Introdução: O emprego da terapia antirretroviral (TARV) proporcionou dramático impacto na mortalidade por aids e aumento na sobrevida. Entretanto, esse panorama depende da manutenção de altas taxas de adesão ao tratamento medicamentoso. A relevância da adesão tem sido reconhecida pelo Programa Nacional de DST e Aids desde o final dos anos 1990. Em que pese o destaque que o plano propositivo do Programa tem dado para a questão, ainda não dispõe de estudo atualizado sobre o número e tipo das atividades que estão em curso nos serviços. Este estudo teve por objetivo descrever as atividades de adesão em curso nos serviços de HIV/aids do Estado de São Paulo. Métodos: Foi enviado um questionário semi-estruturado para todos os 179 ambulatórios de HIV/aids do Estado, com perguntas sobre o tipo de serviço, pessoas sob TARV, formas e frequências de avaliação de adesão, atividades desenvolvidas (individuais, coletivas e para grupos específicos) e parcerias com organizações não governamentais. Para testar associação entre variáveis categóricas utilizou-se o teste Qui-quadrado de Pearson ou os testes exato de Fisher ou teste da razão de verossimilhanças, no nível de significância de p<0,05. A análise de agrupamento foi utilizada para investigar cada uma das associações de cada resposta com as variáveis: tamanho do município, tipo e tamanho das clínicas. Resultados: 136 dos ambulatório (76%) responderam à pesquisa. Quase todos (96,3%) relataram incentivar a adesão na prática clínica, predominantemente nas consultas de médicos (94,1%) e enfermeiros (67,6%). A maioria (78,7%) relatou avaliar a adesão através de registros da farmácia. Grupos (38,2%) e palestras (28,7%) foram as atividades de grupo mais conduzidas. A análise de agrupamento identificou três grupos de ambulatórios, dois deles muito distintos. Grupo 1 (27 ambulatórios) foi composto predominantemente por unidades de saúde básica, com menos de 100 pacientes, apresentaram a menor freqüência de avaliação da adesão e menos atividades individuais e em grupo. Grupo 2 (51 ambulatórios) foi constituído principalmente por ambulatórios especializados em HIV/aids, com mais de 500 pacientes, com maior freqüência de avaliação da adesão, maior participação de psicólogos, assistentes sociais e farmacêuticos e mais atividades individuais e em grupo. Grupo 3 (56 ambulatórios) foi composto em sua maioria por ambulatórios de especialidades e de médio porte, com a maioria das atividades semelhantes ao Grupo 2, exceto pela ausência de atividades para grupos específicos e menos envolvimento multidisciplinar. Conclusão: Dado o amplo reconhecimento da importância da adesão por parte das clínicas, ainda há poucas atividades específicas de adesão no Estado. As clínicas maiores e mais especializadas tendem a oferecer mais atividades individuais e em grupo, utilizando abordagens multidisciplinares. Maior atenção deve ser dada para a descentralização do atendimento às pessoas vivendo com HIV para assegurar cuidados de qualidade mais homogêneos em toda a rede ambulatorial. / Introduction: The use of antiretroviral therapy (HAART) has provided dramatic impact on AIDS mortality and improved survival. However, this scenario depends on maintaining high rates of adherence to HAART. The relevance of adherence has been recognized by the National STD/AIDS Program since the late 1990s. Despite the emphasis that the Program has given to the issue, there have been no study to date on the number and type of activities that are underway in the services. This study aimed to describe the HAART adherence support activities in Sao Paulo State HIV/AIDS clinics. Methods: We sent a semi structured questionnaire to all 179 HIV/AIDS clinics with questions about type of clinic, people on HAART, adherence assessment, activities (individual, group and for specific groups). To test association between categorical variables used the chi-square test or Fisher exact test or likelihood ratio test at a significance level of p <0.05. Cluster analysis was used to investigate each association of each answer with the variables: municipality size, type and size of the clinics. Results: 136 clinics (76%) answered the survey. Almost all (96.3%) reported encouraging adherence in clinical practice, particularly in the medical (94.1%) and nurse (67.6%) visits. Most (78,7%), reported assessing adherence by pharmaceutical records. Groups (38.2%) and lectures (28.7%) were the group activities most developed. Cluster analysis identified three groups of clinics; two of them were too different. Group 1 (27 clinics) was predominately composed by primary care clinics, with less than 100 patients, the lowest frequency of assessing adherence and fewer individual and group activities. Group 2 (51 clinics) predominately composed by HIV specialized clinics specializing, HIV/AIDS, with more than 500 patients, assessing adherence more frequently, with greater involvement of psychologists, social workers and pharmacists developing more individual and group activities. Group 3 (56 clinics) was predominately composed by medium size specialized clinics, with majority of activities similar to Group 2, except by the absence of activities to specific groups and less multidisciplinary involvement. Conclusion: Given the broad recognition of the adherence importance by the clinics, there are still few specific adherence activities. The larger and more specialized clinics tend to provide more individual and group activities, using multidisciplinary approaches. Greater attention should be given to the decentralization of care offered to people living with HIV to ensure more homogeneous quality care across the ambulatory network.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Background: Despite the effort of scientific research on HIV therapies and to reduce the rate of HIV infection, AIDS remains one of the major causes of death in the world and mostly in sub-Saharan Africa. To date, neither a cure nor an HIV vaccine had been found and the disease can only be managed by using High Active Antiretroviral Therapy (HAART) if detected early. The need for an effective early diagnostic and non-toxic treatment has brought about the necessity for the discovery of additional HIV diagnostic methods and treatment regimens to lower mortality rates. Antimicrobial Peptides (AMPs) are components of the first line of defense of prokaryotes and eukaryotes and have been proven to be promising therapeutic agents against HIV. Methods: With the utility of computational biology, this work proposes the use of profile search methods combined with structural modeling to identify putative AMPs with diagnostic and anti-HIV activity. Firstly, experimentally validated anti-HIV AMPs were retrieved from various publicly available AMP databases, APD, CAMP, Bactibase and UniProtKB and classified according to super-families. Hidden Markov Model (HMMER) and Gap Local Alignment of Motifs (GLAM2) profiles were built for each super-family of anti- HIV AMPs. Putative anti-HIV AMPs were identified after scanning genome sequence databases using the trained models, retrieved AMPs, and ranked based on their E-values. The 3-D structures of the 10 peptides that were ranked highest were predicted using 1-TASSER. These peptides were docked against various HIV proteins using PatchDock and putative AMPs showing the highest affinity and having the correct orientation to the HIV -1 proteins gp120 and p24 were selected for future work to establish their function in HIV therapy and diagnosis. Results: The results of the in silica analysis showed that the constructed models using the HMMER algorithm had better performances compare to that of the models built by the GLAM2 algorithm. Furthermore, the former tool has a better statistical and probability explanation compared to the latter tool. Thus only the HMMER scanning results were considered for further study. Out of 1059 species scanned by the HMMER models, 30 putative anti-HIV AMPs were identified from genome scans with the family-specific profile models after the elimination of duplicate peptides. Docking analysis of putative AMPs against HIV proteins showed that from the 10 best performing anti-HIV AMPs with the highest E-scores, molecules 1,3, 8, and 10 firmly bind the gp120 binding pocket at the VIN2 domain and the point of interaction between gp120 and T cells, with the 1st and 3rd highest scoring anti-HIV AMPs having the highest binding affinities. However, all 10 putative anti-HIV AMPs bind to the N-terminal domain of p24 with large surface interaction, rather than the C-terminal. Conclusion: The in silica approach has made it possible to construct computational models having high performances, and which enabled the identification of putative anti-HIV peptides from genome sequence scans. The in silica validation of these putative peptides through docking studies has shown that some of these AMPs may be involved in HIV/AIDS therapeutics and diagnostics. The molecular validation of these findings will be the way forward for the development of an early diagnostic tool and as a consequence initiate early treatment. This will prevent the invasion of the immune system by blocking the VIN2 domain and thus designing of a successful vaccine with broad neutralizing activity against this domain.

MSc (Mathematcs) / Department of Mathematics and Applied Mathematics / Infectious diseases remain a major public health concern. Well-known for causing sickness and death, enormous pain and suffering, increased time spent on patient care and huge economic losses due to lost production. Infectious diseases continue to be a scourge without equal. In this work, we address the following research question: Can we use a multiscale model of HIV/AIDS transmission dynamics to assess the comparative effectiveness of health interventions that are implemented at different scale domains? To achieve the set objectives of the study, we use multiscale modelling approach, a new and emerging computational high-throughput technique for mathematically studying problems that have many characteristics across several scales. To be more specific, we perform three tasks in addressing the research question. First, we develop a within-host submodel and use it to show it’s associated limitations which only a multiscale model can resolve. Second, we develop a between-host submodel and use it to motivate the need for multiscale modelling of the HIV/AIDS disease system. Finally, we link the two submodels to produce a nested HIV/AIDS multiscale model that affords us the opportunity to compare effectiveness of five preventive and treatment HIV/AIDS health interventions. Analysis of the multiscale model shows that it is possible to jointly study two key aspects (immunology and epidemiology) of infectious diseases. The multiscale model provides the means for making meaningful comparative effectiveness on available preventive and treatment health interventions. Consequently, we employ the multiscale model to show that impact of HIV/AIDS packages increases as more interventions are integrated into the packages. Specifically, the study shows that combined HAART and male circumcision is more effective than an intervention involving HAART alone. Overall, our study successfully illustrates the utility of multiscale modelling methodology as a tool for assessing the comparative effectiveness of HIV/AIDS preventive and treatment interventions. For purposes of informing public health policy, we use the study results to infer that condom use, male circumcision and pre-exposure prophylaxis are more effective in controlling the transmission dynamics of HIV/AIDS at the start of the epidemic as compared to when the disease is endemic in the community while the converse is also true for HAART. / NRF

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Adolescence is a significant period of change in physical and psychosocial development of human beings. Being HIV positive and growing up on a dynamically multifaceted HAART treatment, adds to the complexity of adolescence. This study was aimed at exploring the nature of experiences of adolescents who are on long-term Highly Active Antiretroviral Therapy (HAART) in Tembisa, Gauteng province. The study is based on a qualitative research method using in-depth semi-structured open-ended interviews and a focus group for data collection. The sample consisted of seven individual adolescent participants, three parents, guardians and caregivers, as well as 11 health care professionals. The thematic data analysis and the phenomelogical analysis methods were used to analyse data qualitative data while descriptive statistics were used to analyse quantitative biographical data. The study findings cover the negative and positive experiences and the perceived role of HAART treatment over a long period of time. The predominant themes identified from adolescent participants were disclosure of HIV positive status and the stigma surrounding a positive status, early childhood experience of parental death, challenges of taking HAART treatment, factors influencing adherence and non-adherence to HAART treatment, and lastly, the impact of religion on HAART treatment adherence. The findings suggest that adolescents who are on HAART treatment over an extended period of time experience drug fatigue. Drug fatigue has far-reaching implications for the health of an adolescent, as it has a higher likelihood that poor adherence or even complete refusal to take HAART treatment will occur. Poor adherence or refusal to take HAART treatment will most likely lead to cross infection and further spread of HIV and AIDS. A recommendation was made to include the establishment of a youth and adolescent-friendly centre by the hospital – one that is designated for the provision of tailored adolescent services and sensitive to adolescent developmental stages so as to minimise the likelihood of infected adolescents falling through the health care cracks. The introduction of a hospital-based school, an education unit run by dedicated and qualified facilitators focusing on aiding hospitalised learners with catch-up scholarly programmes, was a further recommendation. It was further recommended that reproductive health care needs of adolescents who grow up on HAART treatment be given attention in further research. / Psychology / Ph.D. (Psychology)

This study analysed data obtained from respondents and their medical records to determine the barriers and motivators for good adherence to ART. Respondents' records were also reviewed together with their pharmacy refill records to identify any correlation between .CD4 cell counts, viral load, VL and adherence to antiretroviral drugs at extension 15 ARV clinic in Gaborone, Botswana. The study investigated whether the combination of pharmacy refills and pill counts adherence measurement methodologies could predict immunological recovery and virologic response through increased CD4 cell counts and suppressed VL. . There was a positive relationship between adherence, CD4 cell counts and VL. Pharmacy refills and pill counts adherence measurement methodologies scored high on sensitivity, specificity, and positive predictive values but low on negative predictive values. / Health Studies / M.A. (Public Health)

Submitted by Paulo Junior (paulo.jr@fgv.br) on 2010-05-13T21:02:37Z No. of bitstreams: 1 Cláudia Hoirisch.pdf: 1193444 bytes, checksum: 18921b0201a6008cb606c1dcc39797a0 (MD5) / Approved for entry into archive by Paulo Junior(paulo.jr@fgv.br) on 2010-05-13T21:03:02Z (GMT) No. of bitstreams: 1 Cláudia Hoirisch.pdf: 1193444 bytes, checksum: 18921b0201a6008cb606c1dcc39797a0 (MD5) / Made available in DSpace on 2010-05-14T12:29:32Z (GMT). No. of bitstreams: 1 Cláudia Hoirisch.pdf: 1193444 bytes, checksum: 18921b0201a6008cb606c1dcc39797a0 (MD5) Previous issue date: 2010-03-24 / The scope of this study is to evaluate the implementation process of the Compulsory License in the case of the antiretroviral efavirenz. This research is descriptive in nature and the medium of investigation was the case study. It was conducted during the months of October through December 2009 with semi-structured interviews containing open-ended questions with a group of Public Health policy makers and managers residing in the states of Rio de Janeiro, Sao Paulo and the Federal District who participated in the compulsory license process. These individuals were allowed to express themselves without any constraints in such a way that they could produce discourses. The Collective Subject Discourse (CSD) technique was then used for analysis of the discourses. The results revealed that Brazil has the technological capability to develop and produce antiretrovirals within a reasonably short period of time. The results further showed that the Compulsory License helped to curb spending on antiretrovirals and that the measure can be used to ensure access by the public to high-cost and strategic antiretroviral drugs for the Brazilian public health service (Unified Health System – SUS) in an environment with limited funds, whenever an impasse is reached in negotiations for price reductions with transnational pharmaceutical laboratories. / O objetivo deste estudo é avaliar o processo de implementação da Licença Compulsória no caso do anti-retroviral efavirenz. Esta pesquisa é de caráter descritivo, o meio de investigação foi o estudo de caso e foi conduzido com entrevistas semi-estruturadas contendo questões abertas para um conjunto de atores representativos da área da Saúde Pública que participaram do processo da licença compulsória residentes nos estados do Rio de Janeiro e São Paulo e no Distrito Federal durante os meses de outubro a dezembro de 2009. Permitiu-se que esses indivíduos se expressassem mais ou menos livremente de forma que eles produzissem discursos. Para a análise dos discursos, utilizou-se a técnica do Discurso do Sujeito Coletivo (DSC). Os resultados demonstraram que o Brasil possui capacitação tecnológica para desenvolver e produzir anti-retrovirais em um prazo relativamente curto. Os resultados mostram ainda que a Licença Compulsória ajudou a refrear os gastos com anti-retrovirais e que o instrumento pode ser utilizado para garantir o acesso da população a medicamentos anti-retrovirais de alto custo e estratégicos para o Sistema Único de Saúde em um ambiente de recursos limitados sempre que se chegar a um impasse na negociação para redução de preços com os laboratórios farmacêuticos transnacionais.

This study analysed data obtained from respondents and their medical records to determine the barriers and motivators for good adherence to ART. Respondents' records were also reviewed together with their pharmacy refill records to identify any correlation between .CD4 cell counts, viral load, VL and adherence to antiretroviral drugs at extension 15 ARV clinic in Gaborone, Botswana. The study investigated whether the combination of pharmacy refills and pill counts adherence measurement methodologies could predict immunological recovery and virologic response through increased CD4 cell counts and suppressed VL. . There was a positive relationship between adherence, CD4 cell counts and VL. Pharmacy refills and pill counts adherence measurement methodologies scored high on sensitivity, specificity, and positive predictive values but low on negative predictive values. / Health Studies / M.A. (Public Health)