Introdução As deficiências de vitaminas, verificadas em indivíduos com HIV/Aids em terapia antirretroviral de alta potência (HAART) têm sido associadas à piora do curso clínico da doença e maior risco de mortalidade. Objetivo Mostrar a distribuição das concentrações séricas de vitaminas A e E, e beta-caroteno em adultos com infecção pelo HIV/Aids e estudar a associação de suas concentrações, segundo diferentes esquemas de HAART. Métodos Foram selecionados 182 adultos de 20 a 59 anos de idade, de ambos os sexos, com HIV/Aids em HAART estável por no mínimo 6 meses, e com níveis de linfócitos T-CD4+ 200 células/mm3. Os indivíduos foram divididos em três grupos por esquema de HAART utilizado: inibidores de transcriptase reversa análogos de nucleosídeo (ITRN) associados a inibidores de transcriptase reversa não análogos de nucleosídeo (ITRNN); ITRN associada a inibidores de protease (IP); ITRN associadas a outras classes (inibidores de fusão, inibidores de integrase, inibidores de entrada e IP associada a essas medicações). A determinação dos micronutrientes foi realizada por cromatografia líquida de alta eficiência. Foram verificadas variáveis sócio-demográficas e econômicas, estilo de vida, história da doença, uso de medicações e variáveis antropométricas e laboratoriais. Para medir os efeitos das variáveis explanatórias (esquemas de tratamento, tempo de uso e adesão ao último esquema) sobre cada variável resposta (retinol, alfa-tocoferol e beta-caroteno), foram realizadas análises de regressão linear múltipla. Sexo, idade, escolaridade, tabagismo, prática de atividade física, tempo de infecção por HIV, presença de comorbidades, relação cintura-quadril e níveis de linfócitos T-CD4+ e colesterol foram usadas como variáveis de controle. Resultados Foram encontradas concentrações deficientes e baixas de vitaminas A (<0,70Nmol/L) e E (16,2Nmol/L), e beta-caroteno (<0,13Nmol/L) em 3,83 por cento, 18,68 por cento e 23,62 por cento dos indivíduos, respectivamente. Menores concentrações médias de vitamina E foram observadas em indivíduos em uso de ITRN associado a classes mais recentes de antirretrovirais (p= 0,037). Indivíduos com maiores índices de relação cintura-quadril apresentaram maiores concentrações de retinol (p=0,012) e menores concentrações de beta-caroteno (p=0,036). Foram também observadas associações positivas, pequenas e estatisticamente significantes entre as concentrações médias de retinol, alfatocoferol e beta-caroteno com os níveis de colesterol. Conclusão Os resultados sugerem que as alterações nas concentrações de vitamina A e E, e beta-caroteno podem estar relacionadas a múltiplos fatores, incluindo os esquemas de terapia antirretroviral / Introduction Deficiency of vitamins found in individuals with HIV/AIDS on highly active antiretroviral therapy (HAART) has been associated with an increased risk of disease progression and mortality. Objective To show the distribution of serum concentrations of vitamins A and E and beta-carotene in adults with HIV/AIDS, and to study the association of their concentrations, according to different regimens of HAART. Methods We selected 182 men and women aged 20-59 years with HIV/AIDS on stable HAART for at least six months and with levels of CD4+ T-lymphocytes 200 cells/mm3. Individuals were divided into three groups according to the HAART regimen used: nucleoside reverse transcriptase inhibitors (NRTI) combined with nonnucleoside reverse transcriptase inhibitors (NNRTI); NRTI combined with protease inhibitors (PI); NRTI combined with other classes (fusion inhibitors, integrase inhibitors, entry inhibitors, and PI associated with these medications). Determinations of vitamins A and E and beta-carotene were performed by high-performance liquid chromatography. Socio-demographic and economic variables, lifestyle, disease history, medication use, and anthropometric and laboratory variables were assessed. Multiple regression analyses were used to measure the effects of the explanatory variables (treatment regimens, duration and adherence to the last treatment regimen) on each response variable (retinol, alpha-tocopherol and beta-carotene). Sex, age, education, smoking, physical activity, duration of HIV infection, comorbidity, waist-to-hip ratio and levels of CD4+ T-lymphocytes and cholesterol were used as control variables. Results Deficient and low concentrations of vitamin A (<0,70Nmol/L) and E (16,2Nmol/L), and betacarotene (<0,13Nmol/L) were 3,83 per cent, 18,68 per cent and 23,62 per cent, respectively. Lower concentrations of vitamin E (p= 0,037) were observed in individuals using NRTI combined with the most recent classes of antiretrovirals. Individuals who had higher measurements of waist-to-hip ratio presented higher concentrations of retinol (p= 0,012) and lower concentrations of betacarotene (p=0,036). We also observed positive small statistically significant associations between mean concentrations of retinol, alpha-tocopherol and beta-carotene with cholesterol levels. Conclusion The results suggest that changes in the concentrations of vitamins A and E and beta-carotene may be related to multiple different factors, including antiretroviral therapy regimens

Objetivo: O objetivo principal do estudo foi avaliar os fatores associados à qualidade da dieta em adultos vivendo com HIV/Aids em terapia antirretroviral de alta atividade (TARV) no município de São Paulo. Secundariamente, objetivou-se verificar a validade e confiabilidade do uso de medidas referidas de peso e estatura nesta população. Metodologia: Estudo transversal com 508 pessoas vivendo com HIV/Aids (PVHA) de ambos os sexos, com idade entre 20 a 59 anos e que estivessem em uso de TARV há pelo menos três meses, em acompanhamento na Rede Municipal Especializada em DST/Aids de São Paulo. Foram desenvolvidos dois eixos de investigação: (1) estudo sobre a avaliação da validade e confiabilidade do uso de medidas referidas de peso e estatura entre adultos vivendo com HIV/Aids; (2) estudo sobre a avaliação dos fatores associados à qualidade global da dieta de PVHA. Para o estudo da validade, foram realizados cálculos de sensibilidade e especificidade da classificação do estado nutricional baseada nos valores referidos e aferidos de peso e estatura. Para a identificação de erros e padrões sistemáticos de diferenciação entre essas mesmas medidas utilizou-se a representação gráfica de Bland-Altman e para a verificação da confiabilidade foi utilizado o coeficiente de correlação intraclasse. Por fim, foram feitas análises de regressão linear com o intuito de gerar equações que predissessem os verdadeiros valores de peso e estatura a partir dos valores referidos. O indicador de qualidade da dieta estudado foi o Índice de Qualidade da Dieta (IQD) adaptado para a população estudada. O consumo alimentar foi colhido com o uso do Recordatório Alimentar de 24 horas. A fim de serem avaliados os fatores associados à qualidade global da dieta foi utilizada análise de regressão linear múltipla, tendo indicadores sóciodemográficos, clínicos e de estilo de vida como variáveis independentes. Resultados: A maioria dos participantes era do sexo masculino (57,7%), idade média de 41,7 anos (Desvio Padrão DP=7,8) e com escolaridade média de 8,3 anos (DP=3,7). Em relação às medidas antropométricas, as diferenças entre os valores aferidos e referidos de peso foram de -0,96 kg para os homens e de -0,54 kg para as mulheres. As diferenças entre as medidas de estatura ficaram abaixo de 2 cm em ambos os sexos, impactando em uma boa confiabilidade no uso do IMC referido com médias das diferenças de 0,1 kg/m² no sexo masculino e 0,19 kg/m² no sexo feminino. A sensibilidade do diagnóstico de sobrepeso (IMC25 kg/m²) foi de 89,5% entre os homens e de 92,3% entre as mulheres. Já a especificidade foi de 71,4% e 100,0%, respectivamente. No tocante à qualidade global da dieta, O IQD médio foi de 61,9 pontos. Os escores foram baixos (< 5 pontos) para frutas, leite e derivados e sódio. A maioria da amostra (72,1%) apresentou uma dieta com necessidade de melhora. Indivíduos com sobrepeso apresentaram menores escores para cereais e leguminosas, além do IQD total. A análise múltipla mostrou associação independente positiva e ajustada pela energia entre a qualidade da dieta e o tempo de TARV entre as mulheres. Já os homens mais velhos com carga viral indetectável apresentaram maiores pontuações para o IQD. Conclusão: As informações referidas de peso e estatura apresentaram boa confiabilidade e validade quando comparadas às suas respectivas medidas. Em relação à qualidade da dieta, esta foi associada à carga viral indetectável e ao tempo de TARV. Os baixos valores de consumo de frutas e leite e derivados e alto de sódio mostram a importância de intervenções que promovam a adoção de uma alimentação saudável nesta população. / Aims: The main aim was to assess the associated factors to diet quality among adults living with HIV/AIDS on highly active antiretroviral therapy (HAART) in São Paulo, Brazil. Secondary aim was the assessment of the reliability and validity of self-reported weight and height in adults living with HIV/Aids. Methods: Cross-sectional study with 508 men and women, between 20 and 59 years old, who were on HAART for at least three months. There were two research streams: 1) assessment of reliability and validity of self-reported height and weight of adults living with HIV/ AIDS; 2) assessment of the associated factors to diet quality among people living with HIV/AIDS (PLWHA). In order to assess validity of self-reported height and weight sensitivity and specificity analyses were performed. Reliability was evaluated by means of intra-class coefficients. Height and weight were direct measured in a sub-sample. Diet quality was assessed with the use of an adapted Healthy Eating Index (HEI-A) for the studied population. Food intake was collected with a 24-hour Food Recall. Associated factors to diet quality were determined by multivariate linear regression. HEI-A was the dependent variable and demographic, lifestyle, laboratorial, and clinical variables were the independent variables. Analyses were gender-specific. Results: Most of the sample were men (57.7%), mean age of 41.7 years (Standard Deviation - SD = 7.9), and average schooling of 8.3 years (SD=3.7). Mean differences of weight were -0.96 kg for men and -0.54 kg for women. For height, differences were below 2 cm for men and women, leading to a good reliability for the self-reported Body Mass Index (BMI). Overweight (BMI25 kg/m²) diagnosis sensitivity was 89.5% for men and 92.3% for women. Specificity was 71.4% and 100.0%, respectively. HEI-A mean was 61.9. Scores were low (< 5) for fruits, dairy products, and sodium. Among the sample, 5.3% had an adequate diet and 72.1% a diet that needed improvement. Overweight individuals scored lower for grains and beans, as well as for the total HEI-A. Time since HAART start was associated to diet quality among women. Older men who had an undetectable viral load had higher scores of HEI-A. Both models were adjusted by energy. Conclusion: Self-reported weight and height showed good reliability and validity when compared to direct measured weight and height. Regarding diet quality of PLWHA, it was associated with time since HAART start and an undetectable viral load. Low scores for fruits, dairy products, and sodium, as well as an association between nutritional status and diet quality, point out the need for interventions to promote healthy eating among people living with HIV/Aids, taking into consideration differences between women and men.

Objective: The objective of this cross sectional study was to compare the clinical presentation and response to treatments, in HIV positive and TB smear positive patients treated during the pre-Highly Active Antiretroviral Therapy (HAART) and Highly Active Antiretroviral Therapy (HAART) era (2004 and 2007), in St Joseph’s hospital Roma Lesotho. Comparison was done in terms of age, sex, sputum conversion at 2months and 6months end of TB treatment, baseline and 6 months end of TB treatment weight, weight gained and radiological presentation and resolution. Method : It was a cross sectional study design. Data was captured from the TB/HIV register, for pre-HAART era data of patients registered in the 2004 TB/HIV was captured and for the HAART era data of patients registered in the 2007 TB/HIV was captured. Cases were individuals with sputum smear positive tuberculosis and confirmed HIV infection, presenting in the pre HAART era (2004) and in the HAART era (2007). For inclusion in the HAART era, an individual had to be on HAART for at least2 weeks or more. A total of 113 Patients were analysed and 85 patients the HAART era. Comparison of continuous measurements was done with a t-test and categorical measurement was done with a chi-square test. Multivariable logistic regression was used to detect differences between the pre-HAART and HAART era Result: One hundred and thirteen (113) patients were analysed in the pre-HAART era and eighty five (85) in the HAART era. Mean age of presentation was lower in the pre-HAART era 36.1 years compared to HAART era 39.3 years with statistically significant result (p=0.0362). Pattern of sex distribution was similar in both era, (p-value=0.85). Sputum conversion showed statistically significant differences at 2 months, 95.2% of the HAART patients had sputum reverted whereas, 83.2% of the pre-HAART had sputum reversion (p-value=0.009), but no statistically significant result was seen at 6 months (p-value=0.38). Weight did not differ significantly between the two time periods, but there was a statistically significant difference in terms of mean weight gained in Haart era. Patients in the HAART era gained 0.92kg at the end of treatment compared to pre HAART era (p-value=0.001). Radiological presentation and resolution did not differ significantly between the two time periods. (p-value= 0.36). Conclusion : Smear positive TB/HIV co-infected patients in the HAART era were older at presentation, had better sputum conversion at 2 months and improved weight gain at 6 months end of TB treatment. Comparison with a historical control group alone however does not conclusively prove that this effect is due to HAART. Copyright / Dissertation (MSc)--University of Pretoria, 2010. / School of Health Systems and Public Health (SHSPH) / Unrestricted

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

MSc, Paediatrics and Child Health, Faculty of Health Sciences,University of the Witwatersrand / Background To investigate whether in-utero exposure to highly active antiretroviral treatment (HAART) is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV infection. Methods A retrospective observational study was performed on women with CD4 cell counts ≤250 cells/mm3 attending antenatal antiretroviral clinics at two clinics in Johannesburg between October 2004 and March 2007. Low birth weight (<2.5kg) and preterm birth rates (<37 weeks) were compared in those exposed versus unexposed to HAART during pregnancy. Effects of different HAART regimen and duration (<28 weeks or ≥ 28 weeks) were assessed. Results Among HAART-unexposed infants 27% (60/224) were low birth weight (LBW) compared to 23% (90/388) of early HAART-exposed and 19% (76/407) of late HAART-exposed infants (P=0.05). In the early HAART group, older maternal age was associated with LBW and higher CD4 cell count protective against LBW (AOR 1.06, 95% CI 1.00- 1.12 and AOR 0.58, 95% CI 0.46-0.73, P<0.001, respectively). HAART-exposed infants had an increased risk of preterm birth vii (<37 weeks) (15% [138/946] versus 5% [7/147], p=0.001), with early (<28 weeks) nevirapine and efavirenz having the strongest associations with preterm birth (AOR 5.4, 95%CI 2.1-13.7, P<0.001 and AOR 5.6, 95%CI 2.1-15.2, P=0.001, respectively). Conclusion Among infants born to women with CD4 cell counts <250 cells/mm3, HAART exposure was associated with preterm birth, but not with low birth weight. More advanced immunosuppression was a significant risk factor for both LBW and preterm birth, highlighting the importance of earlier HAART initiation in pregnant women, both to optimize maternal health and to improve infant outcomes

MPH, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 2010 / INTRODUCTION Although much focus has been placed towards rapid scale-up of antiretroviral treatment programmes and interventions for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV), very little is known about adherence to highly active antiretroviral therapy (HAART) and loss to follow-up of pregnant women in antiretroviral treatment programmes in the developing world. In this retrospective cohort analysis, we described the baseline characteristics of adult women who were pregnant at the time of HAART initiation (pregnant at start) as well as women who became pregnant during follow-up after starting HAART (pregnant after) and women who never had a pregnancy (not pregnant) during the study period. We evaluated the association of pregnancy status with adherence and loss to follow-up in these three groups of women. MATERIALS AND METHODS Themba Lethu Clinic is an urban public-sector antiretroviral rollout facility in Johannesburg, South Africa. A retrospective analysis was conducted of all adult women initiating HAART at this clinic between January 2005 and December 2007. Clinical data from these patients was analysed for differences in rates of loss to follow-up, and measured adherence rates based on CD4 cell count response and virologic suppression. Regression models were performed to determine independent predictors of adherence and loss to follow-up and compared between the three groups. Survival analysis, in the form of Kaplan-Meier plots and log-rank tests, was used to compare the time to becoming lost to follow up. RESULTS Between 1 January 2005 and 31 December 2007, 5129 women initiated HAART at Themba Lethu Clinic, Johannesburg, South Africa. Of these women, 521 (10.0%) were pregnant at the time of HAART initiation (pregnant at start) and 291 (5.6%) became pregnant during follow-up (pregnant after). Women who were pregnant at start (16.6%) of HAART had less-advanced HIV disease than the not pregnant women and pregnant women after HAART initiation 4608 (89.9%). Overall pregnant women were significantly younger than the not pregnant women and fewer pregnant women had a CD4 <100 cells/mm3 and a WHO stage III of HIV disease. There was no significant difference in the CD4 cell count response and virological suppression between the three groups of women based on pregnancy status at 6 months and 12 months (X2=2.1, p=0.347 and X2=4.4, p=0.111 respectively). However, women pregnant at start were more likely to become lost to follow-up (X2=15.8, P=<.0001) during follow up. In the multivariate Cox logistic regression model, independent predictors of loss to follow-up were pregnancy, baseline CD4 cell count and age at initiation. Being pregnant was significantly associated with being loss to follow-up. CONCLUSIONS Pregnancy is significantly associated with defaulting treatment and becoming lost to follow-up from HAART treatment programmes. Together with being pregnant, young age and a low CD4 at baseline are high risk factors for non adherence and loss to follow-up in this sub-group of the population. Early initiation of HAART with adequate pre-treatment counselling and ongoing adherence support could help improve adherence and retention in care for patients in treatment programmes in resource-limited settings. Interventions to trace patients immediately upon missed appointments would help to reduce the number of patients’ loss to follow-up. Moreover, integration of tuberculosis (TB), antenatal care (ANC) and HIV treatment services may maximize the effectiveness of interventions aimed at reducing the loss to follow-up rate. The initiation of HAART in pregnancy requires strengthened antenatal and HIV services that target women with advanced stage disease.

MSc (Med), Epidemiology and Biostatistics, Faculty of Health Sciences, University of the Witwatersrand / Objectives: To evaluate differences in virologic outcomes between adolescents and pre-adolescents initiated on HAART and to determine the patient baseline variables associated with virologic suppression. Design: Retrospective cohort study using routinely collected clinic and outcome data. Setting: Public sector HIV paediatric facility at Harriet Shezi Children’s Clinic (Chris Hani Baragwanath Hospital) Soweto, South Africa. Patients: HIV infected pre-adolescents (5 to < 11 years) and adolescents (11 to <18 years) initiating HAART between 1 April 2004 and 31 December 2008. Main outcomes and measures: Primary: virologic suppression (HIV viral load ≤ 400 copies/ml) and viral rebound (single HIV viral load ≥ 400 copies/ml after initial suppression) at 24, 48, 72 and 96 week follow up intervals. Secondary: determination of baseline variables associated with virologic suppression. Survival analysis was performed using the Kaplan Meier method and modelling was based on Cox proportional hazards. Results: Both groups exhibited similar incidence rates of virologic suppression by the 24th week from HAART initiation. Adolescents had a slightly lower incidence rate of early virologic suppression in comparison to pre-adolescents (197/100 person years vs. 203/100 person years). However, the observed difference was not statistically significant at 5% significance level (IRR: 0.97, 95%CI: 0.81 - 1.15). In a sub-group of children who had not virologically suppressed by the 24th week (168 days) of follow up, adolescents were 42% less likely to achieve virologic suppression after this time point than pre-adolescents ([IRR: 0.58, 95%CI: 0.35, 0.93). In the sub-group of all female participants, lower hazards of virologic suppression by the 24th week (aHR 0.76, 95%CI 0.59-0.99) and 96th week (aHR 0.70, 0.55-0.90) of follow up were observed among female adolescents when compared with female pre-adolescents. Additionally, clinically advanced disease was observed as a risk factor for non-virologic suppression by the 96th week of follow up among participants of all ages (aHR 0.75, 95%CI 0.64 -0.87). After 60 weeks from the initial virologic suppression, adolescents were twice more likely to experience rebound after this point than pre-adolescents (IRR: 2.33, 95%CI: 1.00 - 5.13). Conclusion: Given the potential for resistant strains of the HIV virus and the public health threat this presents, health care teams face complicated dilemmas regarding initiation of HAART to adolescents, particularly female adolescent patients who are likely to be non-adherent. Findings from the study advocate for intensified adherence and treatment support for all adolescents initiated on HAART to achieve virologic suppression within the first 6 months of treatment, a time after which they have been shown to exhibit inferior virologic suppression rates. Once virologic suppression has been attained, adolescents require prolonged treatment support to maintain long term virologic suppression at levels observed among pre-adolescents. We recommend further research into the comparison of virologic outcomes between pre-adolescents and adolescents on HAART, through prospective study designs. Qualitative study designs are also important to bridge the knowledge gaps on the barriers to HAART encountered by female adolescents.

MPH, Faculty of Health Sciences, University of the Witwatersrand / Background: The increase use of highly active antiretroviral therapy (HAART) among patients with HIV infection and AIDS has led to increasing reports of metabolic abnormalities such as diabetes mellitus, hypertension, dyslipidaemia and obesity. Therefore, it is important to explore the burden of these diseases among HIV infected patients. Objectives: To determine the burden of metabolic diseases (hypertension, diabetes, obesity and dyslipidaemia) in patients attending HIV clinic at the Charlotte Maxeke Johannesburg Academic Hospital (JHBH). Methodology: It was a cross-sectional study. The study population included patients attending JHBH HIV clinic and on HAART for more than one year. A sample size of 304 patients, including 237 females and 67 males partook in this study. Anthropometric measurements were taken from patients and blood samples of these patients were sent to laboratory for lipograms, HbA1c, random glucose, CD4 lymphocytes counts as well as HIV viral load testing. The data was analysed with standard statistical software Epi-info version 6.0. Both descriptive and analytical statistics was used. Results: The prevalence of metabolic syndrome according to the IDF was 20.4 %; obesity (BMI 30 kg/m2) was 16.8% and patients that were overweight (BMI > 25 kg/m2 and BMI < 29.9 kg/m2) was 28.6%; hypercholesterolemia (TC 5.0 mmol/l) = 35.5%; HDL< 1.29 mmol\L in females was 58% and HDL <1.04 mmol/l in males was 36%; elevated triglycerides 1.7 mmol/l was 30% and only 16% was classified as being hypertensive (BP 140/90 mmHg and / or on Hypertensive medication). The majority of the patients (86.2%) had a CD4 lymphocyte count 200 X 106 cells/l and 84% of patients had less than detectable limits for viral loads (VL< 40 copies / μl), which has been reported as optimum levels for metabolic diseases in HAART recipients. Conclusion: These results clearly indicate that there is a growing burden of metabolic diseases among HIV patients on HAART attending the Johannesburg hospital HIV clinic. The current study also indicates that the metabolic disturbances are more frequent in women than in men, except for hypertension.

Introdução: A partir da segunda metade da década de noventa, a oferta de tratamento com a Terapia Antiretroviral de Alta Potência contribuiu para a redução da mortalidade de pessoas vivendo com aids nos locais com acesso universal a medicação. Porém, a introdução de procedimentos efetivos tem sido apontada como associada a desigualdades em saúde, quando fatores sociais dificultam o acesso e a aderência ao tratamento. Objetivo: Descrever a evolução temporal da mortalidade nos bairros de Campinas, verificando se houve declínio após a disponibilização da terapêutica antirretroviral de alta potência em 1997 e se este declínio foi homogêneo entre três agregados de áreas da cidade, ou se foi de algum modo associada com a condição socioeconômica das mesmas. Métodos: Foram avaliadas as taxas de mortalidade por aids em bairros de Campinas, São Paulo, de 1996 a 2012, a fim de testar sua associação com o status socioeconômico da área de residência após o início da oferta universal e sem custo de Terapia Antiretroviral de Alta Potência. Foram calculadas as taxas de mortalidade anuais por aids, ajustadas por sexo e faixa etária, com base em informações oficiais de população e mortalidade. Foi estimada a tendência de declínio da mortalidade por aids, usando o procedimento de auto-regressão de Prais- Winsten para séries temporais. A taxa de declínio anual nos três agregados de bairros da cidade foi comparada segundo índices socioeconômicos estimados para o Índice de Condições de Vida. Resultados: A mortalidade por aids ajustada por sexo e idade em Campinas caiu de 13,6 óbitos/100.000 habitantes em 1996 para 4,6 óbitos /100.000 habitantes em 2012. O decréscimo anual foi de 5,5 por cento (Intervalo de Confiança 95 por cento 3,3 por cento -7,5 por cento ). Não foram observadas diferenças significantes de mortalidade (magnitude e taxa de redução) entre as áreas de moradia. Na faixa etária de adultos (20 a 49 anos), houve menor queda da mortalidade no sexo feminino, principalmente na área de pior status socioeconômico. Conclusões: O programa de tratamento para as pessoas com aids foi efetivo para a redução global da mortalidade devida à doença na cidade de Campinas. A redução de mortalidade foi homogênea entre as áreas, o que é compatível com a hipótese de redução das desigualdades em saúde. Porém, a menor redução na mortalidade de mulheres, na faixa etária de adultos, principalmente na região de pior condição socioeconômica, aponta a persistência de desigualdades sociais em saúde. / Introduction: Since the second half of the 1990s, the provision of highly active antiretroviral therapy (HAART) contributed to the reduction in mortality of people living with AIDS in places with universal access to medication. However, the introduction of effective interventions has been identified as associated with health inequalities, when social factors hinder the access and adherence to treatment. Objective: to describe trends of mortality in the districts of Campinas, checking if there was decline after the release of the HAART in 1997 and if this decline was homogeneous among the three aggregate areas of the city, or was somehow associated with their socioeconomic status. Methods: We assessed AIDS mortality in neighborhoods of Campinas, São Paulo, from 1996 to 2012 in order to compare differences among areas of residence after the introduction of universal, free-of-cost provision of HAART. We estimated annual death rates by AIDS, as adjusted for sex and age, based on official information from population and mortality. The annual percent change of AIDS mortality was calculated using the procedure of Prais-Winsten for auto-regression of time series. We assessed differences of the annual percent change between the three clusters of neighborhoods; their socioeconomic status was informed by a socioeconomic index assessed by local health authorities. Results: The adjusted death rate by AIDS in Campinas reduced from 13.6 deaths/100,000 inhabitants in 1996 to 4.6 deaths/100,000 inhabitants in 2012. The annual percent change was 5.5 per cent (95 per cent Confidence Interval 3.3 per cent -7.5 per cent ). No significant differences of mortality (magnitude and annual percent change) among the living areas was observed. In the age group of adults (20-49 years old), a lower decrease of mortality in women was observed, especially in the area of lower socioeconomic status. Conclusions: The program of treatment for people with AIDS was effective in the city of Campinas, as refers to the overall reduction of mortality due to the disease. This reduction was homogeneous among the areas, which is consistent with the hypothesis of a reduction of inequalities in health. However, the lower reduction in mortality in women in the age group of adults, especially in the region of lower socioeconomic status, indicates the persistence of social inequalities in health.

Philosophiae Doctor - PhD / This thesis firstly reports on the development and characterization of reagent-less and cobalt(III) sepulchrate[Co(Sep)³⁺] mediated biosensor platforms (biosensor platform 1 and biosensor platform 2), with human recombinant heme thiolate, cytochrome P450 3A4 isoenzyme (CYP3A4), as biorecognition component. Secondly, each biosensor platform was evaluated by using an entirely different category of compound as model substrate, with the overall objective being the development of alternative analytical method for the detection and quantification of each of these substrates,by amperometric transduction method. In this regard biosensor platform 1 was evaluated for the detection of 2,4-dichlorophenol, whereas biosensor platform 2 was evaluated for the detection of protease inhibitor (PI) HAART drug, indinavir. Fourthly, this dissertation also reports on the use of genetic engineering as complimentary method during biosensor investigations, as source for continuous supply of catalytically active biological recognition component. With respect to the preparation of the biosensors in particular, biosensor platform 1 was constructed by entrapping the commercially sourced full-length, wild type CYP3A4 on a pre-formed electroactive carrier matrix, consisting of Co(Sep)³⁺–modified nafion membrane on a glassy carbon electrode. In this regard, the nafion-Co(Sep)³⁺ composite was prepared by integrating the Co(Sep)³⁺ species into a pre-formed nafion film through manual drop-coating and mixing methods.