Orientador: César Apareciddo Nunes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação / Made available in DSpace on 2018-08-22T03:49:59Z (GMT). No. of bitstreams: 1 Fachini_MicheleAlexandra_M.pdf: 4919853 bytes, checksum: b1c590a7102d284dff5e17797a5c8c30 (MD5) Previous issue date: 2013 / Resumo: O estudo e as reflexões que empregamos para compreender a sexualidade de crianças e adolescentes que convivem com vírus HIV (Vírus da Imunodeficiência Adquirida) causador da doença Aids (Síndrome da Imunodeficiência Adquirida). Para isso delineamos as políticas de inclusão nos Campos da Saúde e da Educação e sua abrangência para os que convivem com o vírus HIV/Aids, questionamos as matrizes históricas e filosóficas de sustentação. Procuramos nos manuais, referenciais de apoio didático produzidos pelo Ministério da Saúde, na miúda produção acadêmica entre dissertações e teses na área da saúde, no documento 'Orientação Sexual', volume 10 dos Parâmetros Curriculares Nacionais (1997), e em livros paradidáticos conferidos pelo Ministério da Educação e Cultura. Para realizar essa tarefa nos apropriaremos como base teórica dos conceitos imbricados na produção do conhecimento sobre sexualidade no Grupo de Pesquisa Paideia (UNICAMP). Assim, buscamos na produção do autor César Nunes a fundamentação da Educação Sexual Emancipatória para interpretar tal problematização, sob a concepção dialética da sexualidade. Reconhecemos nessa investigação crítica os sentidos e significados para a sexualidade de crianças e adolescentes que convivem com o vírus HIV inspirada numa resolução fundamentalmente pessoal e subjetiva. / Abstract: The study and reflection that we use to understand the sexuality of children and adolescents living with HIV (Human Immunodeficiency Virus) that causes the disease AIDS (Acquired Immunodeficiency Syndrome). For this inclusion policies outlined in the Fields of Health and Education and its scope for those living with HIV / AIDS: (we also question the historical and philosophical matrix). We searched textbooks, teaching aids benchmarks produced by the Ministry of Health, the little girl production of academic dissertations and theses in health, in the document 'Sexual Orientation', volume 10 of the National Curriculum (1997), books and textbooks conferred by Ministry of Education and Culture. To accomplish this task, rely on the theoretical concepts of the production of knowledge about sexuality in the Research Group Paideia (UNICAMP). Thus, we sought the production of the author César Nunes the grounds of Sex Education Emancipation for interpreting such questioning under the dialectical conception of sexuality. We recognize that critical research the senses and meanings for sexuality of children and adolescents living with HIV in a resolution inspired fundamentally personal and subjective. / Mestrado / Filosofia e História da Educação / Mestra em Educação

HIV and AIDS are casting a dark shadow over the future of many developing countries in the world. Since the first diagnosis of AIDS cases, South Africa has become one of the countries most infected with the HIV and AIDS pandemic, with about five million people living with HIV and AIDS. HIV prevalence is high in the age group 15 to 49 years, attacking people in the most productive years of their lives, Africans are the most significant racial group, affected and the Eastern Cape rates sixth in terms of HIV prevalence in the country. Demographically, HIV and AIDS affects the structure of the population, including learner and educator populations, as HIV and AIDS impact on the demand and supply of education. Schools are negatively and diversely impacted by the new challenges of the pandemic, preventing schools from achieving their goals. South Africa is struggling with a shortage of educators in the school system, especially the key areas of science and mathematics. The number of potential learners is expected to decline as AIDS orphans and other vulnerable children drop out of school, relocate, do not enrol, or are forced to withdraw from the school system. These factors lead to a poor morale and unproductivity among educators and learners, causing management problems in education for school principals and a decline in the quality and efficiency of education. While there is still no known cure for HIV and AIDS, the only solution in curbing the spread of the pandemic is through education and changing the social behaviours and mindset of people. However, HIV and AIDS prevention interventions have clearly been ineffective, as infection rates are soaring. As HIV and AIDS infection rates escalates, a more urgent response by school principals is needed to address the unique demands of the pandemic and establish where HIV and AIDS interventions will be most successful. The current study had three major aims. The aims were to explore how school principals in the Eastern Cape perceive the HIV and AIDS pandemic; describe in detail how school principals in the Eastern Cape respond to the HIV and AIDS pandemic; and to formulate recommendations based on the findings of the research that will assist school principals in effectively managing the pandemic at school level. The sample consisted of twelve school principals from different schools in the urban areas of Nelson Mandela Bay and the rural Keiskammahoek area. A qualitative method was selected to capture the unique experiences of school principals. In-depth, unstructured interviews were conducted to gather information. Thereafter, the interviews were transcribed verbatim, analysed and interpreted to gain a deeper understanding of the research phenomenon. The findings of the study revealed that the majority of school principals had limited knowledge only of the HIV and AIDS pandemic, and perceived the pandemic in a non-constructive manner, as an imminent future problem. In fact, many school principals were ambiguous, contradictory and discriminatory in their discussion in their responses to the pandemic, first denying the presence of AIDS cases in their schools, then shifting the blame for the spread of HIV and AIDS in their schools to others. These school principals were clearly unaware that they were being discriminatory and secretive about the pandemic through denial and blaming others and that their attitudes were fuelling stigmatization and discrimination. The school principals acknowledged that much more still needed to be done in terms of management and leadership to effectively mitigate the effects of the pandemic in their schools. While school principals did their best in dealing with HIV and AIDS related problems at their schools, they clearly lacked the necessary skills, training and knowledge to devise long-term strategies to deal effectively and pro-actively with the problems related to the pandemic. Therefore a more transformational leadership and management approach is required by school principals in dealing with the pandemic in their schools, in order to render them effective leaders.

Le virus de l’immunodéficience humaine de type 1 (VIH-1) est l’agent étiologique du SIDA. Il pénètre dans les cellules cibles par fusion membranaire médiée par le complexe enveloppe (Env) exprimé à la surface du virion. Le complexe est constitué d’une sous-unité de surface (gp120), et d’une sous-unité transmembranaire (gp41), exprimées sous forme trimérique. La liaison de gp120 au récepteur CD4 induit un premier changement de conformation qui expose la boucle hypervariable V3. Cette dernière lie un corécepteur, CCR5 et/ou CXCR4, induisant de nouveaux changements conformationnels au niveau de gp41 qui aboutissent à l’insertion du peptide de fusion, situé à l’extrémité N-terminale de gp41, dans la membrane de la cellule cible. Suite à la liaison du corécepteur, la région « heptad repeat 1 » (HR1) de gp41 interagit avec la région « heptad repeat 2 » (HR2) du même monomère pour former une structure coiled-coil hexamérique. Ce repliement permet le rapprochement des membranes virale et cellulaire, conduisant à la fusion des membranes.<p>Le processus d’entrée constitue une cible de choix pour inhiber la propagation du virus et à l’heure actuelle, il existe deux classes d’inhibiteurs d’entrée utilisés en clinique :les inhibiteurs de fusion et les inhibiteurs du CCR5. Le but de ce travail de thèse est l’étude des déterminants de l’enveloppe virale impliqués dans l’échappement du VIH-1 au traitement avec des inhibiteurs de fusion et de l’entrée.<p>La première partie de ce travail de thèse a étudiée l’effet modulateur des déterminants de l’enveloppe virale sur le niveau de résistance et de l’infectivité des virus primaires porteurs de mutations de résistance à l’enfuvirtide dans HR1 et de mutations compensatrices dans HR2. Nous avons sélectionné 5 patients ayant reçu un traitement à long terme incluant de l’enfuvirtide. Les enveloppes de virus ont été clonées à partir d’échantillons plasmatiques séquentiels, prélevés avant le début du traitement et pendant le suivi du traitement à l’enfuvirtide. Les séquences ont été caractérisées génotypiquement et phénotypiquement à l’aide de tests viraux recombinants mis au point à cet effet, et ciblant soit la région HR1-HR2, soit l’enveloppe entière. Pour les échantillons pré-thérapeutiques, les virus recombinants Env exprimaient des taux de sensibilité à l’enfuvirtide plus variables que les virus recombinants HR1-HR2, et une sensibilité à l’enfuvirtide significativement moindre que les virus HR1-HR2, indiquant que le contexte génétique de l’enveloppe affecte directement le niveau de susceptibilité du virus envers l’enfuvirtide. Après échec virologique, l’analyse phénotypique comparative des virus résistants suggère que les régions HR1-HR2 contiennent, à elles seules, les déterminants qui régissent la résistance. Le seul facteur associé à une modulation significative de la résistance est le tropisme. L’infectivité des virus Env a augmenté au cours du temps, alors que pour les virus HR1-HR2, l’infectivité est restée stable. Nos résultats suggèrent donc que le niveau de résistance confère un avantage sélectif initial sous pression sélective par l’enfuvirtide, alors que, une fois le niveau de résistance optimisé, l’infectivité des virus résistants est le facteur qui détermine la sélection des virus sous pression de sélection prolongée.<p>La deuxième partie de notre travail a été consacrée au rôle des virus dans des sites sanctuaires tels que le système nerveux central, et au rôle de séquences archivées dans les PBMCs dans l’échappement aux inhibiteurs d’entrée.<p>Dans une première étude clinique, nous avons illustré le rôle direct de la suppression incomplète du virus dans le système nerveux central dans l’acquisition de mutations de résistance à l’enfuvirtide et dans l’échec virologique. Le génotypage des virus plasmatiques et des virus isolés du liquide céphalo-rachidien d’un patient en échec de traitement a montré que la mutation de résistance à l’enfuvirtide était apparue dans le liquide céphalo-rachidien avant qu’elle ne devienne détectable dans le plasma, au moment de l’échec virologique. Le virus plasmatique résistant était phylogénétiquement proche du virus résistant isolé à partir du LCR, suggérant que la mutation de résistance a émergé dans ce compartiment. Ainsi, la pénétration incomplète des antirétroviraux dans le système nerveux central a abouti à la sélection de virus résistants, qui ont ensuite traversé la barrière céphalo-rachidienne pour atteindre la circulation périphérique.<p>Dans une seconde étude clinique, la caractérisation génotypique et phénotypique du tropisme de virus plasmatiques et cellulaires de deux patients en échec de traitement par du maraviroc ainsi que l’analyse phylogénétique rétrospective nous a permis de mettre en évidence l’importance de la recombinaison génétique dans la diversification des populations virales et son importance dans l’échec thérapeutique au maraviroc par l’émergence de virus X4. Par cette étude nous avons également pu souligner l’importance de l’administration iatrogène d’interleukine-2 sur la distribution et la modulation des populations X4 et R5 au niveau des compartiments cellulaires et plasmatiques et son importance dans l’échec thérapeutique au maraviroc.<p>En conclusions, nos résultats ont permis de mettre en évidence le pouvoir adaptatif du VIH-1 dans l’échappement au traitement aux inhibiteurs de l’entrée ainsi que le rôle majeur des sites sanctuaires et des virus archivés.<p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Master of Public Health - MPH / Increasing HIV infection rates affect government employees as much as workers in other places. While government has responded to the evolving crisis with a number of policy documents, little is known about the implementation of such policies in government departments. This study assessed the HIV/AIDS policy in the Department of Labour and identified weakness in the implementation. The results of the study may be used by the Dept. of Labour to improve its implementation if necessary. / South Africa

Magister Artium - MA / This study investigated the societal perception of refugee men as being a risk group, being polluted and the consequent risk of HIV infection they might face. It also determined the factors that could expose them to the risk of HIV infection while living in exile in South Africa. / South Africa

This study has focused on the synthesis of truncated analogues of the hydroxyethylene dipeptide isosteres, such as Ritonavir®, currently in clinical use as HIV-1 protease inhibitors. The reactions of pyridine-2- and quinoline-2-carbaldehydes with methyl acrylate, in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) or 3- hydroxyquinuclidine (3-HQ) as nucleophilic catalysts, have afforded a series of Baylis- Hillman adducts, acetylation and cyclisation of which have provided access to a series of indolizine-2-carboxylate esters. The carboxylic acids, obtained by base-catalyzed hydrolysis of these esters, have been coupled with various protected (and unprotected) amino compounds using the peptide coupling agent, 1,1’-carbonyldiimidazole (CDI), to afford a series of indolizine-2-carboxamides as indolizine-based truncated Ritonavir® analogues in quantitative yield. Aza-Michael reactions of pyridine-3-carbaldehydederived Baylis-Hillman adducts with various amino compounds have provided access to a range of pyridine-based products as mixtures of diastereomeric aza-Michael products. The assignment of the relative stereochemistry of the aza-Michael products has been established using 1-D and 2-NOESY experiments and computer modelling techniques. Computer modelling studies have also been conducted on selected aza-Michael products using ACCELRYS Cerius2 software, followed by interactive docking into the HIV-1 protease receptor site, using AUTODOCK 4.0. The docking studies have revealed hydrogen-bonding interactions between the enzyme and the synthetic ligands. Saturation Transfer Difference (STD) NMR experiments have also indicated binding of some of the aza-Michael products to the HIV-1 protease subtype C enzyme, thus indicating their binding and possible inhibitory potential.

The project has focused on the preparation of several series of compounds designed as potential HIV-1 integrase inhibitors. Various 2-nitrobenzaldehydes have been reacted with two activated alkenes, methyl vinyl ketone (MVK) and methyl acrylate, under Baylis-Hillman conditions to afford α-methylene-β-hydroxylalkyl derivatives in moderate to excellent yields. The reactions were conducted using the tertiary amine catalysts, 1,4-diazabicyclo[2.2.2]octane(DABCO) or 3-hydroxyquinuclidine (3-HQ) with chloroform as solvent, and yields were optimised by varying the catalyst, reagent concentrations and the reaction time. Reductive cyclization of the Baylis-Hillman adducts via catalytic hydrogenation, using 10% palladiumon-carbon catalyst in ethanol, afforded quinoline and quinoline N-oxide derivatives. In some cases “acyclic” reduction products were also isolated. Reaction of the Baylis-Hillman MVK adducts with HCl, has resulted in effective nucleophilic (SN’) displacement of the hydroxyl group to afford allylic chloride derivatives. Direct substitution of these chloro derivatives by secondary or primary amines, followed by catalytic hydrogenation gave quinoline derivatives containing a 3-aminomethyl substituent. The Baylis-Hillman ester adducts obtained from reaction with methyl acrylate were treated directly with various amines to give diastereomeric conjugate addition products. Reactions with piperazine gave N,N’-disubstituted piperazine products. The piperidine derivatives have been dehydrated to give cinnamate esters in moderate yields. The products, which have all been satisfactorily characterised by elemental (HRMS) and spectroscopic (1- and 2-D NMR) analysis, constitute a “library” of compounds for in silico and in vitro studies as potential HIV integrase inhibitors.

This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex coumarin-AZT and cinnamate ester-AZT conjugates have been prepared, in high yields, by exploiting the click reaction between appropriate Baylis-Hillman derived precursors and azidothymidine (AZT), all of which have been fully characterised using spectroscopic techniques. These conjugates, designed as potential dual-action HIV-1 inhibitors, were tested against the appropriate HIV-1 enzymes, i.e. HIV-1 reverse transcriptase and protease or HIV-1 reverse transcriptase and integrase. A number of the ligands have exhibited % inhibition levels and IC50 values comparable to drugs in clinical use, permitting their identification as lead compounds for the development of novel dual-action inhibitors. In silico docking of selected ligands into the active sites of the respective enzymes has provided useful insight into binding conformations and potential hydrogen-bonding interactions with active-site amino acid residues. A series of furocoumarin carboxamide derivatives have been synthesised in four steps starting from resorcinol and these compounds have also been tested for HIV-1 integrase inhibition activity. The structures of unexpected products isolated from Aza-Baylis-Hillman reactions of N-tosylaldimines have been elucidated by spectroscopic analysis, and confirmed by single crystal X-ray analysis. A mechanism for what appears to be an unprecedented transformation has been proposed. Microwave-assisted SeO₂ oxidation of Baylis-Hillman-derived 3-methylcoumarins has provided convenient and efficient access to coumarin-3-carbaldehydes, and a pilot study has revealed the potential of these coumarin-3-carbaldehydes as scaffolds for the construction of tricyclic compounds. The HCl-catalysed reaction of tert-butyl acrylate derived Baylis-Hillman adducts has been shown to afford 3-(chloromethyl)coumarins and α-(chloromethyl)cinnamic acids, the Zstereochemistry of the latter being established by X-ray crystallography. ¹H NMR-based experimental kinetic and DFT-level theoretical studies have been undertaken to establish the reaction sequence and other mechanistic details. Base-catalysed cyclisation on the other hand, has been shown to afford 2H-chromene rather than coumarin derivatives.

Despite the current interventions to avert contagions and AIDS-related deaths, sub-Saharan Africa is still the region most severely affected by the HIV/AIDS pandemic, where clade C is the dominant circulating HIV-1 strain. The pol-encoded HIV-1 protease enzyme has been extensively exploited as a drug target. Protease inhibitors have been engineered within the framework of clade B, the commonest in America, Europe and Australia. Recent studies have attested the existence of sequence and catalytic disparities between clades B and C proteases that could upset drug susceptibilities. Emergence of drug-resistant associated mutations and combinatorial explosions due to recombination thwarts the attempt to stabilize the current highly active antiretroviral therapy (HAART) baseline. The project aimed at identifying the structural and molecular mechanisms hired by mutants to affect the efficacies of both FDA approved and Rhodes University (RU)-synthesized inhibitors, in order to define how current and or future drugs ought to be modified or synthesized with the intent of combating drug resistance. The rationale involved the generation of homology models of the HIV-1 sequences from the South African infants failing treatment with two protease inhibitors: lopinavir and ritonavir (as monitored by alterations in surrogate markers: CD4 cell count decline and viral load upsurge). Consistent with previous studies, we established nine polymorphisms: 12S, 15V, 19I, 36I, 41K, 63P, 69K, 89M, and 93L, linked to subtype C wild-type; some of which are associated with protease treatment in clade B. Even though we predicted two occurrence patterns of M46I, I54V and V82A mutations as V82A→I54V→M46I and I54V→V82A→M46V, other possibilities might exist. Mutations either caused a protracted or contracted active site cleft, which enforced differential drug responses. The in silico docking indicated susceptibility discordances between clades B and C in certain polymorphisms and non-polymorphisms. The RU-synthesized ligands displayed varied efficacies that were below those of the FDA approved protease inhibitors. The flaps underwent a wide range of structural motions to accommodate and stabilize the ligands. Computational analyses unravelled the need for these potential drugs to be restructured by (de novo) drug engineers to improve their binding fits, affinities, energies and interactions with multiple key protease residues in order to target resilient HIV-1 assemblages. Accumulating evidences on contrasting drug-choice interpretations from the Stanford HIVdb should act as an impetus for the customization of a HIVdb for the sub-Saharan subcontinent.

Pharmacological interventions to treat Human Immunodeficiency Virus (HIV) with antiretrovirals (ARVs), have dramatically improved the survival rates of HIV positive children maturing into adulthood. However, HIV-associated neurocognitive decline still persists in the era of ARVs. Within the framework of brain plasticity, a number of researchers have begun to assess the feasibility of cognitive rehabilitation therapy as a complement to ARVs to reverse neurocognitive decline as a result of HIV (e.g., Becker et al., 2012). Only one study has been conducted in South Africa, by Zondo & Mulder (2014), assessing the efficacy of cognitive rehabilitation in a paediatric sample. The current research builds on the above mentioned study by implementing an experimental approach to examine the effect of cognitive rehabilitation in a sample of both HIV positive and HIV negative children. Five HIV positive and six HIV negative children were assigned to either an experimental or control group. The experimental group underwent two months of cognitive rehabilitation therapy remediating sustained attention, whereas the control group took part in placebo activities. Sustained attention measures were taken before and after the intervention training sessions, using a sustained attention subtest from the Test of Everyday Attention for Children (TEA-CH). A Mann Whitney U Test revealed that the experimental group (Mdn=38.50) did not differ significantly from the control group (Mdn = 37.00) after the cognitive rehabilitation intervention, U=12.00, z= -.55, p= .66, r= -.17. But a Wilcoxon Signed Rank Test found that there was a significant improvement from pretest scores (Mdn=31.00) to posttest scores (Mdn=38.00) following the rehabilitation for HIV positive participants in the sample, T=15.00, z = -2.02, p= .04, r= -.90. This raises the possibility that cognitive rehabilitation could be used as a low cost intervention in underdeveloped contexts