Thesis (MA)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: The topic of antiretroviral adherence remains a subject of continued importance, as it is associated with positive health outcomes amongst patients attending public healthcare facilities. Available literature on adherence behaviour mainly focuses on the psychological and behavioural barriers, while overlooking the multitude of structural barriers within the patient’s environment affecting the patient’s adherence to antiretroviral treatment and care. The present study provides a unique perspective on adherence behaviour amongst persons living with HIV and receiving antiretroviral treatment, as it identifies important structural barriers to clinical attendance and pill-taking. The sample for this study were selected from patients attending an infectious diseases clinic at a major peri-urban secondary hospital and receiving antiretroviral therapy, nurses and doctors providing health services to patients, and patient advocates providing psychosocial support to patients under the auspices of a local non-governmental organisation. The participants included in this study were selected by means of convenience sampling to participate either in semi structured interviews or focus group discussions. Participants were assured of the confidentiality of the process and their anonymity in both cases. Both semi structured interviews and focus groups were digitally recorded and transcribed after which transcriptions were entered into Atlas.ti for textual analysis. Transcriptions were thematically analysed according to the perceptions of various participants. The main themes that emerged from the present study included individual barriers, poverty-related barriers, institutionrelated barriers, and social and community-related barriers. The results of the present study were triangulated by considering the concurrences and discrepancies between the patients, clinicians and patient advocates on the main, and subthemes. These themes were then discussed according to Bronfenbrenner’s (1972) Ecological Systems Theory, which divided the main themes identified according to the different systems operating within the patient’s environment, i.e. the micro-, exo-, and macrosystem. The microsystem included both individual psychological and behavioural barriers and poverty-related barriers. Institutional barriers were considered within the exosystem of the patient’s ecological environment. And the social and community-related barriers were considered within the macrosystem of the patient’s ecological environment. The significance of this study lies in the identification of adherence behaviour as the product of the patient’s environment through the examination of triangulated data. Future research may include effective ways in which patients can be assisted in developing the necessary skills to cope with their environment and to enhance social support. The development of strategies to support newly-enrolled patients also still needs investigation. / AFRIKAANSE OPSOMMING: Volgehoue antiretrovirale behandeling bly ‘n onderwerp van voortdurende belang omdat dit geassosieer word met positiewe gesondheidsuitkomste onder pasiënte wat van openbare gesondheidsfasiliteite gebruik maak. Beskikbare literatuur oor volhoudings gedrag fokus grootliks op sielkundige en gedragshindernisse, terwyl veelvuldige strukturelehindernisse binne die pasiënt se omgewing steeds misgekyk word. Dié studie bied ‘n unieke perspektief op volhoudingsgedrag onder MIV-positiewe pasiënte wat tans antiretrovirale terapie ontvang, aangesien dit belangrike strukturele hindernisse tot kliniek bywoning en die neem van medikasie identifiseer. Dié steekproef sluit pasiënte in wat tans antiretrovirale terapie by ‘n aansteeklike siektes-kliniek by ‘n peri-stedelike sekondêre hospitaal ontvang. Dit sluit ook dokters en verpleegsters in wat gesondheidsdienste aan dié pasiënte verskaf, en pasiënt- advokate wat psigo-sosiale ondersteuning aan pasiënte verskaf onder die vaandel van ‘n plaaslike nieregerings organisasie. Dié deelnemers is deur middel van gerieflikheidssteekproef geselekteer om aan semi-gestruktureerde onderhoude of fokusgroepbesprekings deel te neem. Deelnemers van albei groepe is van hul anonimiteit en die vertroulikheid van die proses verseker. Beide die semi-gestruktureerde onderhoude en die fokusgroepbesprekings is digitaal opgeneem en transkripsies is daarvan gemaak, waarna die transkripsies in Atlas.ti gelaai is vir tekstuele analise. Transkripsies is tematies geanaliseer volgens die persepsies van die verskeie deelnemers. Die hooftemas wat na vore gekom het, sluit in individuele hindernisse, armoedeverwante hindernisse, institusieverwante hindernisse asook sosiale en gemeenskapsverwante hindernisse. Resultate van dié studie is getrianguleer deur die verskille en ooreenkomste te vind tussen pasiënte, klinici en pasiënt-advokate oor die hoof- en subtemas. Die hooftemas is toe volgens Bronfenbrenner (1972) se Ekologiese Sistemeteorie verdeel in die verskillende sisteme teenwoording in die pasiënt se omgewing, naamlik die mikro-, ekso-, en makrosisteem. Die mikrosisteem het individuele sielkundige en gedragshindernisse asook die armoedeverwante hindernisse ingesluit. Institusieverwante hindernisse is binne die eksosisteem van die pasiënt se ekologiese omgewing beskou en sosiale en gemeenskapsverwante hindernisse is beskou binne die makrosisteem van die pasiënt se ekologiese omgewing. Die belang van dié studie lê in die identifisering van volhoudingsgedrag as produk van die pasiënt se omgewing, soos beskou deur die Ekologiese Sistemeteorie. Toekomstige navorsing kan fokus op effektiewe maniere waarop pasiënte bygestaan kan word om die nodige vaardighede te ontwikkel om hul omgewing beter te kan hanteer en beskikbare sosiale ondersteuning te kan verbeter. Die ontwikkeling van strategieë om nuwe pasiënte by te staan, benodig ook verdere navorsing.

The Human immunodeficiency virus (HIV) pandemic has resulted in a heavy global disease burden, and clinically causes Acquired Immuno-Deficiency Syndrome (AIDS). The development of highly active antiretroviral therapy (HAART) has achieved remarkable control of the rapidly evolving HIV. However, HIV remains neither curable nor preventable by vaccine, and in the developing regions worst affected by HIV, HAART remains inaccessible to most patients. Furthermore, the change in both immunology and viral evolution during chronic HIV infection and its relation to AIDS pathogenesis remains unknown. Following the failure of recent HIV vaccines, it is believed that a better understanding of host-pathogen interaction is vital to advance therapeutic (vaccine and drug) design. In this thesis, I have performed an investigation of viral adaptation in response to different selection forces during advanced HIV infection and AIDS. The thesis first examined a case study that reveals the potential role of B cell-mediated neutralising antibody (NAb) in chronic HIV infection through the unexpected effect of B cell depletion agent, anti-CD20 (Rituximab). Here, longitudinal results have shown that viral load (VL), env gene diversity, and NAb sensitive strains increased during B cell and NAb depletion as a result of Rituximab administration, and reversed as B cells recovered. The study provides preliminary evidence to support the idea that NAb may be effective at suppressing HIV. The rest of the thesis focused on the cross-sectional cohort at Bloemfontein, South Africa (n=1491), a resource-limited region affected by the pandemic. Here, we used methods that include molecular and pretherapy drug resistance epidemiology, mathematical modelling, phylogenetically adjusted bioinformatics analysis and in vitro viral replication capacity (VRC) assay to study materials including cohort demography, plasma samples, CD4 cell count, VL, viral genetic sequences and host human leukocyte antigen (HLA) tissue types. Our analysis was further augmented by the additional data kindly contributed by our neighbouring Durban cohort collaborators (n=775), which also includes an IFN! ELISPOT assay that measures cytotoxic T lymphocyte (CTL) responses. Using the HIV pol sequencing data and phylogenetic analysis we confirmed that the local molecular epidemiology is similar to the circulating strains documented in the regional database. However, the pretherapy drug resistance mutation screening results have revealed an unexpected high incidence of drug-induced viral mutants in the AIDS patients with CD4 counts <100 cells/μl. According to mathematical modelling, this finding is attributable to additional sources of antiretroviral therapy exposure, which warrants public health caution. The investigation then focused on studying the changes in HLA class I mediated CTL selection and viral evolution as CD4 counts are reduced in AIDS. Interestingly we have noted evidence that suggest weakening CTL immune selection against gag during AIDS is associated with increased viral fitness (measured by VRC) and reversion of previous immune-escape mutations which conferred high fitness costs. In conclusion, this thesis compared different sources of host and drug mediated HIV selection and its implication for viral evolution. The identification of more bottleneck sites conferring high fitness costs to the selection of escape mutants is expected to be helpful in the design of future therapeutics (via vaccine, drug, immune therapy, or public health strategy). As we have learnt from the principle of combinational ARV, it would be desirable for a vaccine to select HIV at multiple sites of high escape-mutation fitness cost, hence offering protective effect.

Bien que l'infection par le virus de l'immunodéficience humaine (VIH) ne puisse être éradiquée, elle peut être contenue, et les traitements antirétroviraux (ARV) constituent la meilleure option existante pour empêcher de façon durable la réplication virale chez les personnes infectées. Chaque molécule ARV, seule est insuffisante pour juguler l'action du virus. Pour devenir "hautement actives", les thérapies ARV (highly Active Antiretroviral Therapies, HAART) doivent combiner l'action complémentaire de plusieurs molécules qui doivent être consommées ensembles. Si les avancées de la littérature économique existante sur les marchés pharmaceutiques restent pertinentes, de nouvelles considérations doivent venir s'ajouter à l'étude de marché des traitements utilisés pour la prise en charge du VIH. Cette caractéristique composite inhérente aux multithérapies, peut être appréhendée par le concept économique de bien "système". En s'appuyant sur deux projets de recherche menés au Brésil et dans sept pays d'Afrique subsaharienne, cette thèse s'attache à analyser les implications des évolutions du marché pharmaceutique inetrnational non plus au seul niveau de chaque molécule mais également au niveau de la multithérapie dans son ensemble. En participant à la meilleure compréhension des mécanismes qui sous-tendent aux marchés des médicaments ARV à destination des pays du Sud, les leçons issues de ces études empiriques, à la croisée entre droits de propriété intellectuelle, structure de marché, coût et disponibilité des traitements, apportent une contribution aux débats économiques et de santé publique engendrés par l'objectif d'un accès universel aux traitements du VIH. / Although human immunodeficiency virus (HIV) cannot be cured, infection with HIV can be restrained by antiretroviral (ARV) therapy, the best existing option to suppress replication of the virus on a long term basis among treated patients. Action of each individual ARV molecule, by itself, is inadequate to suppress viral replication. To become "highly active", antiretroviral therapies (HAART) have to combine several complementary drugs which have to be consume together. Even if existing economic literature on pharmaceutical markets offers several valuable insights, the analysis of markets in drugs used against HIV infection must take into account the composite structure of treatment. Such specificity, inherent ARV therapy, can be analyzed through the economic concept of "system " goods. The thesis is based on two empirical researches which have been conducted in Brazil and in seven sub-saharan Africa countries with aim to study recent evolutions that occured on the international pharmaceutical market considering both individual molecule and ARV therapy as a whole. Standing at the crossroads between intellectual property rights, market structures, treatment cost and availability, lessons emerging from our researcg contribute to provide a better understanding of mechanisms impacting on ARV markets in Southern Countries as well as economic and public health debates raised by the issue of universal access to HIV treatment.

Introducción: La atención farmacéutica mejora la adherencia del paciente al tratamiento, por lo que es necesario que el farmacéutico cuente con instrumentos para evaluarla y mejorarla mediante su intervención en el seguimiento farmacoterapéutico (SFT). Objetivos: Evaluar el impacto de la intervención farmacéutica en la mejora de la adherencia de los pacientes con virus de la inmunodefi ciencia humana (VIH) y sida, e identifi car los factores que infl uyen en ella y que pueden ser modifi cados por la intervención farmacéutica en el SFT. Métodos: Se realizó SFT durante 23 meses a 52 pacientes mayores de 18 años de edad, con tratamiento antirretroviral durante más de 3 meses, que dieron su consentimiento informado. La adherencia se evaluó con el CEAT-VIH (cuestionario para evaluar la adhesión al tratamiento antirretroviral) al inicio y al fi nal de 6 meses de SFT. Resultados: La puntuación total del CEAT-VIH (p <0,05; intervalo de confi anza del 95%), el cumplimiento del tratamiento (p <0,001) y la percepción del paciente respecto a su enfermedad y tratamiento antirretroviral (p <0,001) incrementaron signifi cativamente su valor. La educación al paciente para incrementar la adherencia al tratamiento (46%) fue la intervención farmacéutica más frecuente. Conclusiones: Se demuestra que la intervención del farmacéutico, mediante el SFT, mejora la adherencia al tratamiento antirretroviral. El farmacéutico mejoró los aspectos de cumplimiento y percepción del paciente sobre su tratamiento y enfermedad. Los farmacéuticos pueden utilizar el CEAT-VIH como instrumento para evaluar la adherencia en la práctica del SFT. / Introduction: Pharmaceutical care improves medication adherence that is why is important that the pharmacist uses instruments to evaluate and improves it through pharmaceutical intervention at pharmaceutical care. Objective: To evaluate the impact of the pharmaceutical intervention in the improvement of the medication adherence of the patients with HIV and AIDS, and to identify the factors that infl uence on medication adherence and which one could be modifi ed by the pharmaceutical intervention during pharmaceutical care. Methods: Pharmacotherapeutic follow-up was realized for 23 months to 52 patients, older than 18 years, with antiretroviral treatment for up to three months, consent informed was obtained from patients. Medication adherence was evaluated with CEAT-HIV (questionnaire to evaluate the adhesion to the antiretroviral treatment) at the beginning and at the end of the study (6 months). Results: The fi nal score from CEAT-HIV (p <0.05; 95% IC), treatment compliance (p <0.001) and patient’s beliefs to the disease and antiretroviral treatment (p <0.001) improved signifi cantly with the pharmaceutical intervention. The more frequent pharmaceutical intervention was education to the patient to increment the adherence to the treatment (46%). Conclusion: These results demonstrate that the pharmacists’ intervention through pharmacotherapeutic follow-up improves the adherence to the antiretroviral treatment. The pharmacist was able to improve aspects of compliance and patient’s beliefs about the treatment and disease. The pharmacist could utilize CEAT-VIH as an instrument to evaluate the adherence in HIV/AIDS patients.

Introdução: Existe crescente interesse em identificar marcadores de risco para eventos cardiovasculares em pacientes com HIV/aids. Atualmente observa-se alteração do perfil epidemiológico desses pacientes, com diminuição da mortalidade por infecção e comorbidades e aumento por eventos cardiovasculares. A elasticidade arterial, principalmente dos pequenos vasos, tem sido investigada como alteração precoce de evento cardiovascular. Objetivo: Avaliar a relação entre elasticidade arterial e outros indicadores de risco cardiovascular como fatores demográficos e socioeconômicos, hábitos de vida, estado nutricional e marcadores inflamatórios. Métodos: Foram selecionados aleatoriamente 132 indivíduos voluntários em tratamento regular com antirretrovirais em ambulatório especializado em HIV/aids, com idade entre 19 e 59 de ambos os sexos. A elasticidade arterial dos grandes vasos (LAEI) e pequenos vasos (SAEI) foi investigada pelo equipamento HDI/ PulseWaveTM CR-2000 Cardio Vascular Profiling System®. Foram determinados colesterol total e frações, triglicérides, proteína C-reativa, fibrinogênio, medidas antropométricas e de avaliação de composição corporal, fumo, consumo de bebidas alcoólicas, uso de drogas, prática de atividade física, além de avaliação de fatores demográficos e socioeconômicos e imunológicos (carga viral, T-CD4, T-CD8). Para investigar a associação entre LAEI e SAEI e outros fatores de risco cardiovascular utilizou-se análise de regressão linear múltipla. Resultados: Em relação à elasticidade dos grandes e pequenos vasos, 71,97 por cento e 32,58 por cento , respectivamente, dos participantes foram classificados com elasticidade normal. Observou-se associação positiva entre LAEI e peso (p<0,001) e associações negativas entre LAEI e prega cutânea subescapular (p<0,001) e linfócitos T-CD4 (p<0,02). Verificou-se associação negativa de LAEI com sexo (p<0,02), mostrando que o sexo feminino está relacionado com menor elasticidade. Houve associação positiva entre SAEI e peso (p<0,001) e associações negativas entre SAEI e prega cutânea subescapular (p<0,001), idade (p<0,01) e linfócitos totais (p<0.01). Conclusão: As alterações de elasticidade arterial em pacientes HIV/aids apresentaram relação com outros fatores de risco cardiovascular. SAEI mostrou-se diminuído na maioria dos participantes, sendo uma alteração que pode identificar a disfunção endotelial antes que a doença se torne clinicamente aparente. A monitoração constante da elasticidade arterial através de método não invasivo pode se tornar uma importante ferramenta na predição e prevenção de eventos cardiovasculares em pacientes HIV/aids / Introduction: There is a growing interest in identifying markers of risk for cardiovascular events in patients with HIV / AIDS. Currently there is a change in the epidemiological profile of patients with reduced mortality from infections and comorbidities and increased cardiovascular events. The arterial elasticity, mainly of small vessels, has been investigated as early alteration of cardiovascular events. Objective: To evaluate the relationship between arterial elasticity and other cardiovascular risk factors such as demographic and socioeconomic factors, lifestyle habits, nutritional status and inflammatory markers. Methods: We randomly selected 132 individuals volunteers, ages between 19 and 59, of both sexes, regularly treated with antiretrovirals in specialized clinics on HIV / AIDS. Arterial elasticity of the large (LAEI) and small (SAEI) vessels were investigated by the equipment HDI/ PulseWaveTM CR-2000 Cardio Vascular Profiling System®. We determined total cholesterol, HDL, triglycerides, C-reactive protein, fibrinogen, and anthropometric assessment of body composition, smoking, alcohol consumption, drug use, physical activity, and evaluation of demographic, socio-economic and immunological (viral load, T-CD4, T-CD8) factors. The association between LAEI and SAEI and other cardiovascular risk factors were assessed by multiple linear regression. Results: Regarding the elasticity of large and small vessels, 71.97 per cent and 32.58 per cent , respectively, of the participants were classified as having normal elasticity. We observed a positive association between LAEI and weight (p <0.001) and negative associations between LAEI and subscapular skinfold (p <0.001) and CD4 counts (p <0.02). There was a negative association of LAEI with gender (p <0.02), showing that female gender is associated with lower elasticity. There was a positive association between SAEI and weight (p <0.001) and negative associations between SAEI and subscapular skinfold (p <0.001), age (p <0.01) and total lymphocytes (p <0.01). Conclusion: Changes in arterial elasticity in patients with HIV / AIDS correlate with other cardiovascular risk factors. SAEI was altered in most participants, a change that can identify endothelial dysfunction before the disease becomes clinically apparent. The constant monitoring of arterial elasticity through noninvasive method may become an important tool in the prediction and prevention of cardiovascular events in HIV / aids patients

Redução da densidade mineral óssea tem sido descrita como uma complicação clínica entre as pessoas vivendo com HIV/AIDS. Entretanto não há dados descrevendo essa alteração entre os pacientes brasileiros. Nosso objetivo foi investigar a prevalência de baixa densidade mineral óssea entre pessoas vivendo com HIV/AIDS na cidade de São Paulo. Nós estudamos108 pacientes infectados pelo HIV (78 homens e 30 mulheres). Foram utilizados neste estudo dados secundários. Os dados foram originalmente coletados com o objetivo de acompanhamento de rotina dos pacientes na clínica e para este estudo estes dados foram coletados dos prontuários médicos. Todos os pacientes foram submetidos ao exame de densitometria óssea, que é uma técnica radiológica que mensura a densidade mineral óssea. Os pacientes foram classificados como tendo baixa densidade mineral óssea de acordo com a classificação da organização mundial da saúde que define osteopenia quando o T-score a partir de -1,1 e osteoporose quando T-score abaixo de -2,5 quando se tratava de homens e mulheres com idade acima de 50 anos. Quando homens e mulheres tinham idade até 50 anos, utilizamos a classificação da ISCO, neste grupo baixa densidade mineral óssea foi definida quando os pacientes apresentavam um Z-score abaixo de -2. Entretanto para este estudo ambas as classificações foram definidas como baixa densidade mineral óssea. A mediana de idade, tempo de infecção pelo HIV a partir da data do diagnóstico, tempo sob terapia antiretroviral, número de células linfócitos TCD4+ no momento da avaliação e Nadir foram similares entre homens e mulheres. A mediana de idade foi de 43 anos (intervalo interquartílico [li] 43-48 anos) e mediana de tempo de infecção pelo HIV foi de 3,66 anos (intervalo interquartílico [li] 1,72- 10,91 anos). Os pacientes tinham adquirido o HIV principalmente pela via sexual (homens que fazem sexo com home 46% e 50% eram heterossexuais). A mediana de células linfócitos TCD4+ foi de 399céls/mm 3(intervalo interquartílico [li] 275 - 566,5). Vinte e cinco pacientes foram classificados como tendo baixa DMO (23,15%). Não houve associação estatisticamente significante entre sexo, IMC, nadir e baixa DMO. Os fatores de risco associados à baixa DMO foram células linfócitos TCD4+ <350 céls/mm3 idade acima de 502 anos e tabagismo (p=0,003; p= 0,001; p=0,002) respectivamente. Quando avaliamos HAART VS baixa DMO encontramos 14,28% de baixa DMO entre os que usavam HAART e 26,25% entre os que não usavam e essa diferença não foi estatisticamente significante. Uma limitação de nosso estudo foi o tamanho de nossa amostra, coortes maiores talvez encontrem resultados diferentes. Contudo, nossos achados fortemente sugerem que a identificação de fatores de risco para baixa DMO e que são modificáveis são um importante componente no manejo desses pacientes para prevenção da baixa DMO e do risco de fratura atribuído a essa alteração. Portanto nossos resultados sugerem que esforços no sentido de encorajamento de cessação do tabagismo devem ser realizados e considerados um importante componente de qualquer programa de saúde dos indivíduos com HIV/AIDS. Identificar fatores de risco modificáveis pode contribuir para formulação de melhores políticas de saúde. / Reductions in bone mineral density (BMD) has been reported as a complication among people living with HIV/AIDS. However, no data describing this complication in Brazilian HIV infected patients have been reported . To investigate the prevalence of osteopenia/osteoporosi s among HIV-infected persons living in Sao Paulo City. We studied 108 HIV-infected patients (78 men and 30 women). We abstracted data from medical charts. All subjects enrolled in this study were submitted to Bone densitometry or dual-X-ray absorptiometry , a radiological technique using low-intensity X-ray . lt measures the bone mineral density content. lf the patients were postmenopausal woman and men aged 50 or above , they were classified as having low bone mineral dens ity when a T-score < -1 at the lumbar spine or femoral neck was detected. lf it was from -1,.1 to -2,5 osteopenia was defined and if it was < -2.5 osteoporosis was defined , using the WHO organization definition. Premenopausal woman and men younger than 50years are classified according to the current ISCO criteria, using Z-score <- 2,0 SD at the lumbar spine or femoral neck. For the propose of this study we combined both classification as Low Bone Mienral Density. Median age was 43 years (IQR 43 - 48 years). and the emdian time since HIV diagnosis was 3,66 years (IQR 1.72 - 10.91). Patients had acquired HIV primarily sexually (men who hasve sex with men 46%, heterosexual 50%). Plasma virai load was undetectable in 53 patients (40.09%) The CD4 T cell count was 399 cells/µ (IQR 275 - 566.5). Twenty-five patients (23.15%) had LBMD. There was no statiscally significant amng gender , body mass índex, nadir and LBMD. The risk factores associetaed were related to having CD4 T cells count <350 mm3 , being older than 50 years and being smoker (p=0.003; p= 0.001; p= 0.002) respectively. Low Bone Mineral Density was encountred 14.28% of patients with HAART, and in 26.25% with no haart. There, HAART was not statistically associated with LBMD. Our study was limited by its small sample. Larger cohort may have different results. Nonetheless, ou finding are compelling and suggesting that addressing modifiable risk factors for low bone mineral density and fragility fractures is an important component of both apporachs. Therefore ou data also suggest that efforts should be directed towards appropriate enouragment of lifestyle change alterations . Specifically , smoking cessation should be a major component of any health program within the HIV/AIDS population. Assessing such risk factors can contribute to the formulation of health policies to address this issue.

Introdução: Atualmente observa-se aumento das complicações cardiovasculares, como alterações no perfil lipídico e oxidativo, em indivíduos com HIV/AIDS, devido à própria infecção, bem como aos diferentes componentes da terapia antirretroviral (TARV). Vários estudos, em outras populações, mostram que os flavonóides presentes no cacau (Theobroma cacao) e erva mate (Ilex paraguariensis) podem melhorar a função cardiovascular devido às suas propriedades antioxidantes e hipolipemiantes. Objetivo: Avaliar o efeito da ingestão de chocolate e erva mate no perfil lipídico e oxidativo de indivíduos com HIV/AIDS em TARV. Metodologia: Ensaio clínico do tipo cross-over, aleatorizado, cego e controlado com placebo envolvendo 89 voluntários, de 28-59 anos de idade, em tratamento regular com TARV por, no mínimo, seis meses e com carga viral <500 cópias/mL. Os voluntários consumiram 65g de chocolate em barra (chocolate preto contendo 36g de cacau e placebo) e 3g de chá (erva mate solúvel e placebo) por 15 dias cada, seguido por 15 dias de washout entre cada período de suplementação. Foram avaliadas as seguintes características: perfil demográfico e socio-econômico, variáveis antropométricas, imunológicas, prática de atividade física, perfil lipídico (colesterol total, LDL-c, HDL-c, não HDL-c, triacilgliceróis e índices de Castelli I e II), e oxidação lipídica (LDL eletronegativa e substâncias reativas ao ácido tiobarbitúrico-TBARS). As análises estatísticas do cross-over foram realizadas através de análises de variância (ANOVA) utilizando o procedimento pkcross no software Stata versão 11.0. Também se realizou teste t de Student pareado entre os parâmetros no baseline e após consumo dos suplementos de interesse (chocolate preto e erva mate). Considerou-se significante p<0,05. Resultados: Os pacientes eram na maioria do sexo masculino (62,9 por cento), com média de idade de 44,6 (±7,1) anos. Observou-se média de 13,2 (±4,8) anos de diagnóstico de HIV/AIDS, com 10,6 (±5,1) anos de uso de TARV. Não houve diferença significativa comparando as médias das variáveis do perfil lipídico e oxidativo entre as diferentes suplementações (chocolate preto, erva mate e placebos) por ANOVA. Entretanto, na comparação entre as variáveis no baseline e após consumo de chocolate preto, pelo teste t de Student pareado, observou-se aumento de colesterol total (p=0,005), HDL-c (p=0,019) e LDL-c (p=0,002). Conclusão: Este é o primeiro estudo clínico que avaliou o efeito da ingestão de chocolate (cacau) e chá mate (erva mate) no perfil lipídico e oxidativo de indivíduos com HIV/AIDS em TARV. No presente estudo, o consumo tanto do cacau quanto da erva mate por 15 dias cada, não foi suficiente para melhorar o perfil lipídico e oxidativo destes indivíduos, apesar do aumento de HDL-c observado após o consumo do chocolate preto. Tal resultado neste grupo de indivíduos pode ser devido ao seu metabolismo diferenciado, o qual sofre alterações não apenas pela própria infecção, mas também pela TARV, a quantidade e biodisponibilidade dos flavonóides nos suplementos e ao tempo de intervenção / Introduction: Nowadays there is an increase of cardiovascular complications, such as changes on the lipid and oxidative profile of individuals with HIV/AIDS due to the infection itself, as well as to the different components of the antiretroviral therapy (ART). Several studies in other populations, show that flavonoids in cocoa (Theobroma cacao) and yerba mate (Ilex paraguariensis) may improve cardiovascular function due to its antioxidant and lipid lowering. Objective: To evaluate the effect of chocolate intake and yerba mate on the lipid and oxidative profile of individuals with HIV/AIDS on ART. Methodology: Randomized, placebocontrolled, blinded cross-over trial involving 89 volunteers ages 28-59 years, in ART for at least six months and with viral load <500 copies/mL. The volunteers consumed 65g chocolate bar (36g dark chocolate containing cocoa or placebo) and 3g of tea (yerba mate soluble and placebo) for 15 days each, followed by 15 days washout period before the subsequent treatment. The following characteristics were evaluated: demographic and socio-economic, anthropometric, immunologic, physical activity, lipid profile (total cholesterol, LDL-c, HDL-c, non-HDL-c, triglycerides and Castelli I and II indices), and lipid oxidation profile (electronegative LDL and thiobarbituric acid reactive substances- TBARS). Statistical analyzes were performed by the cross-over analysis of variance (ANOVA) using the procedure pkcross in Stata version 11.0. The paired Students t-test was also utilized. A p value <0.05 was considered significant. Results: Patients were mostly male (62.92 per cent) with a mean age of 44.6 (± 7.1) years. The mean time of HIV/AIDS diagnosis was 13.2 (± 4.8) years, with 10.6 (± 5.1) years of ART. There was no statistically significant difference comparing the lipid profile and lipid oxidation profile of the individuals under the different supplementations (dark chocolate, yerba mate, and placebo) by ANOVA. However, comparing the variables in the baseline period and after consumption of dark chocolate by the paired Students t-test, there were increases in total cholesterol (p=0.005), HDL-c (p=0.019) and LDL-c (p=0.002). Conclusion: This is the first clinical study that evaluated the effect of chocolate (cocoa) and mate tea (yerba mate) consumption on lipid and oxidative profile of individuals with HIV/AIDS on ART. In the present study, daily consumption of neither cocoa nor yerba mate for 15 days was sufficient to improve lipid and oxidative profile of these individuals, despite the increase in HDL-c observed after consumption of dark chocolate. Such an outcome in this group of individuals can be distinguished due to its metabolism, which is altered not only by the infection itself, but also by the ART, the amount and bioavailability of flavonoids in supplements and timing of intervention

Introdução - Estudos mostram maior ocorrência de complicações cardiovasculares na população HIV/aids. Alguns estudos envolvendo animais e indivíduos saudáveis ou com outras doenças observaram benefícios no consumo de chocolate e erva mate na função endotelial e vasodilatação. Objetivo Avaliar o efeito da ingestão de chocolate e erva mate na elasticidade arterial de indivíduos com HIV/aids em terapia antirretroviral. Métodos Ensaio clínico cruzado, aleatorizado e duplo-cego, envolvendo 89 indivíduos com HIV/aids entre 19 e 59 anos, em tratamento regular com antirretrovirais por no mínimo 6 meses, e carga plasmática do HIV <500 cópias/ml. Os indivíduos receberam suplementação diária com aproximadamente 65g de chocolate amargo, 3g de erva mate ou respectivos placebos por 15 dias, com washout de igual tempo entre as intervenções. A aferição da elasticidade arterial foi realizada por análise do formato da onda de pulso com o equipamento HDI/PulseWaveTM CR-2000®. Também foram avaliados: composição corporal, glicemia, perfil lipídico, proteína C-reativa e concentração plasmática de espécies reativas ao ácido tiobarbitúrico (TBARS). As respostas entre tratamentos foram avaliadas por ANOVA e por teste t de Student pelo Stata® 11.0, considerando-se p< 0,005. Resultados A população foi composta principalmente por homens (62,9 por cento) caucasianos (46,1 por cento) com idade média de 44,6 ± 7,1 anos. O tempo médio de diagnóstico de HIV/aids foi de 13,2 ± 4,8 anos com 10,6 ± 5,1 anos de terapia antirretroviral. Não foram encontradas diferenças significantes na elasticidade arterial dos pequenos e grandes vasos após as suplementações. Conclusão Este é o primeiro estudo a avaliar o efeito da ingestão de erva mate e chocolate na elasticidade arterial de indivíduos com HIV/aids. Apesar das evidências positivas desses alimentos na saúde cardiovascular de animais e indivíduos com outras doenças, os mesmos efeitos não foram observados neste estudo. Provavelmente o tempo de suplementação, a biodisponibilidade das substâncias bioativas e o metabolismo alterado desses indivíduos interferiram nos resultados obtidos, sugerindo a necessidade de melhor investigação desses fatores / Introduction There has been an increase on cardiovascular diseases occurrence in the HIV/aids population. Some studies involving animals and healthy individuals or individuals with other pathologies have shown benefits on endothelial function and vasodilation under use of chocolate and yerba maté. Objective To evaluate the effect of chocolate and yerba maté intake on HIV/aids patient´s arterial elasticity. Methods Double-blind crossover trial including 89 HIV/aids patients, 19 to 59 years of age, on antiretroviral therapy for at least six months, and with viral load <500copies/ml. The individuals consumed daily approximately 65g of dark chocolate, 3g of yerba maté or placebo during 15 days, followed by a 15-day washout period after each intervention. Arterial elasticity was measured using the HDI/PulseWaveTM CR-2000 CardioVascular Profiling System®, which provides a pulse wave contour analysis. Body composition, glicemic index, lipid profile, C-reactive protein and thiobarbituric acid reactive substances (TBARS) were also assessed. The crossover analysis was performed using analysis of variance (ANOVA) on Stata®. The paired Students t-test was also applied. A p value <0.05 was considered significant. Results Most of the individuals were men (62.9 per cent), caucasian (46.1 per cent) aging 44.6 ± 7.1 years. The mean time of HIV/aids diagnosis was 13.2 ± 4.8 years, with 10.6 ± 5.1 years of antiretroviral therapy. There were no significant alterations on elasticity of either large or small arteries after chocolate and yerba maté intake. Conclusion This is the first research to evaluate the effect of chocolate and yerba maté intake on HIV/aids patient´s arterial elasticity. Despite of the positive evidence of these foods on cardiovascular health of animals and populations with other pathologies, the same effects were not observed in this study. Most probably the time of intervention, the bioavailability of the bioactive substances and the altered metabolism of this individuals interfered on the results, which indicates the need for further investigation

Background: The burden of cardiometabolic disease (CMD) is rising in sub-Saharan Africa (SSA). However, there are limited population-based prevalence estimates of CMD risk factors to inform public health initiatives for the prevention and management of CMDs in these populations. This thesis aims to contribute to this evidence gap by assessing the prevalence and distribution of established and emerging CMD risk factors, associations between risk factors, and tools for their identification, in a South African population. Methods: The Durban Diabetes Study (DDS), a population-based cross-sectional survey of CMD risk factors, was designed and data were collected on 1204 participants from the eThekwini Municipality, South Africa. Key findings: In this urban South African population, the prevalence of most CMD risk factors was high, and varied across demographic and socioeconomic groups. The prevalence of smoking and alcohol consumption was higher in men, whilst the prevalence of obesity, hypertension, dyslipidaemia, and hyperglycaemia was higher in women. Wealth was associated with obesity and hypercholesterolemia, whilst education level and employment status were associated with smoking, physical activity and diabetes. Despite several potential advantages, the use of glycated haemoglobin (HbA1c) for diagnosis of diabetes is not established in SSA. Using plasma glucose measures as the reference, HbA1c ≥6.5% detected diabetes with high sensitivity and specificity. Furthermore, the association of anaemia, HIV, and antiretroviral therapy (ART) with HbA1c was modest and no statistically significant differences in the prevalence of diabetes were found in those with anaemia or HIV based on plasma glucose and HbA1c measurements. This is the first evidence for the utility of HbA1c for the diagnosis of diabetes in a black SSA population. There is emerging evidence for the association of HIV and ART with CMD risk factors. In the DDS, the prevalence of HIV was high (43.5%) and untreated HIV was associated with low high-density lipoprotein cholesterol, whilst ART-treated HIV was associated with high triglycerides. Finally, 30.8% of participants were at high risk of CMD based on metabolic syndrome, but only 7.9% had high 10-year cardiovascular disease risk based on the Framingham risk score. Conclusion: This thesis has added to the evidence base on CMD risk factors in South Africa. These findings highlight the need for longitudinal studies to investigate the aetiology of CMDs and robustly assess the utility of tools to identify risk of CMD in SSA populations.

Made available in DSpace on 2016-04-29T14:16:27Z (GMT). No. of bitstreams: 1 Regiane Aparecida de Oliveira Peixoto.pdf: 2772682 bytes, checksum: b798b01d15b50cc6fe5774149c7f6450 (MD5) Previous issue date: 2013-10-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This dissertation focuses the analysis of everyday people who make use of Antiretroviral Therapy for the control of HIV infection. This treatment model was a milestone, allowing infected people to live without opportunistic infections, as well as dramatically reduced AIDS cases and deaths. Brazil s AIDS policy is a model in implementing the principles of the Unified Health System (SUS), especially in the universality of care and social participation for decision making. The goal of the study is to understand how people who undergo this treatment are living, especially their friends, family, work and affective-sexual relationship, considering the difficulties related to prejudice and treatment facilities, such as access to specialized services for HIV/AIDS. The objectives were to reveal the daily life of people living with HIV/AIDS in the use of Antiretroviral Therapy provided by SUS, identifying the different ways of understanding the HIV/AIDS during the treatment process; grasp the implications the difficulties and possible facilities of the HIV/AIDS condition on the lives of people; analyze experiences of discrimination after diagnosis. This is a descriptive, qualitative study, for which elaboration were performed literature and documental research, to determine the major innovation in the arena of HIV/AIDS discussion. The research was conducted with people living with HIV/AIDS in the use of Antiretroviral Therapy, resident of the São Paulo districts of Campo Limpo and M boi Mirim, assisted by the Jardim Mitsutani Specialized Care Service for STD/AIDS, in São Paulo Municipality. Semi-structured interviews and content analysis were conducted based on four axes: reactions to the diagnosis; living with HIV; social relations; treatment for HIV/AIDS. Results show that people living with HIV/AIDS are undergoing major changes in everyday life after the diagnosis, and diverse ways of dealing with the treatment and the meaning attributed to HIV. There is a set of demands linked to living conditions that emerge during treatment and should be considered in the actions affecting these people. The conclusion is that there is a need for constant attention and study on the demands of people living with HIV/AIDS, considering that, during treatment with Antiretroviral Therapy, new demands emerge and have a direct influence on treatment adherence, asking for collective strategies with specialized services for HIV/AIDS / A presente dissertação tem como objeto a análise do cotidiano das pessoas que fazem uso da Terapia Antirretroviral para o controle da infecção do HIV. Esse modelo de tratamento foi um marco, possibilitando às pessoas infectadas viver sem doenças oportunistas, bem como reduziu drasticamente os casos de aids e óbitos. No Brasil, a política de aids é um modelo na concretização dos princípios do Sistema Único de Saúde (SUS), especialmente na universalidade dos atendimentos e na participação social para a tomada de decisões. O foco do estudo é a compreensão de como as pessoas que realizam esse tratamento estão vivendo, especialmente na relação com amigos, família, trabalho e vida afetivo-sexual, considerando-se as dificuldades relacionadas ao preconceito e as facilidades no tratamento, como o acesso aos serviços especializados para HIV/aids. Os objetivos foram revelar o cotidiano de quem vive com HIV/Aids, em uso da Terapia Antirretroviral disponibilizada pelo SUS; identificar as diversas formas de compreender o HIV/aids durante o processo de tratamento; apreender quais as implicações do HIV/aids na vida das pessoas, as dificuldades e suas possíveis facilidades; analisar possíveis experiências de discriminação após o diagnóstico. Tratase de um estudo descritivo, qualitativo, para cuja elaboração foram realizadas pesquisas bibliográfica e documental, visando conhecer as principais inovações na arena do debate sobre o HIV/aids. A pesquisa foi realizada com pessoas que vivem com HIV/aids, em uso da Terapia Antirretroviral, moradoras dos distritos paulistanos de Campo Limpo e M boi Mirim, assistidas pelo Serviço de Assistência Especializada em DST/Aids Jardim Mitsutani, no município de São Paulo. Foram realizadas entrevistas semiestruturadas e análise de conteúdo a partir de quatro eixos: as reações ao diagnóstico; a vida com HIV; as relações sociais; o tratamento para o HIV/aids. Os resultados obtidos mostram que as pessoas que vivem com HIV/aids passam por grandes mudanças na vida cotidiana após o diagnóstico, sendo diversificadas as formas de lidar com o tratamento e com o sentido atribuído ao HIV. Há um conjunto de demandas, vinculadas às condições de vida, que emergem durante o tratamento e devem ser consideradas nas ações junto a essas pessoas. Conclui-se que há necessidade de constante atenção e estudo das demandas das pessoas que vivem com HIV/aids, considerando-se que, no tratamento com a Terapia Antirretroviral, novas demandas emergem e têm influencia direta na adesão ao tratamento, sendo necessárias estratégias coletivas junto aos serviços especializados em HIV/aids