimensions of HIV that emerged in the social environment are these: internalization, heterosexualization, impoverishment and feminization. Based on these contexts, the composition of this study comprises two papers: the former has the overall objective to analyze the epidemiology and incidence of HIV in Brazilian regions in the period from 1980 to 2012; the latter, it aims to find out whether there is the relationship among safe practices, knowledge and perception of women residents in Manaus and Boa Vista cities on the infection by HIV. In paper 1, it was used information from the Health Ministry, as a data source. Besides, it was developed an exploratory and spatial analysis of incidence rates and relative proportion of notified cases. In paper 2, was used as a source of data, the research "Evaluating the process of spatial and epidemic diffusion of HIV in the federal units of Brazil-Northern Region" in 2008. Furthermore, Statistical Techniques of Cluster Analysis, Analysis of Variance, Chi-Square and Logistic Regression were applied. In this paper, it was found that, in Brazilian Regions, the prevalence of reported cases occurred among heterosexuals in men 20-40 year age group and residing in metropolitan areas. It was observed a significant spatial correlation of the incidence rate of reported cases of HIV. It was also noted by the results that have good knowledge and awareness about HIV does not imply, essentially, in a safe sexual intercourse. These results have shown the need public policies geared to the guiding of society, based in educational strategies aiming both information about the virus and its prevention, as well as public awareness for safe sex practices or in stable or not intercourses

Estudo in silico das interações da protease NS3-NS2B de DENV-2 com o inibidor peptídico Bz-nKRR-H com finalidades terapêuticas

Dengue virus is an important patogen that causes Dengue desease in all world, and belongs to Flavivirus gender. The virus consists of enveloped RNA with a single strand positive sense, 11Kb genome. The RNA is translated into a polyprotein precursor, wich is cleaved into 3 structural proteins (C, prM e E) and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B e NS5). The NS3 is a multifunctional protein, that besides to promote the polyprotein precursor cleavage, also have NTPase, helicase and RTPase activity. The NS3 needs a hydrophilic segment of 40 residues from the transmembrane NS2B protein (who acts like cofator) to realize this functions. Actually, there's no vacines available on the market, and the treatment are just symptomatic. The tetrapeptide inhibitor Bz-Nle-Lys-Arg-Arg-H (Ki de 5,8-7,0 M) was showed as a potent inhibitor μ for NS3prot in Dengue virus. That is a inteligent alternative to treat the dengue desease. The present work aimed analyse the interactions of the ligand bounded to the activity site to provid a clear and depth vision of that interaction. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant = 20 ε and 80 was used. The results demonstrate that the interaction energy of the system reached convergence at 13.5 A. Within a radius of 13,5A the most important residues were identified. Met49, Met84 and Asp81 perform interactions of hydrogen with the ligant. The Asp79 and Asp75 residues present high energy of attraction. Arg54, Arg85 and Lys 131 perform hydrogen interactions with the ligand, however, appear in BIRD graph having high repulsion energy with the inhibitor. The data also emphasizes the importance of residue Tyr161 and the involvement of the catalytic triad composed by Asp75, His51 and Ser135

Drivers of Dengue Within-Host Dynamics and Virulence Evolution

Dengue is an important vector-borne virus that infects on the order of 400 million individuals per year. Infection with one of the virus's four serotypes (denoted DENV-1 to 4) may be silent, result in symptomatic dengue 'breakbone' fever, or develop into the more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Extensive research has therefore focused on identifying factors that influence dengue infection outcomes. It has been well-documented through epidemiological studies that DHF is most likely to result from a secondary heterologous infection, and that individuals experiencing a DENV-2 or DENV-3 infection typically are more likely to present with more severe dengue disease than those individuals experiencing a DENV-1 or DENV-4 infection. However, a mechanistic understanding of how these risk factors affect disease outcomes, and further, how the virus's ability to evolve these mechanisms will affect disease severity patterns over time, is lacking. In the second chapter of my dissertation, I formulate mechanistic mathematical models of primary and secondary dengue infections that describe how the dengue virus interacts with the immune response and the results of this interaction on the risk of developing severe dengue disease. I show that only the innate immune response is needed to reproduce characteristic features of a primary infection whereas the adaptive immune response is needed to reproduce characteristic features of a secondary dengue infection. I then add to these models a quantitative measure of disease severity that assumes immunopathology, and analyze the effectiveness of virological indicators of disease severity. In the third chapter of my dissertation, I then statistically fit these mathematical models to viral load data of dengue patients to understand the mechanisms that drive variation in viral load. I specifically consider the roles that immune status, clinical disease manifestation, and serotype may play in explaining viral load variation observed across the patients. With this analysis, I show that there is statistical support for the theory of antibody dependent enhancement in the development of severe disease in secondary dengue infections and that there is statistical support for serotype-specific differences in viral infectivity rates, with infectivity rates of DENV-2 and DENV-3 exceeding those of DENV-1. In the fourth chapter of my dissertation, I integrate these within-host models with a vector-borne epidemiological model to understand the potential for virulence evolution in dengue. Critically, I show that dengue is expected to evolve towards intermediate virulence, and that the optimal virulence of the virus depends strongly on the number of serotypes that co-circulate. Together, these dissertation chapters show that dengue viral load dynamics provide insight into the within-host mechanisms driving differences in dengue disease patterns and that these mechanisms have important implications for dengue virulence evolution.