From the early 1990s, rates of HIV infection increased dramatically in South Africa and by the early 2000s, AIDS emerged as the main cause of death for adult South Africans. During the first half of the 2000s, the South African government’s response to this crisis was inadequate, marked by denial and delays in implementing prevention and treatment, resulting in thousands of preventable deaths. Yet, apart from the challenges posed by the predominantly urban-based Treatment Action Campaign (TAC), the absence of a social response to this crisis is notable, especially in rural settings. This scenario forms the broad backdrop to this ethnographic study that draws on participant observation and interviews undertaken over a three-year period (2002-2005) in KwaBomba village previously in the Gazankulu Homeland, now located in the Bushbuckridge municipality of the South African lowveld. An ethnographic perspective provides an intimate vantage point from which to view peoples’ experiences of the AIDS epidemic and their responses in context. This perspective draws attention to gaps in public health and biomedical understandings of the epidemic and suggests alternatives to these understandings. In Bushbuckridge, mortality and morbidity due to AIDS became visible in the late 1990s and early 2000s. Households were incapable of dealing with the burden of illness and death while the health services were often unwilling and ill-prepared. HIV prevention campaigns based on individual behaviour change were not well suited to a context in which HIV spread through sexual networks. Despite widespread awareness of the threat of AIDS, the disease was subjected to public censorship and AIDS suffering was concealed. Public discourses of AIDS were hidden within gossip and rumour and articulated as witchcraft suspicions and accusations. Although these discourses appear to deny and suppress the reality of AIDS, I suggest that they are active attempts to deal with the AIDS crisis: gossip and rumour allocate blame and construct a local epidemiology through which the epidemic can be surveilled; interpreting AIDS as witchcraft creates the possibility of avenging untimely death. These discursive forms are critical in informing individual and social responses to the AIDS epidemic. While the absence of public acknowledgement of AIDS as a cause of illness and death suggests denial and fatalism and appears to limit public action, subaltern discourses create shared secrets to manage the AIDS epidemic at the local level. Furthermore, these discourses may constitute a form of resistance against biomedical models of causality. Ethnographic enquiry at the local level offers a nuanced understanding of social responses to the AIDS epidemic. By examining forms of expression that lie outside the domain of public health, the thesis reveals how these constitute significant forms of social action in response to the epidemic. / Thesis (PhD)--University of Pretoria, 2012. / Anthropology and Archaeology / unrestricted

Registered nurses are exposed to the risk of Human Immunodeficiency Virus (HIV) infection and contracting the Acquired Immunodeficiency Syndrome (AIDS). Qualitative phenomenological research was conducted to explore registered nurses' experiences of working in such a high-risk environment and how their experiences influence the therapeutic relationship. A sample of registered nurses who care for HIV-infected persons or persons who suffer from AIDS was purposefully selected. Focus group interviews were conducted. Qualitative data analysis was performed. Frankl's theory of meaning of life served as a theoretical foundation for interpreting the research findings. The research results revealed that registered nurses experience existential frustration due to the intentional and unintentional risks that they are exposed to. This negatively impacts upon their ability to maintain a healthy therapeutic relationship with patients. However, evidence was obtained indicating that some factors support their quest for finding meaning in life in the workplace. / Health Studies / M.A. (Health Studies)

Introdução: com o advento da terapia antirretroviral altamente ativa observou-se um profundo impacto na história natural da infecção pelo HIV. O emprego de combinações terapêuticas contendo drogas de diferentes classes promove importante e sustentada supressão na replicação viral, levando à restauração imunológica e, consequentemente, eleva a sobrevida e a qualidade de vida das pessoas que vivem com HIV (PVH). Objetivos: a presente proposta visa analisar e caracterizar as alterações endocrinológicas e metabólicas associadas ao uso de medicamentos antirretrovirais em PVH e desenvolver algoritmos computacionais inteligentes visando sua identificação e previsão. Métodos: Trata-se de uma coorte ambidirecional de PVH, que iniciaram o uso de TARV entre 1º. de janeiro de 2003 e 31 de dezembro de 2013, com seguimento até dezembro de 2014. Recortes metodológicos foram empregados para, (1) avaliar a qualidade da base de dados, (2) estimar a densidade de incidência de alterações lipídicas e glicídicas na coorte, (3) identificar fatores associados à incidência de diabetes mellitus, e (4) desenvolver um algoritmo para predição de novos casos de diabetes mellitus. O primeiro recorte utilizou as estatísticas de kappa e coeficiente de correlação para medidas qualitativas e quantitativas de LTCD4+ e carga viral do HIV; o segundo usou estatísticas de incidência acumulada com intervalo de confiança de 95% com emprego do método de reamostragem de bootstrap e determinação da densidade de incidência por 1.000 pessoas ano usando, com cálculo de intervalo de confiança de 95% projetado com distribuição de Poisson; o terceiro utilizou a regressão de Cox e um modelo hierarquizado para estudar os fatores que influenciam no tempo até a ocorrência de diabetes mellitus e, o quarto, empregou metodologia para estruturação do sistema especialista fuzzy Sugeno, a curva ROC para estudar a acurácia do modelo comparada aos outros fatores. Resultados: 8.007 pacientes foram considerados elegíveis no primeiro recorte. A correlação geral observada para a menor contagem de LTCD4+ antes de TARV foi 0,970 (p < 0,001). Os coeficientes gerais de concordância para medidas qualitativas de contagens de LTCD4+ e para CV foram, respectivamente, 0,932 (p < 0,001) e -0,996 (p < 0,001). No caso do segundo e terceiro recorte, foram considerados 6.724 pacientes. As alterações metabólicas mais comuns foram a hipertrigliceridemia isolada 84,3 por 1000 pessoas-ano (IC95% 81,1-87,6), seguida por baixas concentrações de HDL-colesterol (HDL-c) 48,5 por 1.000 pessoas-ano (IC95% 46,1-51,1) e diabetes mellitus 17,3 por 1.000 pessoas-ano (IC95% 15,8-18,8). As variáveis mais fortemente associadas à incidência de DM foram idade 40 --| 50 anos HR 1,7 (IC95%1,4-2,1) e >= 50 anos HR 2,4 (IC95%1,9-3,1), obesidade HR 2,1 (IC95%1,6- 2,8), razão triglicerídeos:HDL-c >= 3,5 HR 1,8 (IC95%1,51-2,2) e hiperglicemia HR 2,6 (IC95%1,7-2,5). O sistema fuzzy Sugeno teve acurácia (AUC) de 0,811 (IC95% 0,772- 0,851). Conclusões: as análises indicaram alta correlação (quantitativa) e concordância (qualitativa) entre Coorte Brasil de HIV/AIDS e o sistema informatizado SISCEL; diabetes mellitus e outros alterações metabólicas foram comuns na coorte Brasil de HIV/AIDS; a exposição a estavudina (d4T) mostrou-se fator de risco para diabetes mellitus; e o algoritmo linguístico fuzzy foi capaz de predizer novos casos de diabetes mellitus com acurácia superior à dos fatores de risco convencionais / Introduction: with the advent of highly active antiretroviral therapy (ART) a profound impact on the natural history of HIV infection was observed. The use of combined therapeutic regimens containing antiretroviral drugs of different classes promotes important and sustained suppression of viral replication, leading to immune restauration and increases survival and the quality of life of people living with HIV (PLWH). Objectives: This study aims to analyze and characterize the endocrinological and metabolic changes associated with the use of antiretroviral drugs in PLWH and to develop intelligent computational algorithms for their identification and prediction. Methods: this is an ambidirectional cohort of PLWH, who were started on ART between January 1, 2003 and December 31, 2013, with follow-up through December 31, 2014. Our methodological approaches aimed at (1) assessing the quality of the database, (2) estimating the incidence density of lipid and glucose changes, (3) identifying factors associated with incident diabetes mellitus, and (4) developing an algorithm for prediction of incident diabetes mellitus. For the first approach we used the kappa and correlation coefficient statistics for qualitative and quantitative measures of LTCD4 + and HIV viral load (VL); for the second we used cumulative incidence statistics with a 95% confidence interval, by means of bootstrap resampling and calculation of incidence density per 1,000 person-years with a 95% confidence interval based on the Poisson distribution; for the third we used Cox regression and a hierarchical model to investigate factors that influenced time until incidence of diabetes mellitus and, for the fourth, we used in addition to structuring the Sugeno fuzzy expert system, the ROC curve to assess the accuracy of the model as compared to other factors. Results: 8,007 patients were considered eligible for the first approach; overall observed correlation for the lower LTCD4+ count before ART was 0.970 (p < 0.001) and the general agreement coefficient for qualitative measures of LTCD4 + counts and HIV VL were 0.932 (p < 0.001) and -0.996 (p < 0.001), respectively. For the second and third approaches, 6,724 patients were considered. The most common metabolic alterations were hypertriglyceridemia, 84.3 per 1,000 person-years (95% CI 81.1-87.6), followed by low HDL-cholesterol (HDL-c) 48.5 per 1,000 person-years (95% CI 46.1-51.1) and diabetes mellitus 17.3 per 1,000 person-years (95% CI 15.8-18.8). Most strongly associated factors with incident DM were age 40 - | 50 years HR 1.7 (95%CI 1.4-2.1) and age >= 50 years HR 2.4 (95%CI 1.9-3.1), obesity HR 2.1 (95% CI 1.6-2.8), triglyceride:HDL-c ratio >= 3.5 HR 1.8 (95% CI 1.51-2.2) and hyperglycemia HR 2.6 (95% CI 1.7-2.5). The Sugeno fuzzy system had an accuracy (AUC) of 0.811 (IC95% 0,772-0,851). Conclusions: the analyses indicated a high correlation (quantitative) and agreement (qualitative) between Brazil\'s HIV/AIDS Cohort Study and SISCEL databases; diabetes mellitus and other metabolic alterations were common in the Brazil cohort of HIV / AIDS; exposure to stavudine (d4T) was a risk factor for incident diabetes mellitus; and the fuzzy linguistic algorithm could predict new cases of diabetes mellitus with a higher accuracy than conventional risk factors

O presente trabalho é composto por 4 capítulos distintos. No primeiro intitulado \"Ciclodextrinas: tecnologia para melhoria da solubilidade de fármacos pouco solúveis\" aborda-se uma revisão das ciclodextrinas e de seus derivados, como também a formação dos complexos de inclusão. No segundo capítulo, \"Obtenção e caracterização de complexos ternários de saquinavir, &#946;-ciclodextrina e polivinilpirrolidona\", foram avaliadas condições que poderiam influenciar na obtenção dos complexos, tais como: tempo de agitação na formação dos complexos, proporção equimolar de fármaco e ciclodextrina, solvente para solubilização do fármaco e porcentagem de polímero hidrossolúvel, concluindo-se que as melhores condições para obtenção dos complexos são 48 horas de agitação, razão equimolar 1:2 e 1:4, água para solubilização do fármaco e acréscimo de1% de polímero ao sistema. O terceiro capítulo, \"Influência do método de secagem na obtenção de complexos ternários de saquinavir\", teve o objetivo de obter e caracterizar complexos ternários de saquinavir, &#946;-ciclodextrina e polivinilpirrolidona pelos métodos de secagem em estufa e liofilização, bem como, comparar a influência dos métodos de obtenção na solubilidade do fármaco, chegando-se ao aumento de 44 vezes da solubilidade do fármaco quando na forma de complexo SAQ:&#946;CD:PVP de proporção equimolar 1:2 obtido por liofilização. O quarto, \"Perfil de dissolução de cápsulas e comprimidos contendo complexos ternários de saquinavir, ciclodextrina e polivinilpirrolidona\", teve o objetivo de comparar o perfil de dissolução de cápsulas de gelatina dura e comprimidos contendo sistemas ternários SAQ:&#946;CD:PVP, obtidos pelos métodos de secagem em estufa e liofilização e o produto referência (Fortovase®). Os resultados indicam que os perfis de dissolução das formas farmacêuticas contendo complexos liofilizados apresentaram melhores resultados de eficiência de dissolução e que as cápsulas liberam mais prontamente o ativo que os comprimidos. / The present study has 4 captions. The first is called \"Cyclodextrins: Technology to improve the solubility of the little soluble drugs\" show a review of the cyclodextrins and its derivates, as well the formations of inclusion complexes. At the second caption, \"Preparation and characterization of the ternary complexes of the saquinavir, &#946-cyclodextrin and polyvinylpyrrolidone\", were evaluated some conditions that could influence in an obtention of the complexes like stirring time at the formation of the complexes, equimolar ratio of the drug and cyclodextrin, solvent for the solubility of the drug and percentage of the hydrosoluble polymer concluding that the best conditions for the formation of the complexes are: 48 hours of the stirring, equimolar ratio 1:2 and 1:4, water to solubilize the drug and addition of 1% of the polymer in the system. The third caption, \"Influence of the drying method at the formation of the ternary complexes of the saquinavir\", had the aim to prepare and characterize ternary complexes of the saquinavir, &#946-cyclodextrin and polyvinylpyrrolidone by the method of drying in equipment and lyophilization, as well to compare the influence of the methods of the obtention at the solubility of the drug, reaching the increasing of 44 times the solubility of the drug when at the form of the ternary inclusion complex (SAQ:&#946;CD:PVP) at the equimolar ratio 1:2 obtained by lyophilization. The fourth and the last caption, \"Dissolution rate of the capsules and tablets of ternary complex of the saquinavir, cyclodextrin and polyvinylpyrrolidone, had the aim to compare the dissolution profile of capsules of the hard gelatine and tablets of ternary complexes SAQ:&#946;CD:PVP obtained by the method of drying in equipment and lyophilization and the reference product (Fortovase®). The results indicate that the dissolution profiles of the pharmaceutical forms of lyophilized complexes show better results of the efficience of the dissolution and that the capsules liberate more efficient the active than the tablets.

A infecção pelo vírus da imunodeficiência humana na Amazônia tem-se mostrado como um dos mais recentes desafios para o enfrentamento da epidemia de HIV/aids no Brasil. Estudos epidemiológicos baseados em dados de incidência mostram tendência de crescimento da epidemia na região Norte do país. O Serviço de Assistência Especializada de Santarém é referência em assistência às pessoas com HIV/aids de 25 municípios das mesorregiões do baixo Amazonas e sudoeste do Pará. Os objetivos do presente trabalho consistem em descrever as características sociodemográficas, clínicas e laboratoriais de pessoas vivendo com HIV à admissão nesse serviço de referência, comparando-as entre os períodos: 1999 a 2002(P1), 2003 a 2006(P2) e 2007 a 2010(P3) e analisar as tendências de incidência de aids em Santarém entre 1999 e 2010. As informações referentes às variáveis de interesse foram obtidas em revisão de prontuários. Foram calculados os coeficientes de incidência padronizados a partir dos casos notificados de aids em Santarém, obtidos em bases de dados nacionais e locais. A análise de tendência de incidência foi realizada por modelos de regressão polinomial. A maioria dos 527 sujeitos (62,4%) foi admitida em P3, com 24,1% e 13,5% em P2 e P1, respectivamente. Observou-se aumento significativo da participação de indivíduos não procedentes de Santarém em P3 em comparação a P1. Verificou-se diferença significativa entre os sexos com relação ao motivo de realização da testagem pelo fato do conhecimento da soropositividade do parceiro ter motivado a testagem entre as mulheres em P1 e P2. Enquanto a presença de sinais e sintomas sugestivos de HIV/aids motivou o teste em homens durante todo o período avaliado. Houve redução significativa das medianas de linfócitos T CD4+ à admissão em P3, em relação a P1 e P2. Foram notificados 336 casos novos de aids em Santarém no período de 1999 a 2010. Foi encontrada tendência significativa de crescimento da epidemia em Santarém em ambos os sexos, e nas categorias de exposição ao HIV heterossexual e homo/bissexual no sexo masculino. O crescimento da demanda assistencial no serviço de Santarém, com incremento do número de pacientes procedentes de municípios menores e, admitidos em estadios tardios da infecção, associada à tendência de crescimento de incidência de aids em Santarém no período estudado, sugerem que as intervenções programáticas implementadas na região podem ter contribuído para o reconhecimento de maior número de casos de aids, porém ainda não possibilitaram o diagnóstico mais precoce. Acredita-se que estratégias de vigilância epidemiológica de segunda geração poderiam subsidiar de modo mais eficiente as intervenções programáticas voltadas ao controle da epidemia em uma região caracterizada por apresentar fatores individuais, sociais e programáticos que conferem vulnerabilidade acrescida à infecção pelo HIV. / Infection with human immunodeficiency virus within the Amazon region has been shown as one of the latest challenges confronting the HIV/AIDS epidemic in Brazil. Epidemiological studies based on incidence data show an increasing trend in AIDS incidence in the Brazilian North region. The specialized HIV/AIDS outpatient clinic of Santarém is the reference healthcare setting that provides care for people living with HIV/AIDS (PLHA) from 25 municipalities of the Lower Amazon and southwestern Pará regions. The aims of this study are to describe socio-demographic, clinical and laboratory features of PLHA at time of admission to this reference clinic, comparing them among the following periods: 1999 to 2002 (P1), 2003 and 2006 (P2) and 2007 and 2010 (P3), and to analyze AIDS incidence trends in Santarém between 1999 and 2010. Information about variables of interest was obtained by review of medical records. Standardized AIDS incidence rates were calculated, based on cases reported in Santarém, using data obtained from national and local databases. Incidence trend analysis was performed by polynomial regression. Out of 527 records, 62.4% of patients were admitted to the clinic in P3, 24.1% and 13.5% in P2 and P1, respectively. A significant increase was seen in the participation of individuals from cities other than Santarém in P3, as compared to P1. There was a significant gender difference in the reason to be tested for HIV, as women were more likely to have been tested due to a seropositive partner in P1 and P2, whereas existing signs and symptoms of HIV/AIDS predominated among men as the reason for testing throughout the study period. A significant reduction in median CD4+ cell counts at admission was noticed comparing P3 to P1 and P2. 336 AIDS cases were reported in Santarém from 1999 to 2010. An increasing AIDS incidence trend was found for both genders, and for both heterosexual and homo/bisexual among males. The increasing local demand for HIV/AIDS care, with larger numbers of cases coming from smaller cities and admitted in later stages of HIV infection, taken together with the increasing AIDS incidence trend in Santarém during the study period suggest that even though programmatic interventions may have succeeded in identifying more AIDS cases, they were not able to lead to an earlier diagnosis. We believe that the implementation of second generation surveillance strategies in this region could guide programmatic interventions for the control of the epidemic more efficiently, in a context characterized by individual, social and programmatic factors related to a high vulnerability to HIV infection.

Introdução: O cenário da epidemia da AIDS vem se modificando no Brasil e no mundo e o perfil epidemiológico das pessoas vivendo com HIV/AIDS vem sofrendo sucessivas alterações desde a década de 80. Embora os homens representem em números absolutos, o maior número de notificações do total de casos de AIDS, a velocidade de crescimento da epidemia é maior entre as mulheres. O Brasil tem uma resposta à epidemia de DST/AIDS reconhecida internacionalmente, baseada nos princípios do SUS à universalidade, à equidade e à integralidade na assistência. Um dos capítulos desta resposta é a prevenção da transmissão vertical do HIV. O tema que vem ganhando importância na medida em que a AIDS recebe status de doença crônica e as mulheres soropositivas podem fazer as suas escolhas reprodutivas. A prevenção da transmissão vertical do HIV contempla testagem para diagnóstico precoce, terapia antirretroviral durante a gravidez e o parto, terapia antirretroviral para o recém-nascido e a não amamentação. Objetivo- Conhecer como as ações de prevenção e controle da transmissão vertical do Vírus da Imunodeficiência Humana são percebidas pelas gestantes e puérperas atendidas pelo Programa Estadual de DST/AIDS, e sua satisfação, ou insatisfação, em relação à assistência recebida. Método- Nossa amostra foi composta por 14 mulheres, sendo 13 soropositivas para o HIV que engravidaram e tiveram pelo menos um filho no contexto da soropositividade e uma, soronegativa para o HIV e mãe adotiva de uma criança soropositiva. Para a coleta de dados foi utilizada a metodologia qualitativa, com base em entrevistas individuais, semiestruturadas, realizadas em 2010. Resultados - Não houve aconselhamento para a testagem de nenhuma mulher da amostra. As mulheres apresentaram, no geral, uma falta de identificação com o perfil de pessoas que podem se infectar com o HIV, sendo surpreendidas com o diagnóstico. Oito pais apresentaram status sorológico desconhecido, sendo que três negaram-se à testagem. Há dificuldades por parte das mulheres, para promoverem relações sexuais protegidas com o uso do preservativo masculino. Os efeitos adversos dos antirretrovirais são descritos como obstáculo importante à adesão ao tratamento. O alojamento conjunto foi o cenário das piores vivências dentre toda a assistência recebida, destaque dado ao tema aleitamento materno. Há uma lacuna entre as demandas das mulheres em produzir e relatar as suas narrativas e a inexistência de espaços de escuta, seja individualmente na relação com o profissional médico, seja em grupos. Conclusões - A ausência do aconselhamento como espaço de abordagem e esclarecimentos, informações e escolhas, dificulta uma ação mais oportuna para a redução da transmissão vertical do HIV. As mulheres comuns não são atingidas pelas informações sobre HIV/AIDS oferecidas pelas campanhas para prevenção da infecção. O uso do preservativo para evitar a infecção ainda é uma decisão masculina. As mulheres raramente encontram interlocução entre os profissionais, para tirarem suas dúvidas e planejarem sua vida reprodutiva de forma mais segura. Apesar da falta de discussão sobre o planejamento terapêutico, a via de parto e os cuidados com o bebê, as mulheres seguem a prescrição e seguem com seus medos e suas dúvidas / Introduction: The scenario of the AIDS epidemic has been changing in Brazil and worldwide, and epidemiological profile of people living with HIV / AIDS has undergone successive changes since the 80\'s. Although men represent in absolute numbers, the highest number of notifications of all cases of AIDS, the epidemic growth rate is higher among women. Brazil has a response to the epidemic of STD / AIDS internationally recognized principles of the SUS: universality, equity and integrity in service. One of the elements of this response is the prevention of vertical transmission of HIV. The theme that is gaining importance, as AIDS gets the status of chronic disease and HIV positive women can make their own reproductive choices. The prevention of vertical transmission of HIV includes testing for early diagnosis, antiretroviral therapy during pregnancy and delivery, antiretroviral therapy for the newborn and not breastfeeding. Objective -To study how the prevention and control of vertical transmission of human immunodeficiency virus are perceived by pregnant women and new mothers assisted by the State Program of STD / AIDS, and their satisfaction or dissatisfaction in relation to care received. Methods -Our sample consisted of 14 women, 13 HIV-positive pregnant and who had at least one child in the context of being HIV positive and one was seronegative for HIV and an adoptive mother of an HIV positive child. To collect data we used the qualitative methodology, based on individual interviews, semi-structured, conducted in 2010. Results - There was no counseling for the testing of any women in the sample. Women had, overall, a lack of identification with the profile of people who can become infected with HIV, being surprised by the diagnosis. Eight male partners had unknown HIV status, and three refused to be tested. There are difficulties, for women, to promote safe sex with condom use. Adverse effects of antiretroviral drugs are described as barrier to treatment adherence. Rooming-in was the scene of the worst experiences among all the care received, highlighting the theme of breastfeeding. There is a gap between women\'s demands to produce and report their stories and the lack of opportunities to listen, either individually in relation to the medical professional, either in groups. Conclusions - The lack of counseling as a space for dialogue and explanations, information and choices, hampers a more timely action to reduce vertical transmission of HIV. The \"ordinary\" women are not affected by information about HIV / AIDS provided by the campaigns to prevent infection. The use of condoms to prevent infection is still a male decision. Women are rarely have the opportunity to with professionals, to expose their questions and plan their reproductive lives more safely. In this setting of lack ofparticipation on treatment planning, delivery or baby care, women follow the \"prescription\" and move on with their fears and doubts

by Joe Chan Bing Hang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 48-54). / Abstracts in English and Chinese; questionnaire in Chinese. / ABSTRACT --- p.i / ACKNOWLEDGEMENTS --- p.ii / TABLE OF CONTENTS --- p.iii / Chapter CHAPTER I - --- INTRODUCTION --- p.1 / Chapter CHAPTER II - --- METHOD --- p.23 / Chapter CHAPTER III - --- RESULTS --- p.29 / Chapter CHAPTER IV - --- DISCUSSION --- p.38 / REFERENCES --- p.48 / APPENDIX --- p.55

by Lam Mei Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 127-137). / Abstract also in Chinese. / Acknowledgment --- p.I / Table of content --- p.II / List of figures --- p.VII / List of tables --- p.IX / Abbreviation --- p.X / Abstract --- p.XII / 論文摘要 --- p.XIII / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Acquired immunodeficiency syndrome --- p.1 / Chapter 1.1.1 --- Discovery of AIDS --- p.1 / Chapter 1.1.2 --- Definition and symptoms of AIDS --- p.1 / Chapter 1.1.3 --- AIDS transmission --- p.2 / Chapter 1.1.4 --- AIDS epidemic --- p.3 / Chapter 1.2 --- Human immunodeficiency virus --- p.3 / Chapter 1.2.1 --- Discovery of HIV --- p.3 / Chapter 1.2.2 --- The structure of HIV --- p.4 / Chapter 1.2.3 --- Genomic structure of HIV --- p.5 / Chapter 1.2.4 --- Life cycle of HIV --- p.5 / Chapter 1.2.5 --- How HIV is involved in different stages of AIDS --- p.7 / Chapter 1.3 --- Therapeutic targets for treatment of AIDS --- p.8 / Chapter 1.3.1 --- HIV reverse transcriptase (HIV RT) --- p.8 / Chapter 1.3.2 --- HIV integrase (HIV IN) --- p.11 / Chapter 1.3.3 --- HIV protease (HIV PR) --- p.12 / Chapter 1.3.4 --- Chemokine receptors --- p.14 / Chapter 1.3.5 --- Vaccine development --- p.16 / Chapter 1.4 --- AIDS therapy --- p.17 / Chapter 1.4.1 --- Current status of AIDS therapy --- p.17 / Chapter 1.4.1.1 --- Drugs approved by US Food & Drug Administration (FDA) --- p.17 / Chapter 1.4.1.2 --- Combination therapy --- p.19 / Chapter 1.4.1.3 --- Vaccine development --- p.19 / Chapter 1.4.2 --- Alternative treatment --- p.20 / Chapter 1.5 --- Objective of my project --- p.21 / Chapter Chapter 2 --- Screening of traditional Chinese medicinal (TCM) plants for HIV reverse transcriptase inhibition --- p.22 / Chapter 2.1 --- Introduction --- p.22 / Chapter 2.1.1 --- HIV RT structure and function --- p.22 / Chapter 2.1.2 --- Natural product against HIV RT --- p.25 / Chapter 2.1.3 --- Inhibitory activities from plant extracts --- p.27 / Chapter 2.2 --- Materials and Methods --- p.28 / Chapter 2.2.1 --- Materials --- p.28 / Chapter 2.2.2 --- Extraction methods --- p.30 / Chapter 2.2.2.1 --- Methanol extraction --- p.30 / Chapter 2.2.2.2 --- Hot water extraction --- p.30 / Chapter 2.2.2.3 --- Preparation of Prunella vulgaris extract --- p.30 / Chapter 2.2.3 --- Reverse transcriptase assay --- p.31 / Chapter 2.2.4 --- Characterization of active component in extract of Prunella vulgaris --- p.32 / Chapter 2.2.4.1 --- Protease digestion --- p.32 / Chapter 2.2.4.2 --- Glucosidase digestion --- p.32 / Chapter 2.2.4.3 --- Ethanol precipitation --- p.33 / Chapter 2.2.4.4 --- Sodium periodiate oxidization --- p.33 / Chapter 2.2.4.5 --- Polyvinylpyrrolidone (PVP) Precipitation --- p.34 / Chapter 2.2.4.6 --- Polyamide resin binding --- p.34 / Chapter 2.2.5 --- Purification of Prunella vulgaris extract --- p.34 / Chapter 2.2.5.1 --- Polyamide resin column chromatography --- p.34 / Chapter 2.2.5.2 --- Sephadex LH-20 chromatography --- p.35 / Chapter 2.2.5.3 --- Reverse phase HPLC chromatography --- p.36 / Chapter 2.2.6 --- Characterization of purified Prunella vulgaris extract --- p.37 / Chapter 2.2.6.1 --- Paper chromatography --- p.37 / Chapter 2.2.6.2 --- Acid hydrolysis of extract --- p.37 / Chapter 2.2.6.3 --- Thin layer chromatography --- p.38 / Chapter 2.2.6.4 --- Other assays --- p.39 / Chapter 2.2.7 --- Calculation --- p.40 / Chapter 2.3 --- Results --- p.41 / Chapter 2.3.1 --- Screening of Herbs --- p.41 / Chapter 2.3.1.1 --- Screening of methanol extracts --- p.41 / Chapter 2.3.1.2 --- Screening of hot water extracts --- p.41 / Chapter 2.3.2 --- Characterization of active components in Prunella vulgaris crude extracts --- p.44 / Chapter 2.3.2.1 --- Protease digestion --- p.44 / Chapter 2.3.2.2 --- Glucosidase digestion --- p.44 / Chapter 2.3.2.3 --- Ethanol precipitation --- p.44 / Chapter 2.3.2.4 --- Sodium periodate oxidation --- p.48 / Chapter 2.3.2.5 --- Effect of naturally occurring chemicals on inhibition of HIV RT --- p.48 / Chapter 2.3.2.6 --- Effect of removal of polyphenolic components of aqueous extract on inhibition of HTV RT --- p.51 / Chapter 2.3.3 --- Further purification of active components in aqueous extract of Prunella vulgaris --- p.53 / Chapter 2.3.3.1 --- Absorption chromatography by polyamide resin --- p.53 / Chapter 2.3.3.2 --- The Sephadex LH-20 chromatography --- p.53 / Chapter 2.3.3.3 --- Reverse phase high performance liquid chromatography --- p.56 / Chapter 2.3.3.4 --- Recovery of extract --- p.59 / Chapter 2.3.3.5 --- Inhibition from extract of various steps of purification --- p.59 / Chapter 2.3.4 --- Characterization of purified aqueous extract of Prunella vulgaris --- p.62 / Chapter 2.3.4.1 --- Paper chromatography --- p.62 / Chapter 2.3.4.2 --- Dose response curve --- p.62 / Chapter 2.3.4.3 --- Acid hydrolysis of purified extract --- p.68 / Chapter 2.3.4.4 --- Identification of monosaccharide in purified extract by Thin layer chromatography (TLC) --- p.71 / Chapter 2.3.5 --- Specificity of the purified extract on polymerase inhibition --- p.75 / Chapter 2.3.5.1 --- Inhibition of purified Prunella vulgaris extract on Taq polymerase --- p.75 / Chapter 2.3.5.2 --- Inhibition of purified Prunella vulgaris extract on Superscript II --- p.75 / Chapter 2.4 --- Discussion --- p.79 / Chapter Chapter 3 --- Screening of inhibitory activities from traditional Chinese medicinal (TCM) plants extracts to HIV protease --- p.86 / Chapter 3.1 --- Introduction --- p.86 / Chapter 3.1.1 --- HIV Protease structure and function --- p.86 / Chapter 3.1.2 --- Natural products against HIV Protease --- p.87 / Chapter 3.1.3 --- Plant extracts against HIV Protease --- p.89 / Chapter 3.2 --- Materials and Methods --- p.91 / Chapter 3.2.1 --- Materials --- p.91 / Chapter 3.2.2 --- Expression of HIV protease --- p.92 / Chapter 3.2.2.1 --- Expression and purification of HIV protease --- p.92 / Chapter 3.2.2.2. --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) --- p.94 / Chapter 3.2.3 --- Characterization of HIV protease --- p.95 / Chapter 3.2.3.1 --- HIV protease assay by fluorometric measurement --- p.95 / Chapter 3.2.3.2 --- HIV protease assay by using reverse phase high performance liquid chromatography --- p.96 / Chapter 3.3 --- Results --- p.98 / Chapter 3.3.1 --- Expression of HIV protease --- p.98 / Chapter 3.3.2 --- HIV protease assay --- p.98 / Chapter 3.3.2.1 --- Protease assay by using reverse phase HPLC --- p.98 / Chapter 3.3.2.2 --- Protease assay by fluorometric measurement --- p.98 / Chapter 3.3.3 --- Screening of crude Chinese medicinal extracts on inhibition of HIV protease --- p.104 / Chapter 3.3.3.1 --- Methanol extracts --- p.104 / Chapter 3.3.3.2 --- Water extracts --- p.105 / Chapter 3.3.4 --- Characterization of herbal extracts on inhibition of HIV protease --- p.110 / Chapter 3.3.4.1 --- Dose response curve of methanol extract of Woodwardia unigemmata --- p.110 / Chapter 3.3.4.2 --- Dose response curve of hot water extract of Prunella vulgaris --- p.110 / Chapter 3.3.4.3 --- Inhibition mode of methanol extract of Woodwardia unigemmata --- p.113 / Chapter 3.3.4.4 --- Inhibition mode of hot water extract of Prunella vulgaris --- p.113 / Chapter 3.3.4.5 --- Effect of partially purified extracts on HIV protease inhibition --- p.116 / Chapter 3.4 --- Discussion --- p.119 / Chapter Chapter 4 --- General discussion --- p.124 / References --- p.127 / Appendix / Appendix 1 Pictures of herbs used in this study --- p.i / Appendix 2 Mass spectrometry of purified Prunella vulgaris extract --- p.vi / Appendix 3 Calibration curve for determination of HIV PR concentration --- p.viii

INTRODUÇÃO: No Brasil, mais de 13700 novos casos de aids são registrados em mulheres anualmente, principalmente por transmissão sexual. Na última década, se ampliaram as opções de métodos de prevenção do HIV disponíveis no país baseados no uso profilático de medicamentos antirretrovirais (ARV) por pessoas expostas ao vírus. Questiona-se como dimensões psicossociais, culturais e programáticas da prevenção do HIV interferirão no uso dessas tecnologias. Esta tese busca compreender o processo de decisão e a experiência de uso da profilaxia pós-exposição (PEP sexual) ao HIV por mulheres que buscaram este método preventivo em serviços do Sistema Único de Saúde (SUS). MÉTODOS: Os dados foram coletados como parte de um ensaio clínico pragmático intitulado Estudo Combina!, realizado em serviços de saúde especializados em HIV/Aids localizados em São Paulo, Fortaleza, Ribeirão Preto, Porto Alegre e Curitiba. Foram realizadas observações diretas da oferta da PEP sexual e entrevistas semiestruturadas com mulheres que buscaram a profilaxia nos serviços. A análise dos dados foi guiada por princípios hermenêutico-dialéticos, à luz das teorias construcionistas da sexualidade articuladas ao quadro conceitual da vulnerabilidade e dos direitos humanos (V&DH). As unidades de análise foram as cenas sexuais e as dinâmicas do Cuidado nos serviços de saúde. RESULTADOS: Dezessete mulheres aceitaram participar voluntariamente do estudo. As entrevistadas tinham experiência prévia de uso de preservativo e apenas duas não haviam se protegido nas cenas sexuais que as levaram à PEP. Para as demais, a busca resultou de falha do preservativo em relações que aconteceram em cenários de sexo casual, de trabalho sexual ou de relações sorodiferentes. Nos dois primeiros cenários, a falta intimidade e a indiferença dos parceiros frente ao acidente contribuíram para a decisão das mulheres de buscarem a PEP e contrastaram com a intimidade e a solidariedade que caracterizaram as interações nos cenários de sorodiferença. Quatro entrevistadas conheciam a profilaxia antes do acidente, informadas principalmente por pessoas vivendo com HIV/aids (PVHA), serviços de saúde, profissionais do sexo e internet. Conhecer e usar PEP sexual não resultou na intenção de substituir o uso do preservativo pela profilaxia. As entrevistadas valorizaram a possibilidade de acessar um método eficaz em serviços públicos de saúde, onde se sentiram acolhidas e respeitadas. Aderir ao tratamento profilático exigiu superar efeitos adversos e consequências psicossociais de tomar os ARV, sobretudo o medo de ser discriminada como uma PVHA, que fez com que as entrevistadas mantivessem o uso da PEP sexual em segredo. CONCLUSÕES: Nos diferentes cenários, as cenas sexuais que levaram à PEP foram atravessadas por scripts de gênero e estigmas da sexualidade, que estruturaram a dinâmica das negociações sexuais e as reações das entrevistadas e de seus parceiros frente aos acidentes com o preservativo. O estigma da aids é expressivo nesses cenários que estruturam as experiências de uso da PEP sexual, contribuindo para mantê-la pouco conhecida e dificultando seu uso no cotidiano. Sugerem-se investimentos na divulgação da disponibilidade da PEP sexual no SUS, no aprimoramento da qualificação dos serviços com base no referencial do Cuidado e em intervenções estruturais para mitigar o estigma da aids e a desigualdade de gênero, a fim de promover e proteger os direitos humanos das mulheres, cuja violação produz cenários de maior vulnerabilidade para o HIV / INTRODUCTION: In Brazil, more than 13,700 new cases of AIDS are registered among women annually, due mainly to sexual transmission. In the last decade, the availability of HIV prevention methods based on the prophylactic use of antiretroviral drugs (ARVs) by people exposed to the virus have increased in the country. Questions are raised regarding how psychosocial, cultural and programmatic dimensions of HIV prevention will interfere in the use of these technologies. This thesis aims to understand the decision making process and the experience of using post-exposure prophylaxis after sexual exposure to HIV (nPEP) by women who sought this preventive method in the Brazilian Health System (SUS). METHODS: Data were collected as part of a pragmatic clinical trial entitled Combina! Study, conducted in HIV/AIDS specialized health facilities located in São Paulo, Porto Alegre, Fortaleza, Ribeirão Preto and Curitiba. Direct observations of nPEP services and semi-structured interviews with women seeking the prophylaxis in the facilities were performed. Data analysis was guided by hermeneutic-dialectical principles, oriented by social constructionism theories of sexuality, articulated to the conceptual framework of vulnerability and human rights (V&DH). The units of analysis were the sexual scenes and the dynamics of Care in the health services. RESULTS: Seventeen women voluntarily agreed to participate in the study. Interviewees had previous experience with condoms, and only two had not protected themselves in the sexual scenes that led them to nPEP. For the others, the search resulted from condom failure during sexual intercourses that happened in scenarios of casual sex, sex work or serodifferent relationships. In the first two scenarios, the lack of intimacy with the partners and their indifference to the accident contributed to the women\'s decision to seek nPEP, contrasting with the intimacy and solidarity that characterized the interactions in the serodifference scenarios. Four interviewees were aware of the prophylaxis prior to the accident, mainly informed by people living with HIV/AIDS (PLWHA), health services, sex workers and the Internet. Knowing and using nPEP did not result in the intention to replace condom use with the prophylaxis. The interviewees valued the possibility of accessing an effective prevention method in public health services, where they felt welcomed and respected. Adhering to nPEP required overcoming adverse effects and psychosocial consequences of taking ARVs, especially the fear of being discriminated against as a PLWHA, which made the interviewees keep the use of nPEP in secret. CONCLUSIONS: In the different scenarios, the sexual scenes that led to the nPEP were crossed by gender scripts and stigmas of sexuality, which structured the sexual negotiation dynamics and the reactions of the interviewees and of their partners towards the accidents with the condom. The stigma of AIDS is expressive in these scenarios that structure the experiences of using nPEP, contributing to keep it little known and making its use difficult in daily life. We suggest investments to be made in publicizing the availability of nPEP in the SUS, in improving qualification of nPEP services based on the framework of Care and in structural interventions to mitigate AIDS stigma and gender inequality in order to promote and protect women\'s human rights, which violation produces scenarios of higher vulnerability to HIV

Made available in DSpace on 2016-01-26T12:51:33Z (GMT). No. of bitstreams: 1 andreacarneirodemenezesneves_disset.pdf: 1064515 bytes, checksum: 4e865ffb1b9ab1ee258e16419ad23f48 (MD5) Previous issue date: 2011-07-25 / In Sao Jose do Rio Preto-SP, the current data sum up 3,771 cases of AIDS, with a mortality rate of 1,841. The municipality of Sao Jose do Rio Preto ranks fifth in the number of AIDS cases in the state. Material and method: A retrospective study has been conducted from January 2005 to December 2009. All the HIV-1 seropositive individuals attended by the Testing and Counseling Center were enrolled in the study. Demographic data, epidemiological and clinical data have been analysed: gender, age group, schooling, marital status and co-infection with hepatitis B and C and syphilis. Results: The results showed that the study population was predominately composed of men (74.1%). Men exceed women by 3 to 1. The most frequently age group (70.07%) was between 26-45 years, and 48% of individuals are associated with the category ranging from 8-11 years of schooling. Regarding the single marital status category 60.74% are associated to the subpopulation vulnerable variable, 30.6% and 30.43% of the general subpopulation and chemotherapy dependents, respectively, are associated with couple marital status category. The co-positivity was as follows: HBsAg/HIV, 3.47%; anti-HBc/HIV, 27.2%; and HCV/HIV, 8.39%. The syphilis/HIV screening test was positive in 12.2 %, and the treponema test confirmed 52% of the cases. Conclusion: Co-infections are associated with behavioral factor. These require preventive measures aiming at to reduce the risk and assuring safer sexual practices. Counseling, laboratory testing and distribution of health kits should be incorporated into health services, thus being available to population. / Em São José do Rio Preto-SP, os dados atuais totalizam 3.771 casos de AIDS, com 1826 óbitos, justificando a quinta posição do município no ranking do Estado em casos de AIDS. Método:Foi realizado um estudo retrospectivo, no período de janeiro de 2005 a dezembro de 2009, em que foram incluídos como sujeitos deste estudo todos os indivíduos soropositivos para HIV-1, assistidos no Centro de Testagem e Aconselhamento. Foram analisados dados demográficos, epidemiológicos e clínicos: sexo; faixa etária; escolaridade; estado civil e co-infecção com hepatites B e C e sífilis. Resultados: Os resultados mostraram que a população estudada é composta por indivíduos do sexo masculino (74,1%), a relação gênero masculino/feminino foi de 3:1, a faixa etária de maior frequência (70,07%) foi entre 26-45 anos, 48% dos indivíduos estão associados à categoria de 8 a 11 anos de escolaridade. Na categoria estado civil desunido 60,74% estão associados à variável subpopulação vulnerável, 30,6% e 30,43% subpopulação geral e quimiodependentes, respectivamente, estão associadas à categoria estado civil unido. A co-positividade HBsAg/HIV foi de 3,47%, anti HBc total/HIV foi de 27,2%, HCV/HIV foi de 8,39% e para sífilis/HIV o teste de triagem foi reagente em 12,2% e o teste treponêmico confirmou 52% dos casos.Conclusões: Co-infecções estão associadas a fatores comportamentais, necessitando de ações preventivas voltadas à redução do risco e a práticas sexuais mais seguras. Aconselhamentos, testes laboratoriais e distribuição de insumos devem ser incorporados nos serviços de saúde para que a população tenha acesso.