Orientador: Sandra Cecilia Botelho Costa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-15T04:01:32Z (GMT). No. of bitstreams: 1 Anjos_EmanuelBorgesVitor_M.pdf: 3213507 bytes, checksum: e3dcff33af728ca20ad8aaf6a15893b6 (MD5) Previous issue date: 2009 / Resumo: A infecção pelo HIV está entre as principais causas de inaptidão definitiva para doação de sangue. A dinâmica natural da epidemia do HIV no Brasil levou-nos a avaliar os subtipos presentes do HIV-1 em doações de sangue com infecção pelo HIV. Doadores de sangue representam um amplo e melhor corte transversal da população do que em grupos selecionados de alto risco e, portanto, podem fornecer uma visão mais ampla das cepas circulantes do HIV-1 no Brasil. Os números de indivíduos infectados e a importância da infecção pelo HIV tornam esse vírus um importante problema de saúde pública no Brasil. O objetivo deste trabalho é estudar a epidemiologia molecular do HIV-1 em candidatos a doadores de sangue da Fundação Hemope (Pernambuco), a partir da confirmação da infecção pelo HIV-1 de doadores com status sorológico positivo ou indeterminados pela Reação em Cadeia da Polimerase (PCR). Também avaliar a co-infecção do HIV-1 com outros patógenos que são avaliados na triagem sorológica. Dos 328 doadores de sangue com sorologia positiva ou inconclusiva coletados, foram confirmados 46 (14,02%) como positivos para HIV. Destas 46 amostras, foi possível realizar a subtipagem do HIV-1 em 40 amostras, sendo 35 (87.50%) amostras do subtipo B, 4 (10%) do subtipo C e 1 (2.50%) da forma recombinante CRF02_AG. Investigação por métodos moleculares indica ser decisiva na interpretação definitiva do diagnóstico para o HIV. Estudos de epidemiologia molecular do HIV-1 junto com o entendimento de sua biologia são necessários para estudar a dinâmica da infecção e para guiar políticas sanitárias para controlar a expansão do vírus e reduzir a incidência mundial da AIDS. / Abstract: HIV infection is among the leading causes of permanent disability for donation of blood. The natural dynamics of the HIV epidemic in Brazil has led us to evaluate the present subtypes of HIV-1 in blood donations with HIV infection. Blood donors represent a wide cross section of the population than selected groups of high risk and therefore may provide a broader view of circulating strains of HIV-1 in Brazil. The numbers of infected individuals and the importance of HIV infection make this virus an important public health problem in Brazil. The objective of this work is to study the molecular epidemiology of HIV-1 candidate in the blood donors of the Foundation Hemope (Pernambuco), from the confirmation of HIV-1 serological status of donors with positive or indeterminate by the Polymerase Chain Reaction (PCR). Also assess co-infection of HIV-1 with other pathogens that are evaluated in serological screening. Of the 328 blood donors with positive serology or inconclusive collected, 46 were confirmed (14.02%) as positive for HIV. Of these 46 samples, it was possible to subtyping of HIV-1 in 40 samples, and 35 (87.50%) samples of subtype B, 4 (10%) of subtype C and 1 (2.50%) of the form recombinant CRF02_AG. Research shows by molecular methods be decisive in the interpretation of the final diagnosis for HIV. Studies of molecular epidemiology of HIV-1 with the understanding of its biology are needed to study the dynamics of infection and to guide health policies to control the spread of the virus and reduce the incidence of AIDS worldwide. / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

Sabe-se que o vírus da imunodeficiência humana (HIV) pode modificar a história natural da infecção pelo HCV, acelerando a progressão da fibrose hepática e conseqüente evolução para cirrose. O tratamento com interferon-alfa pode levar à melhora da histologia hepática, reduzindo a inflamação e fibrose, principalmente nos pacientes que apresentam resposta virológica sustentada. O impacto do tratamento sobre a evolução histológica em pacientes não-respondedores ao tratamento da hepatite C apresenta resultados controversos. Objetivos: Avaliar, nos pacientes com hepatite C crônica, co-infectados pelo HIV, o impacto do tratamento da hepatite C, sobre as modificações de parâmetros indicativos de fibrose e atividade inflamatória, em biópsias de fígado realizadas antes e após o tratamento da hepatite C. Métodos: Foram estudados 26 pacientes co-infectados pelo HCV e HIV-1, submetidos à biópsia hepática antes e, em média, 25,2 meses após o término do tratamento da hepatite C. Fragmentos da biópsia hepática foram comparados, antes e após o tratamento, em relação aos seguintes parâmetros: Índice de Atividade Histológica (HAI) e o grau de Fibrose (Knodell); intensidade do depósito de colágeno (coloração pelo picrosirius) e o grau de ativação das células estreladas (marcação com alfa-actina de músculo liso). Os índices destas variáveis histológicas, pós e pré-tratamento, foram relacionadas com o resultado do teste qualitativo RNA HCV (RT-PCR-AMPLICOR?) na 24a semana de tratamento, com a duração do tratamento da hepatite C e com o intervalo de tempo entre a interrupção do tratamento e a biópsia-controle. Foi avaliada a relação de possíveis fatores prognósticos de resposta virológica com a resposta histológica e foram realizadas correlações dos parâmetros histológicos entre si. Resultados: Os parâmetros histológicos avaliados de forma global foram semelhantes nas biópsias pré e pós-tratamento. As razões pós/pré-tratamento, em todos os parâmetros avaliados nas biópsias hepáticas, diminuíram de forma significativa nos pacientes que apresentaram pesquisa negativa para o RNA HCV na 24ª semana de tratamento. Os parâmetros histológicos foram semelhantes nos grupos com duração de tratamentos diferentes (? 24 semanas e > 24 semanas), exceto as CEH células ?-positivas, que teve melhora no grupo com tratamento mais prolongado. O intervalo de tempo entre o final do tratamento e a biópsia-controle não influenciou a melhora histológica. Na análise de regressão logística, houve associação da melhora dos parâmetros histológicos com o resultado negativo do RNA HCV na 24ª semana de tratamento. Houve correlação significativa entre todos os parâmetros histológicos avaliados. Conclusões: Os pacientes avaliados em conjunto tiveram seus parâmetros histológicos nas biópsias pré e pós-tratamento com valores semelhantes, porém quando se definiu melhora histológica, como a manutenção, ou melhora dos parâmetros histológicos avaliados individualmente, verificou-se que uma substancial parcela da população estudada apresentou melhora histológica. O efeito benéfico do tratamento parece se relacionar com o controle da viremia do HCV durante o tratamento e se verifica também em pacientes que não sustentaram a resposta virológica após a suspensão dos medicamentos. Os achados fazem supor que a redução da viremia do HCV teria como conseqüência a diminuição da inflamação e fibrose hepáticas, inclusive com diminuição do estado de ativação das células estreladas hepáticas, mesmo nos casos em que não houve resposta virológica sustentada. Os resultados do presente estudo são sugestivos de que o tratamento da hepatite C pode modificar a história natural da evolução da hepatite crônica nos pacientes co-infectados pelo HIV. / Human immunodeficiency virus (HIV) is known to be able to modify the natural history of HCV infection, accelerating the progression of hepatic fibrosis and the consequent evolution to cirrhosis. Treatment with interferon-alpha can lead to improved hepatic histology, reducing inflammation and fibrosis, especially in patients who present a sustained virologic response. The impact of treatment on histological evolution in patients who do not respond to treatment of hepatitis C is a controversial matter. Objectives: To evaluate in patients with chronic hepatitis C co-infected with HIV the impact of treatment of hepatitis C on the modifications of the parameters indicative of fibrosis and of inflammatory activity in liver biopsies obtained before and after treatment of hepatitis C. Methods: Twenty-six patients co-infected with HCV and HIV-1 were submitted to a liver biopsy before and, on average, 25.2 months after the end of treatment of hepatitis C. Fragments of the liver biopsy were compared before and after treatment regarding the following parameters: histological activity index (HAI) and grade of fibrosis (Knodell); intensity of collagen deposition (picrosirius staining), and grade of stellate cell activation (labeling with smooth muscle alpha-actin). The post- and pretreatment ratios of these histological variables were related to the result of the quantitative HCV-RNA test (RT-PCR-AMPLICOR?) during the 24th week of treatment, to the duration of treatment of hepatitis C and to the time interval between the discontinuation of treatment and the control biopsy. The relationship between possible factors of the virologic response and the histological response was evaluated and correlations between the various histological parameters were calculated. Results: The histological parameters evaluated in a global manner were similar in the pre- and post-treatment biopsies. The post-pretreatment ratios for all parameters evaluated in the liver biopsies were significantly reduced in patients who were negative for HCV RNA during the 24th week of treatment. The histological parameters were similar in the groups with different durations of treatment (? 24 weeks and > 24 weeks), except for ?-positive stellate hepatic cells, which were improved in the group with a more prolonged treatment. The time interval between the end of treatment and the control biopsy did not affect the histological improvement. In logistic regression analysis, the improvement of the histological parameters was found to be associated with a negative result of HCV RNA during the 24th week of treatment. There was a significant correlation between all histological parameters evaluated. Conclusions: When evaluated as a whole, the patients showed similar values for their histological parameters in the pre- and post-treatment biopsies. However, when histological improvement was defined as the maintenance or improvement of the histological parameters evaluated individually, a substantial part of the study population was found to present histological improvement. The beneficial effect of treatment seemed to be related to the control of HCV viremia during treatment and was also observed in patients who did not sustain the virologic response after the discontinuation of the medications. These findings lead us to assume that the reduction of HCV viremia causes a reduction of hepatic inflammation and fibrosis, as well as a reduction of the state of activation of stellate hepatic cells even in cases in which there is no sustained virologic response. The results of the present study suggest that treatment of hepatitis C can modify the natural history of the course of chronic hepatitis in patients co-infected with HIV.

A implementação da integralidade é um grande desafio à consolidação do Sistema Único de Saúde e a vulnerabilidade na Atenção Básica às DST/HIV/aids foi o objeto deste estudo, cujos objetivos foram: caracterizar as Unidades Básicas de Saúde (UBS) segundo as Coordenadorias Regionais de Saúde, as Supervisões Técnicas de Saúde, os modelos de organização da atenção à saúde, as Organizações Sociais de Saúde em contratos de gestão na cogestão da saúde com a Secretaria Municipal de Saúde de São Paulo e a formação profissional do gerente; identificar o grau de Vulnerabilidade Programática das UBS e discuti-lo segundo os componentes: acessibilidade, porta de entrada, vínculo, enfoque familiar, profissionais da saúde e coordenação/integração. A perspectiva conceitual utilizada foi da vulnerabilidade, em sua dimensão programática. Realizou-se estudo descritivo transversal com abordagem quantitativa, tendo sido utilizado um questionário com 51 questões, aplicado online, na plataforma FormSUS, com gerentes das 442 UBS do Município de São Paulo. Foram obtidas respostas de 328 gerentes das UBS; 40,9% eram exclusivas \"tradicionais\"; 55,8% das OSS eram do tipo \"Associação\" e mais da metade dos gerentes das UBS eram Enfermeiros. Há graus diferenciados de vulnerabilidade programático, mas de um modo geral nas UBS é baixo. Há vulnerabilidade na efetivação da integralidade: falta de materiais para atividades educativas; baixa oferta de testes de detecção de sífilis à gestante e teste anti- HIV no pré-natal; demora no retorno do resultado do exame anti-HIV; baixa indicação do tratamento com Penicilina Benzatina ao parceiro da gestante com diagnóstico de sífilis; não realização da abordagem consentida para solicitação de teste para HIV à gestante ou para a população geral; falta de capacitação para realização da abordagem sindrômica das DST e aconselhamento na oferta do teste do HIV; falta de contrarreferência às UBS, DST/aids. Conclui-se que a integralidade traduzida em práticas de saúde na atenção às DST/HIV/aids possibilitou visualizar as vulnerabilidades programáticas nas UBS e apontou desafios para sua efetivação. / Implementation of comprehensive attention is a huge challenge in the consolidation of the Brazilian Unified Health System. The vulnerability to STD/HIV/Aids in Primary Care was focused on this study, aiming to provide tools to improve healthcare. The objectives of the study were: 1) to characterize Primary Care Units (PCU) according to selected variables such as: administrative hierarchy position (Regional Health Coordination, Healthcare Technical Supervision), administrative issues (models healthcare attention of organization, Healthcare Social Organization (HSO) in management or co-management with the Township Healthcare Office in São Paulo), and manager formal professional qualification; 2) to identify the level of Programmatic Vulnerability; and 3) to assess the Programmatic Vulnerability according to the following components: accessibility, point of entry, links, family approach, health professional and integration / coordination. The conceptual approach was the vulnerability in its programmatic dimension. This was a transversal descriptive and quantitative study based on an online survey with 51 questions applied in the FormSUS platform and involving managers from 442 PCU of the city of São Paulo. Responses were received from 328 PCU managers; among them more than half were Nurses. PCU were exclusively \"conventional in 40.9% and 55.8% of the HSO were classified as \"association\". There were different levels of programmatic vulnerability; in general however, the vulnerability was low. There was vulnerability in making comprehensive attention effective: lacking of material for educational activities; insufficiency of availability of tests to detect syphilis in pregnant women and anti-HIV test in the pre-natal period; excessive delay in results of anti-HIV tests causing them to be not time-opportune; low practice of indication of syphilis treatment with Benzathine Penicillin for the pregnant partner; lacking of informed consent to request HIV testing to pregnant women as well general population; lacking of training for the syndromic approach to STDs; lacking of counseling when offering HIV testing; lacking of counter-reference to PCU, STD/Aids. It was concluded that the translation of the comprehensiveness concept into health practices regarding STD/HIV/aids enabled us to assess programmatic vulnerabilities in the PCU, and pointed out challenges to achieve a true comprehensive healthcare attention.

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-04-18T10:56:17Z No. of bitstreams: 1 rodrigodemartinalmeida.pdf: 1545092 bytes, checksum: 867683f208ae95160982b0697b1b73c3 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-04-20T12:47:44Z (GMT) No. of bitstreams: 1 rodrigodemartinalmeida.pdf: 1545092 bytes, checksum: 867683f208ae95160982b0697b1b73c3 (MD5) / Made available in DSpace on 2018-04-20T12:47:44Z (GMT). No. of bitstreams: 1 rodrigodemartinalmeida.pdf: 1545092 bytes, checksum: 867683f208ae95160982b0697b1b73c3 (MD5) Previous issue date: 2015-02-26 / A tuberculose (TB) é uma doença existente há milhares de anos e estima-se que um terço da humanidade esteja infectada pelo bacilo da doença, com mais de oito milhões de casos novos ao ano. O aumento do número de casos de TB se deve a fatores diversos, como as condições de moradia e outros Determinantes Sociais da Saúde, mas nada modificou tanto sua evolução como a pandemia do vírus da imunodeficiência humana (HIV). A associação desta co-infecção é sinérgica, interativa e recíproca, impactando no curso das duas patologias. A taxa média global de co-infeccção está entre 9 e 18%, embora encontrem-se taxas de até 80% na África. Percebe-se, todavia, baixa cobertura do exame anti-HIV no Brasil, entre outros fatores, porque o exame só é realizado mediante autorização do paciente. Este estudo transversal objetivou descrever a população de pacientes (n=231) com TB, no período de março de 2008 a fevereiro de 2010, atendidos em centros de referência em Juiz de Fora, município com a segunda maior prevalência de TB do estado de Minas Gerais, além de estimar a prevalência de HIV nesses pacientes, estratificando-os de acordo com 3 blocos de variáveis: uso de drogas, de comportamento sexual e socioeconômicas, avaliando os possíveis fatores associados à co-infecção e maior vulnerabilidade, através de dados de um questionário estruturado. Mais de dois terços dos pacientes do estudo eram do sexo masculino, a maior parte da amostra era negra ou parda e mais de 90% da amostra estava na faixa etária economicamente produtiva. A sorologia para HIV detectou 13,0% de co-infecção para o total do estudo e 18,1% quando se descartam os dados ignorados (28,1% dos pacientes sem resultado de HIV por diferentes motivos). As variáveis que mostraram associação com HIV positivo (p≤0,10) na análise bivariada foram o tipo de moradia, condição de ocupação, estado civil, número de parceiros sexuais ao longo da vida, orientação sexual, tabagismo, alcoolismo, uso de drogas ilícitas e uso de drogas injetáveis. Essas variáveis foram incluídas no modelo de regressão logística binária hierarquizado por blocos- uso de drogas, comportamento sexual e socioeconômicas, nessa ordem. No modelo final, mostraram-se significativas o uso de drogas injetáveis, o número de parceiros sexuais ao longo da vida e a condição de ocupação (p≤0,05). Pacientes que nunca trabalharam ou não estavam trabalhando apresentaram risco aumentado para HIV, (OR= 7,49 IC 95% 1,17- 47,9) em relação aos que trabalhavam. Pacientes que tiveram entre 4 e 9 parceiros apresentaram maiores riscos quando comparados aos que tiveram entre nenhum e 3 parceiros (OR= 26,7 IC95% 1,95 - 365,4), e, quanto ao uso de drogas injetáveis, os usuários apresentaram maiores riscos que os não usuários (OR= 26,0 IC95% 1,43- 472,4). O modelo final apresentou uma variável de cada bloco, reforçando a interconexão entre os fatores que geram a associação HIV/TB. Portanto, o processo de co-infecção deve e precisa ser visto de forma multifatorial e abranger ações sociais e políticas, especialmente quanto à realização da sorologia para HIV, tanto para evitar o crescimento das taxas de incidência e prevalência, quanto para o cuidado dos pacientes já co-infectados, trazendo melhorias à Saúde Coletiva. / Tuberculosis (TB) is a disease existing for thousands of years and it is estimated that one third of humanity is infected with the bacillus of the disease, with more than eight million new cases a year. The increase in the number of TB cases is due to several factors, such as quality of housing and other social determinants of health, but nothing changed its evolution as the pandemic of human immunodeficiency virus (HIV). The co-infection is synergic, interactive and has a reciprocal impact on the course of both diseases. The overall average rate of co-infection is between 9 and 18%, rates of up to 80% are found in Africa. It is well-known, however, the reality of low coverage of HIV testing in Brazil, among other factors, because the examination is carried out only after the authorization of the patient. This cross-sectional study aimed to describe the patient population (n = 231) with TB, from March 2008 to February 2010, seen at referral centers in Juiz de Fora, a city with the second highest prevalence of TB in the state of Minas Gerais, and estimate the prevalence of HIV in these patients, stratifying them according to three blocks of variables: drug use, sexual behavior and socioeconomic status, evaluating the possible factors associated with co-infection and increased vulnerability through data obtained from a structured questionnaire. More than two thirds of the study patients were male, the majority of the sample was black or brown and more than 90% of the sample was in the economically productive age group. The HIV test detected 13.0% of co-infection for the total study (28.1% of patients without the HIV test result, were considered) and 18.1% when missing data were discarded. The variables associated with HIV (p≤0,10) in the bivariate analysis were the type of housing, employment status, marital status, number of sexual partners over a lifetime, sexual orientation, smoking, alcoholism, illicit drug use and injection drug use. These variables were included in the regression model, a multiple covariates dichotomous logistic model with hierarchical blocks - by drug use, sexual behavior and socioeconomic status, in that order. In the final model, the following variables were significant: use of injectable drugs, the number of sexual partners over a lifetime and the occupation (p ≤ 0.05). Patients who have never worked or were not working presented an increased risk for HIV (OR = 7.49 95% CI 1.17- 47.9) than those who worked. Patients who had between 4 to 9 partners had higher risk compared to those who had none and between 3 partners (OR = 26.7 95% CI 1.95 to 365.4) and on the use of injectiable drug users had higher risk than nonusers (OR = 26.0 95% CI 1.43- 472.4). The final model showed a variable of each block, reinforcing the interconnection between the factors that generate the HIV / TB association. Therefore, the co-infection should and must be seen in a multidisciplinary way and address social and political actions, especially the performance of HIV serology, both to prevent the growth of the incidence and prevalence rates, as for patient care already co-infected, bringing improvements to Public Health.

Tuberculosis (TB) remains the main cause of death in people living with HIV (PLHIV). Indeed, PLHIV have a 20-30% greater risk of developing TB compared to HIV-uninfected subjects and have lower TB treatment success rates. In 2014, among the 9.6 million incident cases of TB reported worldwide, 12% occurred in PLHIV and 0.4 million deaths from HIV-associated TB were recorded.Mycobacterium tuberculosis is the main etiological agent for TB. For a majority of individuals, the immune response upon infection by M. tuberculosis is sufficient to prevent the development of disease, but insufficient to clear the bacteria. This leads to the persistence of viable M. tuberculosis in diverse cells with no resulting clinical manifestations, an entity known as latent tuberculosis infection (LTBI). The resulting reservoir of M. tuberculosis is vast, and an estimated one third of the world population is concerned. For subjects with LTBI, the life-time risk of reactivation and progression to TB lies between 5 and 10%. However, if co-infected with HIV, the risk is much greater and reaches 10% per year. According to a Cochrane review in 2010, the screening and treatment of LTBI in PLHIV reduces this risk by 30-60%. This prevention strategy is therefore widely recommended. However, the implementation of LTBI screening and treatment into standard HIV-care has been limited. In this work, three different approaches have been used to understand and address this issue, focusing on a low TB-incidence and high-income setting.The first approach was to assess the implementation of LTBI screening in HIV-care across Belgium and identify its barriers as perceived by the caregivers on the field. Raising awareness to this issue was an indirect objective of the study. A multi-choice questionnaire was sent to 55 physicians working in a Belgian AIDS reference center or satellite clinic. A response rate of 62% was obtained. Only 20% of participants performed LTBI screening on all their patients and notable variations in the screening methods used were observed. A large majority of participants were in favor of targeting LTBI screening to HIV-infected patients at highest risk of TB rather than a systematic screening of all PLHIV. These results have been communicated to the Belgian LTBI working group, currently updating the national LTBI screening guidelines. Indeed, targeting screening to those at highest risk of TB is an attractive strategy in low-TB incidence countries and is already recommended in the United Kingdom. However, to date, no score assessing the risk of TB in PLHIV has been validated. Among the barriers to LTBI screening identified by the participants of this first study, the most frequently reported were lack of sensitivity of screening tools, risk associated to polypharmacy and toxicity of treatment. Improving the sensitivity of LTBI screening was the cornerstone of the second approach. The available screening tools for LTBI are the tuberculin skin test (TST) and two Interferon-gamma release assays (IGRAs): the QuantiFERON-TB Gold-IT (QFT-GIT) and the T-SPOT.TB®. All three lack sensitivity in PLHIV. Various strategies to discover superior LTBI screening tools are therefore being explored, including the development of IGRAs in response to alternative M. tuberculosis antigens to those used in the QFT-GIT or T-SPOT.TB®. A potential candidate is the native Heparin-Binding Haemagglutin (nHBHA), a methylated M. tuberculosis protein regarded as a latency-associated antigen. An in-house IGRA based on nHBHA (nHBHA-IGRA) has been shown to be a promising LTBI screening tool both in immunocompetent adults and in hemodialysed patients. The contribution of this nHBHA-IGRA to the detection of M. tuberculosis in PLHIV was therefore investigated. Treatment-naïve HIV-infected subjects were recruited from 4 Brussels-based hospitals. Subjects underwent screening for latent TB using the nHBHA-IGRA in parallel to the classical method consisting of medical history, chest X-ray, TST and QFT-GIT. Prospective clinical and biological follow-up ensued, with repeated testing with nHBHA-IGRA. Among 48 candidates enrolled for screening, 9 were diagnosed with LTBI by combining the TST and QFT-GIT results (3 TST+/QFT-GIT+, 1 TST+/QFT-GIT- and 5 TST-/QFT-GIT+). All 3 TST+/QFT-GIT+ patients, the TST+/QFT-GIT- patient as well an additional 3 subjects screened positive with the nHBHA-IGRA. These 3 additional patients had known M. tuberculosis exposure risks compatible with LTBI. During follow-up (median 14 months) no case of TB was reported and nHBHA-IGRA results remained globally constant. Multiplex analysis confirmed IFN- as the best read-out for the assay. From this study, we concluded that the nHBHA-IGRA appears complementary to the QFT-GIT for the screening of LTBI in PLHIV and the combination of the two tests may increase the sensitivity of screening. A large-scale study is however necessary to determine whether combining nHBHA-IGRA and QFT-GIT offers sufficient sensitivity to dismiss TST, as suggested by our results. In the same study, a group of HIV-infected adults with clinical suspicion of active TB were also recruited and tested with nHBHA-IGRA. Contrary to results in HIV-uninfected subjects, the nHBHA-IGRA could not discriminate between LTBI and active TB in PLHIV. This is an important caveat as HIV-infected subjects may present subclinical TB.A different angle was used for the third approach to the problem of LTBI in PLHIV. Systemic immune activation (SIA) is one of the principal driving forces in the natural course of HIV-infection. Despite long-term viral suppression by combination antiretroviral treatment (cART), a low-level SIA persists and is associated with an early-onset of age-associated disorders such as cardiovascular disease, dementia and osteoporosis. Causes of SIA in PLHIV are multiple and certain chronic infections appear to be implicated. A recent study in South Africa found that LTBI in PLHIV was associated with an increase in circulating activated CD8+ T-cells. If LTBI should contribute to the persistence of SIA, its screening and treatment could have an additional benefit on the clinical outcome of PLHIV. To investigate this theory, the expression of T-cell activation markers (CD38 and HLADR) as well as the level of plasmatic markers of immune activation (IL-6, sCD14, D-Dimers) were compared between subjects presenting active TB, subjects with LTBI and M. tuberculosis-free persons, with and without HIV-infection. In accordance with previous studies, active TB was associated with higher levels of SIA biomarkers in both HIV-infected and -uninfected groups. Among the HIV-uninfected subjects, no significant difference in biomarker level was found between those presenting LTBI and those with no evidence of M. tuberculosis. The effect of LTBI on activation biomarkers in the HIV-infected groups remained inconclusive because of the small number of individuals in the HIV+/LTBI group. Further investigation is therefore warranted. Interestingly, it was found that plasmatic markers may have a greater sensitivity for the detection of M. tuberculosis-associated SIA than the T-cell activation markers, an important result for future studies.Overall, LTBI in PLHIV is a challenging topic, in particular because of the lack of a gold-standard for the diagnosis of LTBI. Despite suboptimal tools, the evident clinical impact of LTBI screening and treatment in PLHIV on TB incidence justifies its implementation in standard HIV-care. In low TB-incidence countries, who, when and how to screen for LTBI in PLHIV remains unclear. This work offers an overview on the subject with particular focus on possible measures for improvement in the field. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Master of Science / Department of Family Studies and Human Services / Karen S. Myers-Bowman / Today the HIV/AIDS epidemic is one of the many crises families may face. Many people have died of the disease while others are still living with it. At the end of 2003, an estimated 1,039,000 to 1,185,000 persons in the United States were living with HIV/AIDS, with 24-27% undiagnosed and unaware of their HIV infection. The Centers for Disease Control (CDC) estimates that approximately 40,000 persons become infected with HIV each year (CDC, 2007). Stigmatization and discrimination related to HIV/AIDS is one of the many challenges that individuals and families affected by the disease face. They are unable to get employment, are denied health care, cannot access services in their communities and sometimes lose respect and power as a result of stigma. Stigma and discrimination also have been recognized as one of the main obstacles to HIV/AIDS, testing, prevention and treatment and yet little has been done to combat it. Stigma and discrimination is not only experienced by people living with HIV/AIDS but their family members, close friends, service providers and people that work with them also are stigmatized by association. This report highlights the need for family life educators to expand HIV educational programs to include issues on stigmatization and discrimination. It identifies some of the reasons why people stigmatize, the ways which stigma and discrimination are expressed and the impacts it has on individuals and their family members. Using Bronfenbrenner’s ecological model of human development, this report identifies the need to look at HIV-related stigma and discrimination as a societal problem rather than individual problem, and presents implications for education programs for the general public.

Magister Public Health - MPH / Antiretroviral regimens have side effects that can threaten adherence by patients resulting in evolution of viral resistance due to suboptimal drug levels. Studies have shown that drug adherence of at least 80% can result in viral load suppression. There is no literature on the association between the level of adherence to antiretroviral therapy and the degree of virological suppression in Namibia. The aim of the present study was to determine the therapeutic and virological outcomes in HIV/AIDS patients at 6 and 12 months after initiation of highly-active antiretroviral therapy (HAART) in an urban population in Namibia. The distribution of viral load results showed a low uptake (35%) of virological monitoring at 6 month time point and even lower (12%) at 12 months. A conservative viral load threshold for virological response is required in the Namibian setting. The current adherence level of >80% encourage increased ARV therapy rollout. Poor virological outcome was associated with self-reported adherence. / South Africa

Magister Public Health - MPH / A qualitative descriptive study approach was used to gather the required information. The sample for this study was drawn from an existing group of volunteers who participated in the vaccine trial at Mbeya Medical Research Centre in 2006-2007. A purposive sampling method was used to select respondents because they had had experience of being participants in a HIV vaccine trial. Twenty audio recorded in-depth interviews were conducted. The interviews were conducted at the clinic during their routine follow up visits. An open ended interview guideline was used to guide the discussion to elicit the required information from the respondents. The data was transcribed, translated and then analyzed by both content and thematic approach. Ethical procedures were observed, including getting permission from the local ethical committee in Mbeya region and participants were given an informed consent form to read and sign before starting the interview. / South Africa

Philosophiae Doctor - PhD / There is a growing interest in the dynamics of the co-infection of these two diseases. In this thesis, firstly we focus on studying the effect of a distributed delay representing the incubation period for the malaria parasite in the mosquito vector to possibly reduce the initial transmission and prevalence of malaria. This model can be regarded as a generalization of SEI models (with a class for the latently infected mosquitoes) and SI models with a discrete delay for the incubation period in mosquitoes. We study the possibility of occurrence of backward bifurcation. We then extend these ideas to study a full model of HIV and malaria co-infection. To get further inside into the dynamics of the model, we use the geometric singular perturbation theory to couple the fast and slow models from the full model. Finally, since the governing models are very complex, they cannot be solved analytically and hence we develop and analyze a special class of numerical methods to solve them. / South Africa

Magister Public Health - MPH / Eligibility for antiretroviral therapy (ART) in HIV-infected patients is defined either by a cluster of differentiation antigen 4 (CD4) count of less than 200cells/mm3 or clinical diagnosis of WHO stage III and IV. Therefore, the decision to start ART becomes difficult when CD4 cell count is not available. With limited laboratory infrastructure, the decision to start ART is usually made based on clinical symptoms leading to late commencement of ART. This calls for alternative criteria to see if nail discoloration (ND) correlates with low CD4 count among untreated HIV infected patients. This will serve as a complementary screening tool for identifying asymptomatic ARV naive HIV patients with a CD4 cell count of less than 200cells/mm3 which signifies severe immunosuppression. Study Design and Setting: This was a quantitative cross-sectional descriptive and analytical study involving adult ART naïve HIV infected patients in WHO stage I and II. Systematic sampling was used to select the participants from all adult ART naïve HIV infected patients attending APIN clinic, located at the Jos University Teaching Hospital (JUTH), Jos, Nigeria. Data Collection: Face-to-face interviews, physical examination and relevant laboratory investigations with selected participants were conducted using a questionnaire guide. Questions on socio-demographic characteristics, clinical data, general physical examinations including finger nail examination and photographing with subsequent laboratory investigations including CD4 count and western blot were employed. Data Analysis: Variables were categorized and data analyzed using descriptive statistics including the frequency, percentage frequency; mean and standard deviation of continuous variables. Association between CD4 count of ≤200cells/mm3 and ND was tested using the chisquare test with an alpha level of 0.05. Prevalence of ND, sensitivity, specificity, positive predictive and negative predictive values and accuracy of the screening test of ND was calculated. Results: 394 patients had their fingernails photographed and assessed. It was shown that distal banded and grey nails were the common types of ND seen with a prevalence of 38%. There was an association between CD4 count ≤200cells/mm3 and ND (p<0.0001). CD4 count ≤200cells/mm3 was a risk factor for developing ND (RR=2.3[1.8-3.6]). The association has a sensitivity of 78%, specificity of 55%, positive predictive value of 50%, and negative predictive value of 80% and accuracy of test 63%. Conclusion: With a significant association (p<0.0001) and a sensitivity of 78%, ND can be a useful clinical indicator of immune dysfunction mediated by HIV among patients in WHO stage I or II. ND can either be a clinical sign or a symptom in HIV patients with a CD4 of ≤200cells/mm3 as seen in the study as the specificity and sensitivity of ND compared favourably with other WHO stage III diagnosis. Recommendations: Nail discoloration should complement CD4 count as an additional staging sign to help identify patients likely to benefit from ART especially in resource-limited settings. Finally, all patients with grey or distal banded should be on co-trimoxaxole prophylaxis in line with WHO /national guideline on the use of co-trimoxaxole for all HIV positive patients with a CD4 cell count of ≤350cells/mm3. / South Africa