引發獲得性免疫缺陷綜合癥（AIDS）的人類免疫缺陷病毒（HIV）是一種逆轉錄病毒。過去的十餘年間，高效抗逆轉錄病毒治療療法（HARRT），在抗病毒感染方面取得了很大的成功。高效抗逆轉錄病毒治療療法是一種將多種抗逆轉錄病毒藥物複合的藥物聯用療法。然而，因為病毒的逆轉錄過程極易突變，導致HIV已經可以對大多數使用的抑製藥物產生抗藥性。因此，有越來越多的需要去尋找新型的抗病毒複製機理，例如將人體細胞蛋白作為載體，來達到克服病毒抗藥性的目的。 / HIV-1的複製離不開宿主細胞的剪接因子，例如SR蛋白。選擇性剪接因子ASF/SF2，一個典型的調控pre-RNA剪接的SR蛋白，在HIV-1的pre-mRNA剪接和複製中起到了很重要的調控作用。ASF/SF2和其他SR蛋白一樣，都被丝氨酸/苏氨酸蛋白激酶（SRPK）磷酸化，磷酸化位點位於C端的丝氨酸/苏氨酸結構域（RS domain）。SRPK通過磷酸化來調節ASF/SF2在細胞中的分佈。對於SRPK 和ASF/SF2複合物的結構學和功能學研究指出，ASF/SF2的docking motif和SRPK1的遠離活性位點的docking groove存在很強的相互作用。而這種相互作用是調節磷酸化過程關鍵。所以，在我們的研究過程中，我們希望通過阻斷2個蛋白的相互作用來干擾ASF/SF2的磷酸化，進而抑制其在HIV-1 pre-mRNA剪接過程中的活性。 / 我們採用以結構為基礎的藥物模擬篩選，來選擇潛在的抑制物，達到通過抑制物與docking groove的相互作用來阻斷ASF/SF2和SRPK1的相互作用，以達到抑制磷酸化的目的。我們使用的數據庫來自于ZINC數據庫（UCSF），包括天然產物數據庫和SPECS。我們採用AutoDock Vina 和AutoDock 4.2 二個模擬軟件來栓選數據庫中351473个化合物。并從中選出50個潛在的化合物用作之後的化學生物學測試。體外的激酶活性試驗顯示，6個化合物對ASF/SF2的磷酸化有抑製作用。 / 體外的HIV-1 pre-mRNA剪接實驗顯示，5個化合物在逆轉錄PCR（RT-PCR）中有一定得抑制效果。和DMSO對照組相比，在抑製劑作用下剪接產物的生成被抑制。HIV-1病毒合胞體感染實驗顯示，有一個化合物對病毒的感染起到了一定的抑制作用。 / 其他的測試實驗還在進行中，包括對SRPK1和抑制物複合物的結構研究，從而更好的研究抑制物的作用機理。以及，採用表面等離子共振波譜來進行動力學研究和其他關於化合物在病毒複製過程中的實驗測試。 / Human immunodeficient virus (HIV) is a retrovirus that cause acquired immunodeficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) is a treatment of HIV infection that uses combinations of antiretroviral drugs and has achieved great success in the past two decades. However, since the reverse transcription process of viral RNA is notoriously prone to error, HIV-1 can acquire resistance to nearly all known inhibitors and has started to develop resistance to HAART. Therefore, there is an ongoing search for new drugs with novel inhibitory mechanism such as targeting cellular proteins essential for HIV-1 replication to overcome drug resistance of the virus. / HIV-1 mRNA undergoes complex splicing and the expression of the integrated HIV-1 provirus is largely dependent on the host’s splicing machinery which assembly requires splicing factors such as serine-arginine rich proteins (SR proteins). Alternative splicing factor/splicing factor 2 (ASF/SF2), a prototypic SR protein that is essential for pre-mRNA splicing, has been shown to play critical roles during HIV-1 pre-mRNA splicing and replication. ASF/SF2, like other SR proteins, is phosphorylated by SR protein-specific kinases (SRPKs) at its C-terminal arginine/serine (RS) domain, which governs its localization and metabolism. Structural and functional studies of SRPK1 in complex with ASF/SF2 has revealed that a docking groove on SRPK1 that is distal to the active site interacts strongly with a docking motif and the RS domain of ASF/SF2, leading to high affinity binding as well as regulating the mechanism of phosphorylation. In this study, we propose that by blocking this interaction, we might interfere the phosphorylation of ASF/SF2 and inhibit its activity during splicing of HIV-1 pre-mRNA. / Structure-based in silico screening method is adopted to identify potential inhibitors that bind to the docking groove of SRPK1 to block the binding and phosphorylation of ASF/SF2. The compound libraries being used include the Natual Products Database and SPECS database from ZINC (UCSF). 351,473 compounds have been screened using the program Autodock Vina as well as Autodock 4.0. Until now 50 potential candidates of inhibitor have been selected for biochemical analyses. In vitro kinase assays showed that six compounds exhibit inhibitory activity against the phosphorylation of ASF/SF2. / To test the effect of the selected inhibitors on the splicing of HIV-1 mRNA, ex vivo splicing assay has been performed. Current results showed that the synthesis of splicing products extracted from drug-treated cells was less efficient when compared to untreated cells. Biological assays testing the inhibitory effects of the compounds on viral infection are currently underway. Our preliminary result suggested that one of the compounds could indeed inhibit HIV-1 viral infection. / Other biochemical and biological analyses including structural study of kinase-inhibitor complexes to understand the mode of inhibition; measurement of binding kinetics using surface plasmon resonance spectroscopy (SPR); and biological assays testing the inhibitory effects of the compounds on replication are underway. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Yu, Xiyao. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 95-107). / Abstracts also in Chinese. / Abstract --- p.I / 摘要 --- p.III / Acknowledgements --- p.V / TABLE OF CONTENTS --- p.VI / LIST OF FIGURES --- p.IX / LIST OF TABLES --- p.XI / Chapter Chapter I --- : Introduction --- p.1 / Chapter 1.1 --- HIV, HAART and HIV Drug Resistance --- p.2 / Chapter 1.2 --- HIV-1 alternative splicing mechanism --- p.9 / Chapter 1.3 --- SR Protein Family --- p.13 / Chapter 1.4 --- Functional roles of SR protein in HIV pre-mRNA splicing --- p.16 / Chapter 1.5 --- Phosphorylation States of SR Proteins --- p.18 / Chapter 1.6 --- SR protein Kinase --- p.20 / Chapter 1.7 --- Interaction between SRPK1 and ASF/SF2 --- p.23 / Chapter 1.8 --- IDC16 and SPRIN340 --- p.26 / Chapter 1.9 --- Structure-based drug screening --- p.27 / Chapter 1.10 --- AutoDock Suite --- p.29 / Chapter 1.11 --- Kinase-substrate interaction inhibitors --- p.30 / Chapter 1.12 --- Focus of study --- p.34 / Chapter Chapter II --- : Materials and Methods --- p.35 / Chapter 2.1 --- Materials --- p.36 / Chapter 2.1.1 --- Bacterial strain --- p.36 / Chapter 2.1.2 --- Antibodies --- p.36 / Chapter 2.1.3 --- Cell line --- p.36 / Chapter 2.1.4 --- Plasmid --- p.36 / Chapter 2.1.5 --- Reagents --- p.38 / Chapter 2.2 --- Expression and purification of Recombinant protein --- p.38 / Chapter 2.3 --- In silico screening of inhibitors --- p.44 / Chapter 2.4 --- Kinase Glo Assay --- p.45 / Chapter 2.5 --- In vitro kinase assay --- p.45 / Chapter 2.6 --- Cell Culture --- p.46 / Chapter 2.7 --- MTT Assay --- p.46 / Chapter 2.8 --- Immunocytochemistry --- p.47 / Chapter 2.9 --- Ex vivo splicing assay --- p.47 / Chapter 2.10 --- Surface plasmon resonance spectroscope --- p.48 / Chapter Chapter III --- : Results --- p.50 / Chapter 3.1 --- In silico screening of inhibitors --- p.51 / Chapter 3.2 --- Selected Compounds Inhibits SRPK1 in Vitro --- p.60 / Chapter 3.2.1 --- Protein purification --- p.60 / Chapter 3.2.2 --- Inhibits ASF/SF2 Phosphorylation by SRPK --- p.66 / Chapter 3.3 --- Surface Plasmon Resonance Binding Competition Assay --- p.76 / Chapter 3.4 --- Inhibitors Alters HIV-1 Alternative Splicing ex Vivo --- p.79 / Chapter 3.5 --- Cytotoxic effect of candidate compound on HeLa cells --- p.84 / Chapter 3.6 --- Nature compound alters ASF/SF2 localization --- p.86 / Chapter Chapter IV --- : Discussion and Conclusion --- p.89 / References --- p.95

介紹 / 愛滋病在中國男男性行為者中的流行持續增長，而新感染HIV的男男性行為者扮演著重要角色。本民族志研究採用了社會生態模式來探討與新感染HIV的男男性行為者中HIV二代傳播、心理健康、以及使用健康服務相關的問題。研究方法包括深入訪談、焦點小組訪談、非正式訪談和參與觀察。此外還採訪了志願者和醫護人員。資料分析採用主題內容分析法。 / 結果 / 在確診為HIV呈陽性後，大多數的男男性行為者經受過一定程度的心理及精神上的問題。與HIV相關的緊張性刺激影響著他們適應這個確診。HIV與一些重要的心理、社會和文化的條件呈現一種綜合流行。而大多數的男男性行為者通過自身的應變能力逐漸康復，其中一些人甚至體驗到某種程度的成長。人的應變能力是一種基於個人與環境互動的建構。 / 11名（占24.4%）HIV呈陽性的男男性行為者報告發生過無保護的肛交行為。基於性伴侶的不同類型，與無保護肛交行為相關的因素則有所不同。這些無保護的肛交行為往往同時伴隨著物質濫用、對風險的錯誤認識、以及消極的情緒或者心理和精神問題。阻礙無保護肛交行為發生的積極因素包括社會支援、自我保健、自我保護和志願服務。 / 自上而下的公共衛生服務傾向於控制和檢測而不是賦權于男男性行為人群，並且在很大程度上忽視了新感染HIV的男男性行為者的心理和精神健康、性健康、以及自我保健的能力。新感染HIV的男男性行為者的未滿足的需求已經被識別，且他們更願意到男男性行為人群的社區，尤其是感染者小組那裏去尋求服務和支援。但男男性行為人群的草根組織卻缺乏資金和技術的支持。 / 結論 / 新感染HIV的男男性行為者所遭遇的問題都植根於特定的個人際遇以及他們所生活的社會生態系統。是時候採取一種廣泛而綜合的“健康同志社區的觀點、促進自我保健的策略、以及具有文化敏感性和社會效能的措施來預防HIV的二代傳播以及促進新感染HIV的男男性行為者的社會福祉。人類行為的非線性的特徵要求愛滋病健康行為研究從強調生物行為的範式轉移到著重愛滋病的社會根源的範式中來。 / Introduction / Newly diagnosed HIV positive men who have sex with men (NHIVMSM) play an important role in accelerating the high HIV prevalence in China. This ethnographic study, employing a modified social ecological model integrating concepts of adaptation, cognition, affect and action, investigated the inter-related issues on secondary HIV transmission, mental health and services utilization in this population. Methodologies included in-depth interviews, focus groups, informal interviews and participant observations. Moreover, information was also obtained from volunteers and health care workers. Thematic content analysis was performed. / Results / Most respondents commonly experienced psychological or mental health problems (e.g. depressive symptoms and anxiety) after their HIV diagnosis. HIV stressors, such as constraints of being HIV positive, limited information and knowledge of HIV/AIDS, ART and its side effects, associated co-morbidities and significant costs in health care, appeared to shape their adaptation to the diagnosis. Moreover, a syndemic was apparent among NHIVMSM and some influential psycho-social and cultural conditions, such as adversities in their migrants’ life, social suffering as MSM, cultural trauma, stigma and discrimination. Most respondents drew on a range of personal resilience strategies and some respondents testified to have achieved post-traumatic growth. Resilience was presented within a person-situation interactional construct. / Eleven (24.4%) respondents reported practicing unprotected anal intercourse (UAI). Several respondents reported their UAI had occurred in the first few months after their diagnosis when they suffered considerably from uncertainty, perceived stigma and identity struggles. Factors associated with UAI were based on differing partner types, such as fear of losing partners in a context of non-serostatus disclosure in lovers or stable partners, tongzhi (gay) sauna setting and moral judgment in casual partners, and poor economic status in commercial partners. UAI usually happened simultaneously in context of substance use, risk misconceptions, encountering negative emotion or mental health problems. Positive factors against UAI included social support, self-care, self-protection and volunteerism. / The current top-down public health services tended to operate on control and surveillance instead of empowering MSM. This approach largely ignored psychological and mental health, sexual health and self-care capacities among NHIVMSM, whose unmet needs were identified as preferring to obtain services and support from MSM and/or PLWH communities. However, current MSM organizations lacked funding and technical support. Health care providers operated with suboptimal care protocols, training and technical support. Coordination and collaborations among health care institutes and MSM communities were relatively weak. Tailored participatory health care is warranted, such as volunteerism, greater involvement of PLWH, health navigators and building supportive environment and services. / Conclusions / The problems of psychological and mental health, risky sexual behavior (UAI) and health services utilization that NHIVMSM encountered resulted from interactions between personal experiences and the social ecological systems they inhabited. Recommendation drawn include adopting a comprehensive and inclusive “healthy MSM community“ approach and a strategy of facilitating self-care to carry out culturally sensitive and socially effective measures to prevent secondary HIV transmission and to promote wellbeing among NHIVMSM. An emerging theoretical implication is that the nonlinearity of human behaviour requires paradigm shifting from a bio-behavioural emphasis to the social origin of HIV/AIDS. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Li, Haochu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 425-457). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; appendixes includes Chinese. / Abstract (English) --- p.iv / Abstract (Chinese) --- p.vii / Acknowledgements --- p.ix / Table of Contents --- p.xi / List of Tables and Figures --- p.xv / Glossary --- p.xvi / Abbreviation --- p.xviii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Background --- p.1 / Chapter 1.1.1 --- High HIV prevalence and incidence among MSM in China --- p.1 / Chapter 1.1.2 --- Social and cultural environment faced by HIV positive MSM --- p.3 / Chapter 1.2 --- Sexual risk and secondary HIV transmission among HIV positive (and newly diagnosed) MSM --- p.7 / Chapter 1.3 --- Psychological and mental health among HIV positive (and newly diagnosed) MSM --- p.10 / Chapter 1.4 --- Health service utilization among HIV positive (and newly diagnosed) MSM --- p.13 / Chapter 1.5 --- Exploring complexities of secondary HIV transmission through qualitative studies --- p.14 / Chapter 1.6 --- Theories, concepts and the research framework --- p.15 / Chapter 1.6.1 --- Conceptualization of adaptation in medical anthropology --- p.15 / Chapter 1.6.2 --- The social ecological model --- p.17 / Chapter 1.6.3 --- Cognitive adaptation and self-control --- p.19 / Chapter 1.6.4 --- Emotion and motivation are influential in health behaviour --- p.21 / Chapter 1.6.5 --- Action world and its role in health behaviour --- p.24 / Chapter 1.6.6 --- Social control/social order --- p.26 / Chapter 1.6.7 --- Stigma --- p.27 / Chapter 1.6.8 --- Identity control --- p.29 / Chapter 1.6.9 --- Research framework --- p.32 / Chapter 1.7 --- Goals, objectives and research questions --- p.34 / Chapter Chapter 2 --- Methodology --- p.38 / Chapter 2.1. --- Entrée into the field --- p.38 / Chapter 2.1.1 --- The start of the research --- p.38 / Chapter 2.1.2 --- Pilot work --- p.39 / Chapter 2.2 --- The participants --- p.43 / Chapter 2.3 --- Data collection --- p.50 / Chapter 2.4 --- Data analysis --- p.58 / Chapter 2.5 --- Rigour --- p.62 / Chapter 2.6 --- Reflexivity --- p.68 / Chapter 2.7 --- Ethical considerations --- p.75 / Chapter Chapter 3 --- Social circumstances and MSM communities in Shenzhen --- p.78 / Chapter 3.1 --- Population and economic circumstances --- p.78 / Chapter 3.2 --- Shifting political situation --- p.80 / Chapter 3.3 --- A migrant society --- p.87 / Chapter 3.4 --- Shenzhen Culture --- p.93 / Chapter 3.5 --- MSM community and tongzhi subculture --- p.98 / Chapter 3.6 --- The subgroup of HIV positive MSM --- p.113 / Chapter 3.7 --- Public health implications --- p.117 / Chapter Chapter 4 --- Health care system and services related to HIV case detection and follow up --- p.118 / Chapter 4.1 --- Formal health care system --- p.118 / Chapter 4.2 --- Health insurance --- p.125 / Chapter 4.3 --- “Four Free and One Care“ policy --- p.126 / Chapter 4.4 --- Informal health care --- p.127 / Chapter 4.5 --- Services related to HIV case detection and follow up --- p.131 / Chapter Chapter 5 --- Psychological and mental health --- p.142 / Chapter 5.1 --- Negative mental health outcomes --- p.142 / Chapter 5.1.1 --- Depressive symptoms --- p.142 / Chapter 5.1.2 --- Anxiety symptoms --- p.146 / Chapter 5.1.3 --- Factors associated with negative mental health outcome --- p.150 / Chapter 5.1.3.1 --- Individual factors --- p.150 / Chapter 5.1.3.2 --- Interpersonal factors --- p.157 / Chapter 5.1.3.3 --- Cultural factors in community and family --- p.160 / Chapter 5.1.3.4 --- Institutional and structural factors --- p.163 / Chapter 5.2 --- Positive mental health outcomes --- p.166 / Chapter 5.2.1 --- Integrating negative experiences and recovery --- p.166 / Chapter 5.2.2 --- Resources for recovery --- p.169 / Chapter 5.2.3 --- Back to normal functioning --- p.170 / Chapter 5.2.4 --- Post-traumatic growth --- p.172 / Chapter 5.2.5 --- Factors associated with positive mental health outcome --- p.175 / Chapter 5.2.5.1 --- Individual factors --- p.175 / Chapter 5.2.5.2 --- Interpersonal factor --- p.181 / Chapter 5.2.5.3 --- Community-related factors --- p.184 / Chapter 5.2.5.4 --- Institutional factors --- p.187 / Chapter 5.3 --- Public health concern of suicidal ideation --- p.190 / Chapter 5.4 --- Impacts of psychological and mental health --- p.194 / Chapter 5.5 --- Summary of psychological and mental health in a modified socio-ecological mode --- p.195 / Chapter 5.6 --- Discussion --- p.197 / Chapter 5.6.1 --- The emerging of a syndemic in HIV and some psycho-social and cultural conditions --- p.197 / Chapter 5.6.2 --- Powerful social and cultural factors associated with mental health --- p.200 / Chapter 5.6.3 --- Resilience among newly diagnosed HIV positive MSM --- p.208 / Chapter 5.6.4 --- Service implications --- p.213 / Chapter Chapter 6 --- Sexual risk --- p.221 / Chapter 6.1 --- Continued unprotected anal intercourse (UAI) after being diagnosed HIV positive --- p.221 / Chapter 6.2 --- Changes in practising UAI during the study period --- p.222 / Chapter 6.3 --- Factors associated with UAI with non-commercial sex partners --- p.224 / Chapter 6.3.1 --- Individual factors --- p.225 / Chapter 6.3.2 --- Interpersonal factors --- p.229 / Chapter 6.3.3 --- Community-based factors --- p.231 / Chapter 6.3.4 --- Institutional factors --- p.234 / Chapter 6.4 --- UAI with commercial sex partners --- p.235 / Chapter 6.5 --- Comparing factors associated with UAI among commercial and non-commercial partners --- p.238 / Chapter 6.6 --- Reduced risky behaviour after diagnosis --- p.239 / Chapter 6.7 --- Factors associated with condom use --- p.241 / Chapter 6.7.1 --- Individual factors --- p.241 / Chapter 6.7.2 --- Interpersonal factors --- p.246 / Chapter 6.7.3 --- Community factors --- p.248 / Chapter 6.8 --- Other special issues related to risky sexual behaviour --- p.250 / Chapter 6.9 --- Summary of sexual risk in a modified socio-ecological model --- p.261 / Chapter 6.10 --- Discussion --- p.263 / Chapter 6.10.1 --- Prevalence of UAI --- p.263 / Chapter 6.10.2 --- Partner types and UAI --- p.265 / Chapter 6.10.2.1 --- Fear of losing partners in a context of non-serostatus disclosure --- p.266 / Chapter 6.10.2.2 --- Anonymous sexual encounters and moral judgment --- p.267 / Chapter 6.10.2.3 --- Economic barriers --- p.270 / Chapter 6.10.2.4 --- Intrapersonal contexts --- p.271 / Chapter 6.10.3 --- Critical views on some practices --- p.274 / Chapter 6.10.4 --- Emerging positive experiences from Shenzhen --- p.276 / Chapter 6.10.5 --- Service implications --- p.279 / Chapter Chapter 7 --- Health service seeking --- p.285 / Chapter 7.1 --- Problems identified in health service seeking --- p.285 / Chapter 7.2 --- Processes of adaptation --- p.289 / Chapter 7.3 --- Negative factors associated with health service seeking --- p.296 / Chapter 7.3.1 --- Individual factors --- p.296 / Chapter 7.3.2 --- Interpersonal factors --- p.302 / Chapter 7.3.3 --- Community-based factors --- p.304 / Chapter 7.3.4 --- Health care institution-based factors --- p.309 / Chapter 7.4 --- Positive factors associated with health service seeking --- p.319 / Chapter 7.4.1 --- Individual factors --- p.319 / Chapter 7.4.2 --- Interpersonal factors --- p.321 / Chapter 7.4.3 --- Community-based factors --- p.325 / Chapter 7.4.4 --- Factors in the health care institutes--free services --- p.328 / Chapter 7.5 --- Summary of health service seeking in a modified socio-ecological model --- p.329 / Chapter 7.6 --- Discussion --- p.331 / Chapter 7.6.1 --- Problems in health care institutes --- p.331 / Chapter 7.6.1.1 --- The top-down approach -- controlling instead of community building --- p.331 / Chapter 7.6.1.2 --- Problems among health care providers --- p.335 / Chapter 7.6.2 --- Tailored participatory approach to health care and education for HIV positive MSM --- p.339 / Chapter 7.6.3 --- Necessity for developing MSM communities --- p.342 / Chapter 7.6.4 --- Service implications --- p.349 / Chapter Chapter 8 --- Discussion and implications --- p.355 / Chapter 8.1 --- The occurrences of UAI and its hidden meaning --- p.355 / Chapter 8.2 --- Informing the future HIV epidemic among MSM in Shenzhen --- p.357 / Chapter 8.3 --- Difficulties of controlling the HIV epidemic among MSM --- p.361 / Chapter 8.4 --- New HIV prevention approach --- p.368 / Chapter 8.5 --- Critiquing theories for recommended changes --- p.386 / Chapter 8.6 --- Limitations of the study --- p.400 / Chapter 8.7 --- Conclusion --- p.405 / Appendix I to IX --- p.409 / Bibliography --- p.425

HIV, syphilis, malaria, and anaemia are major causes of adverse pregnancy outcomes in sub-Saharan Africa (SSA). Despite global and national policies advocating for screening of these conditions, only HIV testing has achieved good coverage, precluding early detection and appropriate management in pregnancy. Rapid pointof-care tests (POCTs) provide an opportunity to integrate diagnosis and provide timely treatment of these conditions in rural antenatal care (ANC) settings. After an introductory chapter, a review of the literature on these four conditions in pregnancy is presented with a focus on SSA. The thesis then shifts attention to Kenya, a country that embodies many of the disease challenges and health system characteristics of the region. Kenyan ANC policy recommends testing for HIV, syphilis and anaemia and preventive strategies for malaria. The following chapters are comprised of three linked studies conducted in western Kenya, that use different methods to progressively investigate the implementation success of integrated point-of-care testing (POCT) for HIV, syphilis, malaria and anaemia at seven peripheral dispensaries. Baseline data confirmed that testing requirements for syphilis, malaria and anaemia are not currently met at dispensary level. We implemented an intervention where test kits were supplied and training plus supervision were provided to enable healthcare workers to conduct integrated POCT for pregnant women. Adoption and fidelity were measured quantitatively using exit interviews, antenatal registers and proficiency scores (Study 1: Integrating point-of-care testing (POCT) for HIV, syphilis, malaria and anaemia in antenatal care at dispensary level in western Kenya: an implementation study) while acceptability, appropriateness and feasibility were assessed qualitatively (Study 2: Exploring healthcare workers and pregnant women’s perspectives on appropriateness, acceptability and feasibility of integrating point-of care testing: A qualitative study). Our findings show that the innovation was highly adopted, meaning almost all pregnant women received the essential tests. This was supported by the qualitative findings where healthcare workers and pregnant women found the innovation acceptable and appropriate. However, fidelity to clinical management guidelines can still be improved. Our qualitative findings provide some explanation for these gaps. One common sentiment among interviews with healthcare workers was that workload was perceived to be a barrier to providing quality care. We explored this further with discrete-event simulation modelling (Study 3: Investigating the operational impact of integrating HIV, syphilis, malaria and anaemia point-of-care testing in antenatal care clinics in western Kenya: a discrete event simulation model) and found the healthcare workers were actually under-utilized. This suggests that nurses should, in theory, have sufficient time to deliver essential ANC services. While integrating POCT addresses one gap, additional interventions to support and supervise healthcare workers are needed to ensure appropriate and high quality of care. An integrated approach to health systems strengthening and more investment in implementation and translation research using multi-methods are needed.

A magnitude e as modificações resultantes da epidemia de Aids no Brasil levaram o Ministério da Saúde a recomendar, a partir de 2001, a incorporação do diagnóstico sorológico da infecção pelo HIV em serviços de atenção básica da rede pública de saúde, visando a universalidade e a ampliação do acesso da população a esses exames. O processo diagnóstico, no caso da AIDS, envolve para além da simples disponibilização da testagem; cobre demandas de prevenção, profilaxia, tratamento e referências adequadas para o interior do sistema assistencial. O estudo realizado teve por objetivo investigar como vem se dando a oferta deste diagnóstico, previsto de estar acontecendo acompanhado de aconselhamento pré e pós-teste, usando como lócus um conjunto de serviços da rede básica de saúde no Município do Rio de Janeiro. Do tipo descritivo-analítico, o trabalho utilizou-se de uma abordagem metodológica qualitativa, realizando entrevistas semi-estruturadas com vinte e dois profissionais de saúde de diversas categorias, envolvidos nos processos de testagem anti-HIV, e com três gestores, buscando compreender como vem sendo ofertado esse cuidado em saúde. O exame do material obtido permitiu a identificação das seguintes categorias analíticas: oferta do teste na rede de atenção básica e dilemas relacionados a esse processo; ações de aconselhamento que acompanham a testagem; resultados do teste anti-HIV e dificuldades na sua comunicação aos usuários; dimensões estrutural e organizacional e gestão do processo de testagem; capacitação dos recursos humanos. Identificou-se que o processo de oferta do teste anti-HIV se circunscreve frequentemente à representação da doença e é necessária maior interlocução na relação profissional de saúde/usuário, considerando a intersubjetividade dos sujeitos envolvidos. Este processo diagnóstico demanda técnicas como apoio, acolhimento e escuta qualificada das necessidades de saúde, entendidas para além das queixas biológicas dos sujeitos, que nem sempre estão se fazendo presentes nos serviços de atenção investigados. Como desafio premente na oferta do diagnóstico anti-HIV, destaca-se que o aconselhamento deve ser uma ferramenta utilizada e reforçada no contexto dos serviços de saúde que atendem pacientes com DST/Aids. Outro desafio, além da capacitação qualificada dos recursos humanos envolvidos, é necessidade de permanente avaliação do processo de oferta que vem sendo oferecido nos serviços da rede básica, que possibilite repensar as atividades de prevenção, o acolhimento e a escuta, e o compartilhamento de idéias entre profissionais que atuam no cotidiano das unidades de saúde e os gestores locais. A pluralidade de questões no fazer em saúde exige que os serviços de saúde e seus responsáveis promovam novos arranjos para que a oferta do teste anti-HIV, como ação de saúde, seja realizada com base na humanização, na integralidade e no respeito aos direitos de cidadania, contribuindo para que a melhoria do atendimento na rede básica se concretize com qualidade.

Made available in DSpace on 2014-07-29T15:25:16Z (GMT). No. of bitstreams: 1 Dissetacao_marislei.pdf: 1330253 bytes, checksum: 79323fee18b3f3953180f7217a8dfe40 (MD5) Previous issue date: 2011-02-21 / Adherence to antiretroviral therapy reduces the risk of treatment failure, toxicity and resistance, so the therapeutic monitoring is necessary in the treatment of infection by human immunodeficiency virus. The aim of this study was to determine, through clinical and laboratory studies, the compliance of individuals sickened by HIV / AIDS with antiretroviral therapy before and after three nursing interventions. The study design was analytical, descriptive, prospective and quantitative, using data from medical records, interviews and blood sampling for plasma levels of efavirenz by HPLC analysis, including subjects with a diagnosis of HIV / AIDS, attended at the Hospital for Diseases Tropical Goiânia - Goiás and treated with zidovudine/ lamivudine and efavirenz. The results of analysis of data from 15 subjects indicate a socio-demographic profile, predominantly male, young, heterosexual. After nursing intervention, there was a change in 48% of the diagnoses. We also noticed a positive change in the rates of CD4, corresponding to 14%. As viral count, an increase of subjects with undetectable loads of 1 st to 2 nd nursing intervention (20%, or 73.3% to 93.3%). Chromatographic analysis of plasma of the subjects indicated that 60% of them had adequate medication adherence, and 40% increased adhesion between the 1st and 2nd visits by nurses, 10% between the 1st and 3rd and 10% between the 2nd and 3rd queries. The factor that was associated with high concentration rate after adjustment in nursing diagnoses and prescriptions was having difficulty using the antiretroviral in the same time. It was also demonstrated significant difference between mean plasma concentrations of efavirenz from the 1st, 2nd and 3rd interventions. Considering the reference measurement of plasma concentrations of efavirenz, the method of accession had a sensitivity and specificity, with high proportion of agreement between the rate of CD4, nursing diagnosis and analysis of the plasma of subjects. Conclusions: the systematization of nursing care and determination of plasma concentrations should be incorporated into the routine outpatient care, for better monitoring of adherence to antiretroviral therapy of individuals sickened by HIV / AIDS. / A adesão à terapia antirretroviral reduz o risco de falha terapêutica, toxicidade e resistência, por isso a monitoração terapêutica é necessária no tratamento da infecção por vírus da imunodeficiência humana. O objetivo deste estudo foi verificar, por meio de estudos clínicos e laboratoriais, a adesão de sujeitos adoecidos por HIV/AIDS à terapia antirretroviral, antes e depois de três intervenções de enfermagem. O estudo foi do tipo analítico, descritivo, prospectivo e quantitativo, utilizando dados dos prontuários, entrevistas e coleta de sangue para dosagens plasmáticas de efavirenz por meio de análise cromatográfica, incluindo sujeitos com diagnóstico para HIV/AIDS, atendidos no ambulatório do Hospital de Doenças Tropicais de Goiânia Goiás e tratados com zidovudina/lamivudina e efavirenz. Os resultados da análise dos dados dos 15 sujeitos indicam um perfil sócio-demográfico, predominantemente masculino, jovem, heterossexual. Após intervenção de enfermagem, houve uma alteração em 48% dos diagnósticos de enfermagem. Observou-se também alteração positiva das taxas de CD4, correspondendo a 14%. Quanto a contagem viral, houve aumento de sujeitos com carga indetectável da 1ª para a 2ª intervenção de enfermagem (20%, ou seja, de 73,3% para 93,3%). A análise cromatográfica dos plasmas dos sujeitos indicou que 60% deles apresentaram adequada adesão ao medicamento, sendo que em 40% aumentou a adesão entre a 1ª e a 2ª consultas de enfermagem, 10% entre a 1ª e a 3ª e 10% entre a 2ª e a 3ª consultas. O fator que se mostrou associado à alta taxa de concentração depois do ajuste nos diagnósticos e prescrições de enfermagem foi ter dificuldades em usar o antirretroviral sempre no mesmo horário. Também foi demonstrada diferença significativa entre as médias das concentrações plasmáticas de efavirenz entre a 1ª, a 2ª e a 3ª intervenções. Considerando referência a mensuração da concentração plasmática do efavirenz, o método da adesão apresentou sensibilidade e especificidade, sendo alta a proporção de concordância entre a taxa de CD4, os diagnósticos de enfermagem e a análise do plasma dos sujeitos. Conclusões: a sistematização da assistência de enfermagem e a dosagem das concentrações plasmáticas devem ser incorporadas à rotina de atendimento ambulatorial, para um melhor acompanhamento da adesão à terapia antirretroviral de sujeitos adoecidos por HIV/AIDS.

De 12 casos de leishmaniose tegumentar (LT) em AIDS, em São Paulo, sete do levantamento retrospectivo (1990 a 2001) e cinco do prospectivo (2001 a 2004), com contato prévio com área endêmica para leishmanioses, 50% eram usuários de drogas injetáveis (1990-2001). Apresentavam média de linfócitos T CD4+ de 77 células/mm3, um era C2 e 11, C3 (classificação de HIV, segundo CDC) e 70% tinha sorologia positiva para leishmanioses. As manifestações de LT em mucosa e pele eram diversificadas: úlcera única ou lesões múltiplas e polimórficas ou disseminadas, incluindo comprometimento genital em 4 casos. Todos receberam tratamento específico para leishmaniose e 50%, HAART. 50% recidivaram e 50% foram a óbito no período, independentemente do uso do HAART / From 12 cases of tegumentary leishmaniasis (TL) in AIDS, from São Paulo, seven from retrospective (1990 a 2001) and five from prospective studies (2001 a 2004), with previous contact with endemic areas for leishmaniasis, 50% were endovenous drug users (1990-2001). Presenting mean 77 CD4+ T cells/mm3, one was C2 and 11 were C3 (HIV classification, according to CDC) and 70% had positive serology for leishmaniasis. Presentation of TL in the skin and mucosa were diversified: single or multiple ulcers and polymorphic or disseminated lesions, including lesions in genital area in 4 cases. All were treated with anti-leishmanial drugs and 50% with HAART. 50% presented relapse and 50% died during follow up period, independently of use of HAART

Realizou-se um estudo descritivo conduzido no Hospital de Clínicas de Porto Alegre, no período de outubro de 2001 a outubro de 2002, com pacientes HIV positivos e anêmicos. Objetivo: avaliar a associação entre anemia e o perfil nutricional em uma amostra de pacientes HIV+ . Métodos: Foram incluídos 34 pacientes maiores de 18 anos, sendo todos pacientes diagnosticados com anemia. Foram analisados exames laboratoriais, avaliação da ingestão alimentar (recordatório alimentar de 24h), freqüência alimentar e coleta dos parâmetros antropométricos dos pacientes. Resultados: O recordatório alimentar de 24 horas demonstrou a deficiência na ingestão de folato pela maioria dos pacientes; enquanto que vitamina B12 e ferro estiveram de acordo com as RDA’s. Conclusão: A causa da anemia nestes pacientes talvez não tenha sido em função desta deficiente ingestão de folato, ainda mais por se tratar de um estudo descritivo. Ressalta-se a importância do profissional para o acompanhamento nutricional destes pacientes, para a promoção de um adequado estado nutricional e qualidade de vida. / Was develop a descritive study conducted in the Porto Alegre Clinics’ Hospital, from october 2001 to October 2002, with positive HIV and anemics patients. Objectives: Evaluate the association between anemia and nutritional status in positive HIV patients. Methodology: Were included 34 patients under 18 years old, all diagnosed with anemia. Laboratorial exams, evaluation of food intake (24h register), questionary of food intake frequence and anthropometrics data were collected. Results: The 24h register food intake showed the deficiency in folate intake by most of patients ,while vitamine B12 and iron intake were accorded RDA’s. Conclusions: The etiology of anemia in these patients maybe wasn´t cause by this folate deficiency, also because this was a describe study. The presence of a professional appears to be important for the nutritional treatment of these patients, to develop a health nutrional status and quality of life.

Thesis (M.S.W.)--McGill University, 1998. / Includes bibliographical references (leaves 117-127).

Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1574. Adviser: Lu-Yu Hwang. Includes bibliographical references.

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