>Magister Scientiae - MSc / Background and Aims Human Immunodeficiency Virus (HIV) type 1 group M subtype C (HIV-1C) accounts for nearly half of global HIV-1 infections, with South Africa (SA) being one of the countries with the highest infection burden. In recent years, SA has made great strides in tackling its HIV epidemic, resulting in the country being recognized globally as the one sub-Saharan country with the largest combination antiretroviral therapy (cART) programme. Regardless of the potency of cART, the efficacy of the treatment is limited and hampered by the emergence of drug resistance. The majority of research on HIV-1 infections, effect of antiretroviral (ARV) drugs and understanding resistance to ARV drugs has been extensively conducted, but mainly on HIV-1 subtype B (HIV-1B), with less information known about HIV-1C. HIV-1’s viral Integrase (IN) enzyme has become a viable target for highly specific cART, due to its importance in the infection and replication cycle of the virus. The lack of a complete HIV-1C IN protein structure has negatively impacted the progress on structural studies of nucleoprotein reaction intermediates. The mechanism of HIV-1 viral DNA’s integration has been studied extensively at biochemical and cellular levels, but not at a molecular level. This study aims to use in silico methods that involve molecular modeling and molecular dynamic (MD) simulations to prioritize mutations that could affect HIV-1C IN binding to DNA and the IN strand-transfer inhibitor (INSTI) dolutegravir (DTG). The purpose is to help tailor more effective personalized treatment options for patients living with HIV in SA. This study will in part use patient derived sequence data to identify mutations and model them into the protein structure to understand their impact on the HIV-1C IN protein structure folding and dynamics. Methods Our sample cohort consisted of 11 sample sequences derived from SA HIV-1 treatmentexperienced patients who were being treated with the INSTI raltegravir (RAL). The sequences were submitted to the Stanford HIV resistance database (HIVdb) to screen for any new/novel variants resulting from possible RAL failure. Some of these new variants were analyzed to analyse their effect, if any, on the binding of DTG to the HIV-1C IN protein. Additionally, an HIV-1C IN consensus sequence constructed from SA’s HIV-1 infected population was used to model a complete three-dimensional wild type (WT) HIV-1C IN homology model. All samples were sequenced by our collaborators at the Division of Medical Virology, Stellenbosch University together with the National Health Laboratory Services (NHLS), SA. The HIV-1CZA WT-IN protein enzyme was predicted using SWISS-MODEL, and the quality of the resulting model validated. Various analyses were conducted in order to study and assess the effect of the selected new variants on the protein structure and binding of DTG to the IN protein. The mutation Cutoff Scanning Matrix (mCSM) program was used to predict protein stability after mutation, while PyMol helped to study any changes in polar contact activity before and after mutation. PyMol was also used to generate four mutant HIV-1C IN complex structures and these structures together with the WT IN were subjected to production MD simulations for 150 nanoseconds (ns). Trajectory analyses of the MD simulations were also conducted and reported. Results A total of 21 new variants were detected in our sample cohort, from which only six were chosen for further analyses within the study. A homology model of HIV-1C IN was successfully constructed and validated. The structural quality assessment indicated high reliability of the HIV-1C IN tetrameric structure, with more than 90.0% confidence in modelled regions. Of the six selected variants, only one (S119P) was calculated to be slightly stabilizing to the protein structure, with the other five found to be destabilizing to the IN protein structure. Variant S119P showed a loss in polar contacts that could destabilize the protein structure, while variant Y143R, resulted in the gain of polar contacts which could reduce flexibility of the 140’s region affecting drug binding. Similarly, mutant systems P3 (S119P, Y143R) and P4 (V150A, M154I) showed reduced hydrogen bond formation and the weakest non-bonded pairwise interaction energy. These two systems, P3 and P4, also showed significantly reduced to none polar contacts between DTG, magnesium (MG) ions and the IN protein, compared to the WT IN and P2 mutant IN systems. Interestingly, the WT structure and systems P1 (I113V) and P2 (L63I, V75M, Y143R) showed the highest non-bonded interaction energy, compared to systems P3 and P4. This was further supported by the polar interaction analyses of simulation clusters from the WT IN and mutant IN system P2 (L63I, V75M, Y143R), which were the only protein structures that formed polar contacts with DTG, MG ions and DDE motif residues, while P1 only made contacts with DNA and IN residues. Conclusion Findings from this study leads to a conclusion that double mutants (S119P, Y143R) and (V150A, M154I) may result in a reduction in the efficacy of DTG, especially when in combination. Furthermore, variants identified in systems P1 and P2 may still allow for effective DTG binding to IN and outcompete viral DNA for host DNA to prevent strand transfer. To the best of our knowledge, this is the first study that uses the consensus WT HIV1C IN sequence to build an accurate 3D homology model to understand the effect of less frequently detected/reported variants on DTG binding in a South African context. https://etd.

The human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) that subsequently develops remain major health concerns even after three decades since the first cases were reported. Successful therapeutic measures to address HIV/AIDS consist mostly of combinations of drugs targeting viral enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) as well as entry steps of the viral life cycle. The remarkable benefits (e.g. improved quality of life) derived from the use of these agents are unfortunately limited by toxicity to the host and the development of drug resistant viral strains. Drug resistance limits the repertoire of drug combinations available. Unfortunately, because latent forms of the virus exists, therapy has to be life-long and with new infections occurring every day, resistant strains tend to spread. To circumvent these problems, new drugs that inhibit resistant strains or work against new viral targets have to be developed. The history of gold compounds as potential inhibitors of HIV prompted this study in which twenty seven compounds consisting of gold(I), gold(III) and precursors from five classes were tested for drug-likeness, anti-HIV and immunomodulatory effects using wet lab and in silico methodologies. Cytotoxicity determination was done using viability dyes and flow cytometry. Cell proliferation profiles were monitored using the carboxyflourescein succinimidyl ester dye dilution technology and a real time cell analyser for confirming viability dye findings. The compounds’ effects on viral enzymes was determined using direct enzyme assays and in silico molecular modelling techniques. H and P nuclear magnetic resonance spectroscopy studies for determining stability revealed that the backbone chemical shifts of the compounds were relatively unchanged after one week (-20 and 37 ºC) when dissolved in dimethylsulfoxide. Eight of the gold compounds had drug-like properties comparable to clinically available drugs when in silico predictions were performed. The 50% cytotoxic dose of the compounds in human cells was between 1 and 20 μM (clinically relevant concentrations for gold compounds). Three gold(I) compounds inhibited viral infectivity at non-toxic concentrations and two gold(III) compounds did so at cytostatic (anti-proliferative mechanism that is also antiviral) concentrations. In the immunomodulatory assay, cytokine levels were altered by five compounds with one gold(I) and a gold(III) compound significantly reducing the frequency of CD4+ cells (an anti-viral function) from HIV+ donors (p= 0.005 and 0.027 respectively) when multi-parametric flow cytometry was performed. Inhibition of RT activity was predicted in in silico studies to be through interactions with the ribonuclease (RNase) H site although with poor stereochemical orientation while favourable binding predictions with the IN cofactor binding site were observed for some gold(III) complexes. Compounds predicted to interact with the RNase H site of RT and the IN cofactor site require structural modification to improve drug-likeness and binding affinity. The drug-like compound(s) which inhibited viral infectivity and lowered CD4+ cell frequency have potential for incorporation into virostatic cocktails (combination of cytostatic and directly anti-viral agent). Cytostatic agents are known to be less prone to drug resistance and because they lower CD4+ cell frequency, such compounds can potentially limit HIV immune activation. / Thesis (PhD)--University of Pretoria, 2011. / Biochemistry / unrestricted

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic has surpassed forty years with many medical advancements in prevention and treatment. Often believed to be at negligible or low risk by society at large, sexual minority women have remained understudied regarding their risk of HIV and other sexually transmitted infections (STIs), leaving their sexual health inadequately understood and supported in healthcare and social services. The sexual health of young South Asian sexual minority women, who are multiply minoritized due to their intersecting identities, has been entirely overlooked. This qualitative study aimed to understand the knowledge, attitudes, and practices of young South Asian sexual minority women as it pertains to their HIV/STI risk. Barriers and facilitators to accessing community-based sexual health supports and services were also investigated. A community-engaged approach was taken to develop this study in partnership with the Alliance for South Asian AIDS Prevention to investigate the HIV/STI risk context and sexual health needs of this group residing in the Greater Toronto Area. A maximum variation sampling strategy was used to recruit six young South Asian sexual minority women and semi-structured in-depth interviews were conducted to collect narrative data. Narrative analysis of the data found socio-cultural and structural influences which guide the HIV/STI risk context for this group. The participants illuminated an inadequate understanding of sexual health when engaging in sex with women, an overall low HIV/STI risk perception, barriers to adequate sexual healthcare and health promotion resources, and multiple minority stressors which impacted their access to safe sex. These findings have major implications for school-based sexual health education, medical training for healthcare practitioners, and sexual health support and services provided by community-based sexual health organizations in the Greater Toronto Area. / Thesis / Master of Public Health (MPH)

Magister Pharmaceuticae - MPharm / Background: Tenofovir disoproxil fumarate (TDF) and Zidovudine (AZT) are both nucleotide and nucleoside analogue reverse transcriptase inhibitors (NtRTIs and NRTIs), respectively. They are used for the management and prevention of the Human Immunodeficiency Virus (HIV) infection. These drugs are faced with oral delivery challenges such as low intestinal permeability and extensive first pass liver metabolism for TDF and AZT, respectively. Their use may also be limited by dose-dependent adverse effects, which may result in treatment failure when patients become non-compliant and non-adherent to their prescribed antiretroviral (ARV) regimen. Non-compliance and non-adherence to ARV regimen may lead to drug resistance and a need for change in regimen, which can be very expensive, not only financially but in terms of morbidity and mortality. To solve such issues, a new drug can be formulated, or an existing drug can be modified. The development and formulation of a new drug is time consuming and expensive, especially with no available data and a high probability of failure. Modifying existing drugs is a cheaper, less time-consuming option with lower probability of failure. Such modification can be achieved via non-covalent interactions using various methods such as preparation of nano-particulates with polymeric micelles (a non-covalent interaction). Polymeric micelles offer a variety of polymers to choose from for drug modification purposes. Purpose: The aim of this study was to formulate polymeric nanoparticles of TDF and AZT using different ratios of poly-lactic-co-glycolic acid (PLGA), characterize the formulated nanoparticles (using the following analyses: particle size, zeta potential, encapsulation efficiency, hot stage microscopy, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy), analyze for stability during storage (2-8˚C) and determine the release rate of the active pharmaceutical ingredients in the formulated nanoparticles. Methods: Nanoparticles were prepared using a modified version of the double emulsion (water-in-oil-in-water) solvent evaporation and diffusion method. Two ratios of PLGA (50:50 and 85:15) were used to prepare four formulations (two each of TDF and AZT). Thereafter, the physicochemical and pharmaceutical properties of the formulations were assessed by characterizing the nanoparticles for particle size, zeta potential, polydispersity index, percentage yield, release profile and particle morphology, using the suggested analytical techniques. Results: For TDF-PLGA 85:15, TDF-PLGA 50:50, AZT-PLGA 85:15 and AZT-PLGA 50:50, nanoparticles of 160.4±1.7 nm,154.3±3.1 nm,127.0±2.32 nm and 153.2±4.3 nm, respectively, were recovered after washing. The polydispersity index (PDI) values were ≤0.418±0.004 after washing, indicating that the formulations were monodispersed. The zeta potential of the particles was -5.72±1 mV, -19.1 mV, -12.2±0.6 mV and -15.3±0.5 mV for TDF-PLGA 85:15, TDF-PLGA 50:50, AZT-PLGA 85:15 and AZT-PLGA 50:50 respectively after washing. The highest percentage yield was calculated to be 79.14% and the highest encapsulation efficiency obtained was 73.82% for AZT-PLGA 50:50, while the particle morphology showed spherical nanoparticles with signs of coalescence and aggregation for all formulated nanoparticles. The release profiles were biphasic; that is, an initial burst which indicated the presence of surface API followed by sustained release. Comparing the release profiles of AZT and TDF at pH 1.2 and 7.4, it was indicative that more AZT was released at pH 1.2 while more TDF was released at pH 7.4. On computing the release data further into various mathematical models, the Weibull model was found to be the best fit. The loaded nanoparticles showed an increase in stability after washing; however, they showed signs of gradual decrease in stability after 10 days of storage at 2-8°C. Conclusions: Relatively small, spherical and smooth nanoparticles were formulated. The nanoparticle release profile was indicative of sustained release; however, there was no conclusive indication that 48 hours duration was sufficient to release all encapsulated drug. Further studies with an increased API or polymer ratio in the formulation needs to be performed to determine if the encapsulation efficiency can be improved and in-vivo studies are required for a better understanding of the API release from formulations as well as its absorption in the body.

O panorama epidemiológico da AIDS indica a expansão da epidemia entre mulheres e conseqüentemente a infecção de crianças através da transmissão vertical. As crianças acometidas pela AIDS podem apresentar diversos sintomas e sinais próprios da doença, entre eles, atraso no desenvolvimento neuropsicomotor. No entanto, crianças filhas de mães soropositivas mesmo quando não infectadas, podem sofrer as conseqüências da doença em sua família. Os objetivos deste estudo foram: comparar o desenvolvimento neuropsicomotor de crianças não infectadas filhas de mães soropositivas para o HIV com crianças não expostas ao vírus; identificar fatores para atraso no desenvolvimento destas crianças e refletir sobre a necessidade de intervenção pela terapia ocupacional. Foram comparados dois grupos, com 45 crianças em cada um deles, nas idades de 3, 8 e 18 meses. Em relação ao desenvolvimento neuropsicomotor não foram encontradas diferenças entre o grupo de crianças filhas de mães soropositivas para o HIV e crianças não expostas ao vírus nas idades em conjunto, porém foi encontrada diferença significativa entre eles na idade de 3 meses. Também foram encontradas diferenças significativas entre os grupos quando comparados quanto à renda familiar, ao peso da criança ao nascimento e ao hábito materno da utilização de drogas ilícitas. Contudo, aos 3 meses de idade, apenas o hábito materno da utilização de drogas ilícitas influenciou negativamente o desenvolvimento neuropsicomotor das crianças. Os resultados permitiram discutir o papel do terapeuta ocupacional junto a esta população e sugere-se que novos estudos envolvendo o tema poderão colaborar com a confirmação dos dados obtidos, bem como dar continuidade às reflexões sobre a atuação deste profissional. / The Aids epidemiological background indicates the spread of epidemic among women and consequentially the infection of children through vertical transmission. The HIV infected children can show several peculiar symptoms and signs of the disease, such as the delay in the neuropsychomotor development. Nevertheless, children born to HIV-infected women even when uninfected, might suffer the disease consequences in their family. The objectives of this study are: to compare neuropsychomotor development of uninfected children born to HIV-infected women to children not exposed to the virus; to identify factors that influence the delay of children development and discuss the need for intervention by Occupational Therapy. Comparing the group of children born to HIV-infected women to children not exposed (in each group were included 45 children), in the three studied ages (3, 8 e 18 months), no differences were found related to the neuropsychomotor development, but in the age of 3 months a significant difference was observed. Significant differences were also found among the groups when familiar income, at birth weight of children and maternal habits of illicit drug use were analyzed. However, in the age of 3 months, only the maternal habit of illicit drug use had negative effects in the neuropsychomotor development. According to the results, it’s possible to discuss the occupational therapist practice with this population and to suggest the need of new studies related to this subject that can contribute to the confirmation of the data and also continue the discussing about this professional actuation.

Abstract Background: Deficiency of Von Willebrand Factor Cleaving Protease (VWFCP) has been implicated as the cause of Thrombotic Thrombocytopenic Purpura (TTP). TTP is a lifethreatening disease characterised by microangiopathic thrombosis due to accumulation of Ultralarge Von Willebrand Factor (ULVWF) multimers. The clinical features of TTP include microangiopathic haemolysis and thrombocytopenia. TTP is being seen with increased frequency in the context of HIV. However, in the context of HIV infection, cytopenias are often multifactorial in nature and levels of VWFCP in HIV-related thrombocytopenia have not specifically been assessed. This study assessed VWFCP activity in the setting of patients with HIV and thrombocytopenia in the absence of TTP, in order to determine the utility of a VWFCP assay in the diagnosis of HIV-related TTP. Acquired VWFCP deficiency is generally assumed to be due to the presence of autoantibody inhibitors to the enzyme, but limited data are available regarding VWFCP activity in HIV positive TTP patients. There is also currently no assay available for measuring VWFCP activity in our laboratory. Aim of Study: To establish a practical assay for VWFCP activity for routine use in our laboratory. The rapid collagen binding assay, based on the ELISA method of Rick, et al., 2002, was chosen. This was initially used to measure VWFCP activity in patients with HIV with and without thrombocytopenia (of any cause except TTP), in order to ascertain whether assessment of VWFCP activity is likely to be of value in facilitating early diagnosis of HIV related TTP. The ELISA assay was performed to establish cut-off values for VWFCP in HIV negative controls and two HIV positive groups (HIV thrombocytopenia / low platelets and HIV normal platelets). Depending on the outcome of this, the assay could then be performed to assess VWFCP activity in HIV positive patients with TTP. Methods: The rapid collagen binding assay for VWFCP activity was established and optimised for routine use in our laboratory. The cut-off values for percentage Residual Collagen Binding Activity (RCBA) in both HIV negative and HIV positive groups were identified. The assay could then be used to assess VWFCP activity in 20 HIV positive patients with TTP at the time of presentation. In patients with reduced VWFCP activity, patient plasma was mixed with normal pool plasma in a 50:50 mix, to assess for the presence of inhibitors. Correlation of VWFCP activity, inhibitors and other laboratory and clinical parameters were performed. Results: The cut-off values for percentage RCBA in both HIV negative (<37.12%) and HIV positive (<51.51%) patients were established. The % RCBA for the HIV negative control group was statistically significantly different from the HIV positive group with normal platelets (p=0.0001) and from the HIV positive group with low platelets (p=0.0006). The cut-off value in the two HIV positive patient groups was higher than for HIV negative control patients, indicating mildly reduced VWFCP enzyme activity in HIV positive patients (regardless of the platelet count), in the absence of TTP. However, no significant difference in the cut-off value was noted between HIV positive patients with low platelet counts versus HIV positive patients with normal platelet counts (p=0.7783). The assay could therefore be used in HIV positive patients with TTP. VWFCP activity was assessed in twenty HIV positive patients with TTP. Two groups of HIV positive patients with TTP were identified based on VWFCP activity. Six patients (30%) had normal (one borderline) VWFCP activity (RCBA <51.51%), while the remaining 14 patients had severely reduced VWFCP levels (RCBA >90%). Of the patients with reduced VWFCP activity, only 5 patients had a detectable inhibitor, while an inhibitor was not detected in the remaining 8 patients. Conclusion: The rapid collagen binding ELISA assay is a cost effective semi-quantitative assay for the assessment of VWFCP activity. VWFCP activity in HIV positive patients appears to be slightly lower, however is not related to the platelet count. This suggests a slight baseline deficiency of VWFCP in the setting of HIV. The baseline VWFCP cut-off value in HIV allowed assessment of HIV positive patients with TTP. The results suggest heterogeneity of VWFCP activity in HIV-related TTP. A negative result (normal VWFCP activity) does not exclude TTP in patients with HIV-related TTP and other pathogenic factors may therefore be involved.

Made available in DSpace on 2014-12-17T14:46:53Z (GMT). No. of bitstreams: 1 JaquelineMBS_DISSERT.pdf: 1765859 bytes, checksum: 6d288bdaf8d4615845eb0265dedead22 (MD5) Previous issue date: 2011-12-13 / The counseling on HIV/Aids consists in a prevention strategy that contributes to increase the diagnosis of HIV and start earlier the treatment. The counseling has as pillars the emotional and educational support, risks evaluation that aim at the adoption of safe practices and the individual s responsibility for his own health. To accomplish these results, it is necessary that health workers understand counseling as a unique educational moment that stimulates the user s critical-reflection when it comes to his role as an active subject in this process. This study aimed to analyze the counseling on HIV/Aids conducted by the professionals of the Testing and Counseling Center (CTA), based on the educational perspective of Paulo Freire . This is a descriptive qualitative study with a critical reflexive design based on the principles of Action-Science. All the professionals acting as counselors in the Joao Pessoa, PB CTA, eight in total, took part in the study. Data were collected during the month of March, 2011, through non participative observation and semi-structured interviews with a critical-reflexive focus, analyzed according to the tenets of the critical-reflexive methodology, and discussed taking into consideration the Paulo Freire s pedagogy and pertinent literature. It was observed that most of the professionals expressed the work philosophy of CTA as the diagnosis and prevention of the disease, associated with the utilization and demonstration of condoms. However, upon observation of their counseling sessions, these ideas were not converted in actions. Educational themes were not covered and the condom wasn t offered at any time. The counseling actions focused on the provision of information and filling out the paper forms which are necessary for attendance. The sessions were conducted with brief dialogues and little opportunity for the users to expose or complement their thoughts and needs. The professionals mentioned as facilitating conditions for counseling, the team interaction and physical structure. The difficulties focused on the users low cognition, the large demand for attendance, aspects related to the service organization, and the counselors absences and delays. After reflecting about the actions observed in the counseling, the majority of professionals admitted the need to modify their practice in the incorporation of educational principles for the achievement of a broader prevention, and seemed to be willing to work in this perspective. In conclusion, although the counselors show ideas consistent with the purposes of CTA, these ideas are limited when it comes to the understanding of the meaning of prevention in HIV/Aids. Taking into consideration that they express a certain comprehension and act differently during the counseling, they demonstrate a lack of bond between the theories in use and the proposed ones, in accordance with the contribution of the action-science theory. The counseling, as an educative practice, doesn t materialize in the counseling itself and the orientation for reflection is not given during the attendance. These findings suggest the need to include the process of reflection in the execution of the actions of counseling, so that these practices are guided by reflexive practice, aiming at transforming the way of thinking and acting into a more educational perspective toward a more democratic and holistic assistance. / O aconselhamento em HIV/Aids consiste numa estrat?gia de preven??o pela qual ? poss?vel aumentar o diagn?stico do HIV e iniciar o mais precoce o tratamento. Os pilares que sustentam a estrat?gia s?o o apoio emocional e educativo, e a avalia??o de riscos, que visam ? ado??o de pr?ticas seguras e responsabilidade do sujeito como agente da sua sa?de. Para o alcance dos resultados, torna-se necess?rio que os profissionais de sa?de compreendam o aconselhamento como um momento educativo ?mpar, por estimular a reflex?o cr?tica do usu?rio no tocante ao seu papel como sujeito ativo nesse processo. Este estudo teve como objetivo analisar o aconselhamento em HIV/Aids realizado pelos profissionais do Centro de Testagem e Aconselhamento (CTA), na perspectiva educacional de Paulo Freire. Realizou-se um estudo descritivo com abordagem qualitativa e delineamento de investiga??o cr?tico-reflexiva, com base nos princ?pios da Ci?ncia-A??o. Participaram desta pesquisa todos os profissionais, totalizando oito, que atuam no aconselhamento no CTA de Jo?o Pessoa/PB. Os dados foram coletados no m?s de mar?o de 2011, por meio da observa??o n?o participativa e entrevista semiestruturada, com enfoque cr?tico-reflexivo, e analisados segundo os aportes da metodologia cr?tico-reflexiva e discutidos ? luz da pedagogia de Paulo Freire e autores pertinentes. Observou-se que a maioria dos profissionais compreende a filosofia de trabalho do CTA como sendo o diagn?stico e a preven??o associada ? utiliza??o e demonstra??o do preservativo. Contudo, ao observar as suas a??es durante os aconselhamentos, essas ideias se concretizam parcialmente. Temas educativos n?o foram abordados e o preservativo n?o foi oferecido em nenhum dos atendimentos. As a??es centraram-se no acolhimento de informa??es e no preenchimento dos formul?rios necess?rios ao atendimento, com di?logo breve e com pouca abertura para o usu?rio expor, ou completar, os seus pensamentos e necessidades. Os profissionais citaram as condi??es facilitadoras para o aconselhamento, a intera??o da equipe e estrutura f?sica. Focalizaram as dificuldades do baixo grau de cogni??o dos usu?rios, a demanda de atendimentos e outros aspectos da organiza??o de servi?o, e o descompromisso dos aconselhadores quanto ?s faltas e atrasos. Ao refletir sobre as a??es observadas nos aconselhamentos, a maioria dos profissionais reconheceu que precisa modificar algumas a??es do atendimento para incorpora??o dos princ?pios educativos na realiza??o de uma preven??o mais ampla, e se mostraram dispostos a trabalhar nessa perspectiva. Conclui-se que, embora os profissionais expressem ideias condizentes com os prop?sitos do CTA, estas s?o limitadas como apropria??o do significado de preven??o em HIV/Aids. Na medida em que expressam uma compreens?o e agem de forma diferente na realiza??o das a??es durante o aconselhamento, demonstram a desarticula??o entre as teorias em uso e as teorias propostas, conforme os aportes da teoria da ci?ncia-a??o. O aconselhamento como pr?tica educativa se concretiza parcialmente nos atendimentos e a orienta??o para uma reflex?o ? pouco oportunizada no atendimento. Esses achados sugerem a necessidade de inserir o processo de reflex?o na realiza??o das a??es de aconselhamento, de forma que estas sejam pautadas na pr?tica reflexiva, objetivando a transforma??o do seu modo de pensar e agir para uma perspectiva educacional com vistas a uma assist?ncia mais democr?tica e integral.

Made available in DSpace on 2016-08-18T17:27:38Z (GMT). No. of bitstreams: 1 Dissertacao LUIS FERNANDO BOGEA PEREIRA.pdf: 908998 bytes, checksum: a39235dcff5d0b2b802f9a1440dd8254 (MD5) Previous issue date: 2014-04-28 / In 2007 were estimated 9.27 million TB cases, 1.4 million of these were also seropositive for HIV. That same year were 456 000 registered cases of deaths from TB who were also infected with HIV. The association between tuberculosis (TB) and HIV infection affects mortality in two ways: TB presents significant lethality for people infected with HIV, and HIV acts as an indirect cause of the increased incidence of TB. Has to analyze the prevalence and factors associated with TB / HIV in patients with tuberculosis in the state of Maranhão. We conducted a cross-sectional analytical study of time series of TB cases notified in the period 2001 to 2011 in the state of Maranhão, totaling 4,553 cases of tuberculosis. Information was collected from the database of State Department of State Health Information Disease Surveillance System (SINAN). To identify associations between outcome (TB / HIV) and the independent variables (age, sex, race / color, education, middle region, place of residence, clinical type, input type, foreclosure situation), we used regression Poisson with robust adjustment of variance. Prevalence ratios (PR) and the ranges of 95 % confidence intervals (95 % CI) were estimated. We found a prevalence of TB / HIV coinfection of 15,1 % in the state. The highest prevalence ranged from 52.9 % in 2001, 11.8% in 2011, and the minimum prevalence ranged of1, 8 % in 2001, 5.9% in 2011. The prevalence of anti - HIV tests ranged from 4.3 % in 2001, 65.9% in 2011. According to the crude analysis, the most significant associations for TB / HIV were males (p ≤ 0.001), age group 20-39 years (p = 0.003) and 40-59 years (p = 0.036) have ≤ 8anos study (p = 0.001), be transferred (p = 0.053), living on the west mesoregion state (p = 0.009) and have closure for oncompliance (p = 0.016) or death (p ≤ 0.001). In the adjusted analysis, both males, age 29-30 years ≤ 8 years, living in the middle region west of the state, like having closure due to death, proved significant for TB / HIV coinfection. On the other hand, the non-white category and Pulmonary TB is presented both as a protective factor in the crude analysis as adjusted, and age ≥ 60 years in only adjusted. High rate of TB / HIV in the state (15,1%), being clear that young males with low education may be contributing to this increase was observed. There needs to adopt specific strategies to monitor this clientele, seeking to reduce the rate of coinfection. / Em 2007 foram estimados 9,27 milhões de casos de TB no mundo, destes 1,4 milhão também eram soropositivos para o Vírus da Imunodeficiência Humana (HIV). Nesse mesmo ano foram registrados 456 mil casos de mortes por TB que também estavam infectados pelo HIV. A interação entre o Mycobacterium tuberculosis e o Vírus da Imunodeficiência Humana (HIV) afeta a mortalidade de duas formas: a TB traz uma importante letalidade para as pessoas infectadas pelo HIV, e o HIV atua como causa indireta do aumento da incidência da TB. Tem-se como objetivo analisar a prevalência e os fatores associados à coinfecção TB/HIV em portadores de tuberculose no estado do Maranhão. Realizou-se um estudo transversal analítico com os casos de TB notificados no período de 2001 a 2011 no estado do Maranhão, totalizando 4.553 casos . As informações foram coletadas a partir do banco de dados do Sistema de Informação de Agravos de Notificação (SINAN) da Secretaria de Estado de Saúde do Estado. Para identificar as associações entre desfecho (coinfecção TB/HIV) e as variáveis independentes (idade, sexo, raça/cor, escolaridade, mesorregião, zona de residência, forma clínica, tipo de entrada, situação de encerramento), utilizou-se a regressão de Poisson, com ajuste robusto da variância. Foram estimadas as razões de prevalência (RP) e os intervalos de 95% de confiança (IC 95%). Encontrou-se uma prevalência geral da coinfecção TB/HIV de 15,1% no Estado. A prevalência máxima variou de 52,9 % em 2001 a 11,8% em 2011, e a prevalência mínima variou de1,8 % em 2001 a 5,9% em 2011. A prevalência de testes anti-HIV realizados variou de 4,3% em 2001 a 65,9 % em 2011. De acordo com a análise bruta, as associações mais significativas para coinfecção TB/HIV foram o sexo masculino (p≤0,001), as faixas etárias de 20 a 39 anos (p=0,003) e 40 a 59 anos (p=0,036), ter ≤ 8anos de estudo (p=0,001), ser transferido (p=0,053), residir na mesorregião oeste do Estado (p=0,009) e ter encerramento por abandono (p=0,016) ou óbito (p≤0,001). Na análise ajustada, o sexo masculino, idade de 29 a 30 anos, ≤8 anos de estudo, residir na mesorregião Oeste do Estado, encerramento por óbito, permaneceram associados à coinfecção TB/HIV. Por outro lado, a categoria não branca e a forma clínica pulmonar apresentaram-se como fator protetor tanto na análise bruta como na ajustada, e a idade≥60 anos somente na ajustada. Foi observada alta taxa de coinfecção TB/HIV no Estado (15,1%), sendo nítido que jovens do sexo masculino com baixa escolaridade e o desfecho do tratamento por abandono ou óbito podem estar contribuindo para este aumento. Há necessidades de se adotar estratégias específicas de acompanhamento dessa clientela, buscando reduzir essa taxa de coinfecção.

O panorama epidemiológico da AIDS indica a expansão da epidemia entre mulheres e conseqüentemente a infecção de crianças através da transmissão vertical. As crianças acometidas pela AIDS podem apresentar diversos sintomas e sinais próprios da doença, entre eles, atraso no desenvolvimento neuropsicomotor. No entanto, crianças filhas de mães soropositivas mesmo quando não infectadas, podem sofrer as conseqüências da doença em sua família. Os objetivos deste estudo foram: comparar o desenvolvimento neuropsicomotor de crianças não infectadas filhas de mães soropositivas para o HIV com crianças não expostas ao vírus; identificar fatores para atraso no desenvolvimento destas crianças e refletir sobre a necessidade de intervenção pela terapia ocupacional. Foram comparados dois grupos, com 45 crianças em cada um deles, nas idades de 3, 8 e 18 meses. Em relação ao desenvolvimento neuropsicomotor não foram encontradas diferenças entre o grupo de crianças filhas de mães soropositivas para o HIV e crianças não expostas ao vírus nas idades em conjunto, porém foi encontrada diferença significativa entre eles na idade de 3 meses. Também foram encontradas diferenças significativas entre os grupos quando comparados quanto à renda familiar, ao peso da criança ao nascimento e ao hábito materno da utilização de drogas ilícitas. Contudo, aos 3 meses de idade, apenas o hábito materno da utilização de drogas ilícitas influenciou negativamente o desenvolvimento neuropsicomotor das crianças. Os resultados permitiram discutir o papel do terapeuta ocupacional junto a esta população e sugere-se que novos estudos envolvendo o tema poderão colaborar com a confirmação dos dados obtidos, bem como dar continuidade às reflexões sobre a atuação deste profissional. / The Aids epidemiological background indicates the spread of epidemic among women and consequentially the infection of children through vertical transmission. The HIV infected children can show several peculiar symptoms and signs of the disease, such as the delay in the neuropsychomotor development. Nevertheless, children born to HIV-infected women even when uninfected, might suffer the disease consequences in their family. The objectives of this study are: to compare neuropsychomotor development of uninfected children born to HIV-infected women to children not exposed to the virus; to identify factors that influence the delay of children development and discuss the need for intervention by Occupational Therapy. Comparing the group of children born to HIV-infected women to children not exposed (in each group were included 45 children), in the three studied ages (3, 8 e 18 months), no differences were found related to the neuropsychomotor development, but in the age of 3 months a significant difference was observed. Significant differences were also found among the groups when familiar income, at birth weight of children and maternal habits of illicit drug use were analyzed. However, in the age of 3 months, only the maternal habit of illicit drug use had negative effects in the neuropsychomotor development. According to the results, it’s possible to discuss the occupational therapist practice with this population and to suggest the need of new studies related to this subject that can contribute to the confirmation of the data and also continue the discussing about this professional actuation.

No abstract available. / Dissertation (LLM)--University of Pretoria, 2013. / gm2014 / Centre for Human Rights / unrestricted