This study using a quantitative, descriptive design with a questionnaire investigated cultural, religious and social factors that might impact on ARV treatment in HIV/AIDS-infected women in Botswana. The study found that the majority never missed any doses, a few missed doses once or twice, and a small minority missed more than three times. The respondents’ perception of cultural influence on treatment of HIV/AIDS in women revealed that the majority (70%) believe culture has an influence on the treatment. Social factors also impacted on ARV adherence. A few of the respondents indicated that side effects and the number of pills prevented ARV medication adherence. The main reason for non-adherence, however, was forgetfulness. There had been an improvement in the majority of the respondents’ health status and quality of life. Maximizing adherence is essential. Providers and patients both have responsibilities in this regard. / Health Studies / M.A.(Health Studies)

Novos métodos de remoção do tecido cariado tem sido propostos, entre eles a utilização de lasers, abrasão a ar e químico-mecânico. Este trabalho teve o objetivo de avaliar a influência de diferentes métodos de remoção de cárie na resistência de união de um sistema adesivo autocondicionante. Cinquenta molares humanos cariados extraídos foram desgastados para expor uma superfície plana onde a lesão de cárie se encontrava rodeada por dentina hígida. Os dentes foram divididos em 05 grupos (n=10), com um total de 50 dados, de acordo com o método de remoção do tecido cariado, como segue: G1 - sem remoção; G2 - remoção com lixa; G3 – broca de aço esférica em baixa rotação; G4 - laser de Er, Cr: YSGG e G5 - Carisolv. Procedimentos adesivos foram realizados com o sistema autocondicionante (Clearfil SE Bond – Kuraray – Japão), de acordo com as instruções do fabricante. Um cilíndro de resina composta (Z250- 3M do Brasil) foi construído sobre a superfície com o sistema adesivo e estocados em água (24 horas a 37 0 C). Os corpos de prova foram seccionados verticalmente para obtenção de fatias e em seguida confeccionadas ampulhetas em dentina infectada, afetada e sadia, com área aproximada de 1mm 2. As ampulhetas foram montadas em dispositivos de micro-tração e ensaiados na máquina de teste (Mini-Instron) com velocidade de 0,5mm/min. Os resultados obtidos mostraram que existem diferenças estatisticamente significantes entre os substratos sadio e infectado para o grupo G1e sadio e afetado para os grupos G2, G3 e G5. Em dentina sadia, o método utilizado em G3 resultou em valores de adesão superiores com relação a G4 e G2 foi estatisticamente superior com relação a todos os grupos. Os métodos de remoção de dentina infectada utilizados em G2 e G3 resultaram em valores de adesão superiores com relação a G1(dentina infectada). Desta forma podemos concluir que: o tipo de substrato influencia significativamente na resistência adesiva do sistema autocondicionante testado. A adesão à dentina sadia é mais efetiva que à dentina infectada (G1) e à dentina afetada obtida após remoção do tecido infectado com lixa (G2), broca (G3) e Carisolv (G5). Entretanto, para o laser de Er,Cr:YSGG (G4) não houve evidência amostral que sugerisse maior efetividade na adesão da dentina sadia com relação à dentina afetada. A adesão em dentina sadia mostrou-se mais efetiva quando esta foi instrumentada com lixa. Porém, trata-se de um recurso laboratorial de padronização dos espécimes. A utilização da broca de aço resultou em uma superfície mais favorável a adesão, quando comparada à obtida após irradiação com laser de Er, Cr: YSGG, em dentina sadia. A adesão em dentina infectada é pobre, ficando ressaltada a necessidade da remoção deste tipo de dentina, preferencialmente com lixa ou broca, previamente a adesão com sistema autocondicionante. Para os demais métodos de remoção da dentina infectada testados, não houve evidência amostral para se detectar a existência de diferenças significantes na resistência adesiva em dentina afetada. / New methods for carious dentine removal have been proposed, such as, lasers and chemo-mechanical. This in vitro study aimed to evaluate the influence of caries removal methods (steel burs, Er, Cr: YSGG laser and Carisolv) on microtensile bond strength of self-etching adhesive systems. 50 extracted carious human molars were ground to expose flat surfaces where caries lesion was surrounded by normal dentine. Teeth were divided into 5 groups (n=10), with 50 original data, according to the removal method used: G1 - no removal; G2 - abrasive paper, G3 - steel burs; G4 – Er, Cr: YSGG laser (79, 61 J/cm 2 ) and G5 – Carisolv. Surfaces were bonded with Clearfil SE Bond, according to manufacturers’ instructions. A crown was built up using composite resin (Z250- 3M Brasil). After storage in water (24 h, 37 0 C), teeth were vertically serially sectioned into slices and trimmed into an hourglass shape with about of 1mm 2 area at the adhesion interface, that contained either infected, caries affected and normal dentine. Samples were tested in tension in a Instron machine at 0,5mm/min. Results showed that there is a significant difference between tested groups (p< 0.005). Significantly lower results were found for caries infected dentin when compared to normal dentin values (G1). A significant difference was also found when caries affected and normal dentin were compared (G2, G3, G5). In normal dentin, G2 showed better bond strenght than another groups and G4 showed lower results than G3. G2 and G3 caries infected dentin removal methods showed better bond strength than the other groups when compared with G1 (caries infected dentin). The results indicated that: bond strength of a self-etching system to normal dentin was better than to caries infected (G1) and caries affected dentin after the use of abrasive paper (G2), round steel bur (G3) and Carisolv (G4). However, there was no difference between caries affected and normal dentin after the use of ErCr:YSGG laser (G4); abrasive paper is a laboratorial method to create smear layer and it was responsable for the best bond strength to normal dentin. The usage of Er, Cr: YSGG laser negatively altered adhesion of self-etching system on normal dentin when compared with round steel bur; infected dentin is not an adequate substrate for adhesion. Abrasive paper and round steel bur are the best caries infected dentin removal methods. There were no difference in bond strength to caries affected dentin when the other methods were used.

Tuberculosis remains a major public health problem and one of the leading causes of death worldwide. Human genetic factors determine susceptibility to M. tuberculosis (M. tb) infection and predispose to clinical TB. Genome-wide association studies (GWAS) aim to discover human genes associated with susceptibility to TB. Recently, a GWAS conducted by our lab identified a new TB-associated gene ASAP1 that encodes an Arf GTPase-activating protein (GAP). ASAP1 is known to be involved in regulation of actin and membrane remodeling. My Ph.D. included three projects. In my first project, I used RNAi and CRISPR-Cas9 technologies to study the role of ASAP1 in dendritic cells and macrophages, cells that play critical roles during mycobacterial infection. I demonstrated that in these cells ASAP1 is essential for migration and phagocytosis of mycobacteria. I characterized proteins that ASAP1 interacts with during mycobacterial infection. Finally, I found that the ASAP1-mediated pathway regulates expression of a large number of the immune response genes. These findings emphasize the important role of ASAP1 in mycobacterial infection and explain its involvement in TB pathogenesis. In my second project, I was involved in a large study conducted by our laboratory that characterized transcriptional responses to M. tb infection in macrophages from a cohort of 144 healthy subjects. We used RNA-Seq to study transcriptomes of the infected and non-infected macrophages and identified differentially expressed genes. We also genotyped DNA polymorphisms of these subjects and studied the association between genetic variants and levels of gene expression, which allows us to identify expression quantitative trait loci (eQTLs), i.e., DNA polymorphism that affect gene expression. In particular, we identified an eQTL located in the TLR10-TLR1-TLR6 gene cluster. In non-infected macrophages, a group of polymorphisms in this region was associated in cis with the level of expression of TLR1, but not of the other two TLR genes. In M. tb-infected macrophages the same polymorphisms were associated in trans with levels of expression of 37 genes. This network includes essential immune response proteins, including multiple cytokines and chemokines. The discovery of this TLR1-driven network will help to better understand mechanisms of macrophage responses to mycobacterial infection. Our study also identified a DNA polymorphism located upstream of the ARHGAP27 gene, regulating its expression in infected and non-infected macrophages. In our GWAS this polymorphism was associated with TB risk, which implicated ARHGAP27 in TB pathogenesis. The ARHGAP27 protein is a Rho-GAP involved in the endocytic pathway. In my third project, I used CRISPR technology to establish the ARHGAP27-knockout macrophage cell model and characterized the function of ARHGAP27, showing that it is involved in cell migration and phagocytosis of mycobacteria. Taken together, my studies highlighted functional mechanisms implicating TB-associated GAP proteins ASAP1 and ARHGAP27 in mycobacterial infection and TB pathogenesis.

Biofilmes são comunidades bacterianas complexas encapsuladas em matrizes poliméricas autoproduzidas e podem se desenvolver em superfícies inertes ou tecidos vivos. A formação do biofilme é um importante fator de virulência, pois permite à bactéria resistir às respostas do hospedeiro e à terapia antimicrobiana. Devido a essa elevada resistência aos antimicrobianos, é difícil estabelecer uma estratégia eficaz para o tratamento de infecções com formação de biofilmes, levando a falhas na erradicação das mesmas. Nesse contexto, o objetivo do presente estudo é desenvolver um modelo farmacocinético/farmacodinâmico (PK/PD) para descrever o efeito do ciprofloxacino (CIP) na presença de biofilmes de Pseudomonas aeruginosa (ATCC 27853), visto que a modelagem PK/PD de antimicrobianos é uma ferramenta útil na escolha de regimes posológicos que atinjam o efeito bactericida máximo, minimizando o desenvolvimento de resistência. Para atingir esse objetivo, inicialmente um método analítico por CLAE/fluorescência foi desenvolvido para quantificar o CIP em amostras de plasma e microdialisado. O método desenvolvido foi simples, rápido e com sensibilidade adequada para corretamente caracterizar a farmacocinética plasmática e pulmonar do CIP. Posteriormente, um modelo animal de infecção pulmonar crônica foi adaptado da literatura e padronizado, permitindo a investigação da distribuição pulmonar do CIP em ratos Wistar sadios e infectados. Para tal, bactérias foram imobilizadas em beads de alginato a fim de manter a infecção por até 14 dias com cargas bacterianas superiores à 108 UFC/pulmão. Estudo de microdiálise foi então conduzido para avaliar as concentrações livres de CIP após administração intravenosa de 20 mg/kg. A análise não-compartimental (NCA) e a modelagem farmacocinética populacional (PopPK) dos dados foram realizadas nos softwares Phoenix® e NONMEM®, respectivamente. Diferenças significativas foram observadas no clearance plasmático (1,59 ± 0,41 L/h/kg e 0,89 ± 0,44 L/h/kg) e na constante de eliminação (0,23 ± 0,04 h-1 e 0,14 ± 0,08 h-1) para ratos sadios e infectados, resultando em uma exposição plasmática maior nos animais infectados (ASC0-∞ = 27,3 ± 12,1 μg·h/mL) quando comparados com os animais sadios (ASC0-∞ = 13,3 ± 3,5 μg·h/mL) ( = 0,05). Apesar da maior exposição plasmática, quando comparados com os animais saudáveis (fT = 1,69), animais infectados apresentaram uma penetração pulmonar quatro vezes menor (fT = 0,44). Diferenças na constante de eliminação pulmonar não foram observadas. Dados plasmáticos e pulmonares foram simultaneamente descritos por modelo PopPK constituído de compartimentos venoso e arterial, dois compartimentos representativos de duas regiões pulmonares distintas e dois compartimentos periféricos, representando outros tecidos que não os pulmões. Um clearance pulmonar foi adicionado ao modelo apenas para os dados de microdiálise dos animais infectados (CLlung = 0,643 L/h/kg) afim de explicar a exposição tecidual diminuída. O modelo desenvolvido descreveu, com sucesso, os dados plasmáticos e teciduais de animais sadios e infectados, permitindo a correta caracterização das alterações observadas na disposição plasmática e pulmonar do CIP decorrentes da infecção com biofilme. Para os estudos de farmacodinâmica, o efeito bactericida do CIP frente a biofilmes e células planctônicas de P. aeruginosa foi simultaneamente avaliado através do uso de curvas de morte bacteriana. Para a construção destas curvas, biofilmes de P. aeruginosa foram formados na superfície de blocos de acrílico e sua formação foi confirmada pelo ensaio cristal violeta e por microscopia eletrônica de varredura. Os blocos foram expostos a concentrações constantes de CIP (de 0,0625 a 10 μg/mL) e, em tempos pré-determinados, células planctônicas e de biofilmes eram amostradas para quantificação. Um modelo semi-mecanístico que incorpora um modelo Emax sigmoidal foi utilizado para descrever o efeito do CIP frente a ambos estilos de vida bacteriano. Uma subpopulação pré-existente com menor suscetibilidade ao CIP foi incluída no modelo e o efeito do CIP nesta subpopulação também foi descrito pelo modelo Emax sigmoidal. A comparação dos parâmetros estimados pelo modelo demonstrou que o efeito in vitro do CIP é maior para as células planctônicas (EC50 = 0,259 mg/L e 0,123 mg/L e Emax = 2,25 h-1 e 5,59 h-1 para biofilmes e planctônicas, respectivamente). A potência estimada do CIP para a subpopulação resistente foi muito menor para ambos estilos de vida bacteriano (EC50 = 2,71 mg/L e 1,15 mg/L para biofilmes e planctônicas, respectivamente). Os modelos desenvolvidos podem ser utilizados para a simulação de cenários não testados e servir como uma ferramenta para guiar a escolha dos regimes posológicos adequados, contribuindo para o sucesso terapêutico no tratamento de infecções associadas à biofilmes. / Biofilms are complex bacterial communities enclosed in self-produced polymeric matrices that can develop in inert surfaces or living tissues. Biofilm formation is an important virulence factor that allows bacteria to resist host responses and antibacterial agents. Due to this high resistance to antibiotics, it is difficult to establish an efficacious strategy for treatment of infections with biofilm formation leading to failure in infection eradication. In this context, the goal of this study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the antimicrobial effect of ciprofloxacin (CIP) in the presence of biofilms of Pseudomonas aeruginosa (ATCC 27853), since PK/PD modeling for antibacterial agents can be a useful tool to choose dosing regimens and to achieve the maximum bactericidal effect, minimizing the development of resistance. To reach this goal, firstly an analytical method based on HPLC/fluorescence was developed in order to quantify CIP in plasma and lung microdialysate. The developed method was simple, fast and with enough sensibility to proper characterize CIP plasma and lung pharmacokinetics. Secondly, an animal model of chronic lung infection was adapted from literature and standardized, allowing the analysis of CIP lung distribution in infected and healthy Wistar rats. Bacteria were immobilized in alginate beads prior to inoculation to Wistar rats in order to sustain the pneumonia for 14 days, maintaining a bacterial load superior to 108 CFU/lung. A microdialysis study was then conducted to evaluate free CIP concentrations after an intravenous administration of 20 mg/kg. Non-compartimental analysis (NCA) and populational PK modeling (PopPK) of the data were performed in Phoenix® and NONMEM®, respectively. Statistical differences were observed in the plasma clearance (1.59 ± 0.41 L/h/kg and 0.89 ± 0.44 L/h/kg) and elimination rate constant (0.23 ± 0.04 h-1and 0.14 ± 0.08 h-1) for healthy and infected rats, respectively, resulting in a significantly higher CIP plasma exposure in infected rats (AUC0-∞ = 27.3 ± 12.1 μg·h/mL) compare to healthy animals (AUC0-∞ = 13.3 ± 3.5 μg·h/mL) ( = 0.05). Besides the plasma exposure, a four times lower pulmonary penetration was observed in infected rat’s lungs (fT = 0.44) in comparison to healthy animals (fT = 1.69), with no significant differences in the lung elimination rate constant. Plasma and lung data were simultaneously fitted using a PopPK model consisting of an arterial and a venous compartment, two compartments representing different regions of the lungs and two peripheral distribution compartments, representing tissues other than lungs. A lung clearance was added to the model for infected animals (CLlung = 0.643 L/h/kg) to explain the lower tissue exposure. The model successfully described the plasma and microdialysis data from both, healthy and infected rats and allowed to correctly describe the changes in CIP plasma and lung disposition in biofilm infections. For the pharmacodynamic studies, CIP bactericidal effect against Pseudomonas aeruginosa biofilms and planktonic shedding cells were simultaneously evaluated using the time-kill curves approach. For the time-kill curves construction, P. aeruginosa biofilms were formed in acrylic blocks, which was confirmed by the crystal violet assay and scanning electron microscopy. The blocks were placed in flasks containing Mueller-Hinton growth medium and exposed to constant CIP concentrations (ranging from 0.0625 to 10 μg/mL). At pre-determined time points, biofilm and planktonic cells were sampled for bacterial counting. A mechanism-based model which incorporates a sigmoidal Emax model was used to describe the CIP effect against P.aeruginosa in both llifestyles, biofilm and planktonic. The presence of a pre-existing resistant subpopulation was included in the model and also modeled with a sigmoidal Emax model to describe CIP effect in this subpopulation. Comparison of the parameter estimates showed that the in vitro effect of CIP is higher for planktonic cells (EC50 = 0.259 mg/L and 0.123 mg/L and Emax = 2.25 h-1 and 5.59 h-1 for biofilm and planktonic cells, respectively). CIP potency was much lower for the resistant subpopulation, for both bacteria lifestyles (EC50 = 2.71 mg/L and 1.15 mg/L for biofilm and planktonic, respectively). The developed models can be used to simulate untested scenarios and serve as a tool to guide dosing regimen selection, contributing for the therapeutic success of treatments of biofilm-associated infections.

Made available in DSpace on 2016-08-19T17:47:09Z (GMT). No. of bitstreams: 1 Arnaldo Muniz Garcia.pdf: 655892 bytes, checksum: f9f5eda07bd90764780889b563437e7f (MD5) Previous issue date: 2004-01-28 / A cohort prospective study was carried with 350 dogs of various ages at localities Vila Nova and Bom Viver in the municipality of Raposa-MA, from March of 2002 to December of 2003. The objective is to avaluate the behavior of L. (L.) chagasi infection. The chosen areas are a result of the disordered occupation process, contributing with 60% of LVH and LVC cases that were notified by the municipal district. At first, the procedure was made by doing the populational inquiry the two places by means of canine census. The study was processed in two phases, with interval of 7 months among the same ones. In the first phase, 350 dogs participated of the study and by a visiting process a questionnaire with epidemiological, demographical, clinical and behavioral data about the dogs was applied. The testing of Montenegro intradermoreaction (IDRM) was made with the antigen of L. (L.) amazonensis and adapted for dogs, serological examination testing Enzyme Linked Immunsorbent Assay (ELISA), clinical e parasitical were also made in positive animals to IDRM and/or ELISA tests. Starting from clinical and immunological parameters already referred in literature, were defined four diagnoses categories, classifying the dogs according to its evolutionary course in not infected dogs (195), infected (100), Oligosymptomatic sick (41) and polysymptomatic sick (14). The second phase was accomplished with application of the same tests of the first phase with 230 dogs, that reduction was due in function of the losses (36,28%) caused by death, address change and missing. The positive dogs for an or both tests were accompanied bimonthly with reevaluation of the clinical exams. The initial and final prevalence and incidence of the infection were 8,57%, 6,52% and 8% for IDRM; by ELISA 39,71%, 32,6% and 16%; for ELISA and IDRM 44,29%, 37,39% and 21,6% respectively. In what the clinical form refers, the dogs were classified in the following way: infected (28,57%), oligosymptomatic sick (11,71%) and polysymptomatic sick (4%). in agreement with the statistical analyses not adjusted and adjusted, the variable age, race, secondary lesion, physical condition and place were associated the infection for L. (L.) chagasi. The infection for L. (L.) chagasi was present in 52,97% of the canine population of Vila Bom Viver and 34,55% in Vila Nova, demonstrating that in endemic area happens the intense and active circulation of Leishmania. / Realizou-se um estudo de coorte prospectivo com 350 cães com idades variadas nas localidades de Vila Nova e Bom Viver no município da Raposa-MA no período de março de 2002 a dezembro de 2003, com o objetivo de avaliar o comportamento da infecção por L. (L.) chagasi. As áreas escolhidas são resultantes do processo de ocupação desordenada, contribuindo em média com 60% dos casos de LVH e LVC notificados pelo município. Procedeu-se inicialmente com o inquérito populacional nas duas localidades por meio do censo canino. O estudo processou-se em duas fases, com intervalo de 7 meses entre as mesmas. Na primeira fase participaram do estudo 350 cães, e por meio de visita casa/casa aplicou-se um questionário com dados epidemiológicos, demográficos, clínicos e comportamentais dos cães. Realizou-se o teste de intradermorreação de Montenegro (IDRM) com antígeno de L. amazonensis e adequado para cães, teste sorológico Enzyme Linked Immunsorbent Assay (ELISA), clínico e parasitológico dos animais positivos para os testes IDRM e/ou ELISA. A partir de parâmetros clínico e imunológico já referidos na literatura, foram definidas quatro categorias de diagnóstico, classificando os cães segundo o seu curso evolutivo em cães não infectados (195), infectados (100), doente oligossintomático (41) e doente polissintomático (14). A segunda fase foi realizada com aplicação dos mesmos testes da primeira fase com 230 cães, essa redução deveu-se em função das perdas (36,28%) ocasionadas por óbitos, mudança de endereço e desaparecidos. Os cães positivos para um ou ambos os testes foram acompanhados bimestralmente com reavaliação dos exames clínicos. A prevalência inicial, final e incidência da infecção foram 8,57%, 6,52% e 8% por IDRM; por ELISA 39,71%, 32,6% e 16%; por ELISA e IDRM 44,29%, 37,39% e 21,6% respectivamente. No que se refere a forma clinica, os cães foram classificados da seguinte forma: infectados (28,57%), doente oligossintomático (11,71%) e doente polissintomático (4%). De acordo com as análises estatísticas não ajustada e ajustada, as variáveis idade, raça, lesão secundária, condição física e localidade foram associadas a infecção por L. (L.) chagasi. A infecção por L. (L.) chagasi estava presente 52,97% da população canina de Vila Bom Viver e 34,55% em Vila Nova, demonstrando que em área endêmica ocorre a intensa e ativa circulação da Leishmania.

Weight loss among HIV-infected African American women (AAW), results in the fall of the cluster of differentiation (CD4) cell count and an increase in the viral load. There are 48,126 HIV-infected AAW who reported weight loss within the first year. AAW who report more than 10% weight loss within the first year progress to AIDS due to a deficiency in micronutrients and poor linkage to care. The phenomenon that occurs with individuals living with HIV does not necessarily occur among individuals who have cancer, heart disease, or some other life-threatening illness, and this phenomenon indicates a direct threat to the individual's physical, mental, and social survival beyond the effects of chronic diseases. Using the health belief model in this study helped emphasize the physical change that occurs during weight loss among HIV-infected AAW. The research questions addressed if there was a direct correlation between the use of micronutrients and the decrease in weight, decrease in CD4 cell count, and the increase in viral load. The results of the multilinear regression revealed there was direct correlation between the use of micronutrients and the increase/maintain in weight, an increase in CD4 cell count, and a decrease in the viral load, thus promoting the need for more research and funding. The need to educate HIV-infected AAW on the use of micronutrients was evident. Providing research to providers on changes in standard of care for HIV-infected AAW would allow for an increase in the social, economic, and personal impact on the way an individual approaches care and treatment to prevent the progress to AIDS.

Les érythrocytes sont un modèle pour l'étude du transport des ions, des nutriments et de divers solutés au travers de la membrane cellulaire. L'identité moléculaire, la régulation et rôle physiologique des canaux ioniques sont pas clairement établis malgré leur implication évidente dans des processus physiologiques comme la sénescence ou pathologiques comme la drépanocytose ou le paludisme. Le présent travail de thèse a fait appel à la technique du 'patch-clamp' et à diverses méthodes biochimiques pour démontrer que: 1/ La diversité des courants anioniques enregistrés au travers de la membrane de l'érythrocyte humain sain, ou infecté par P. falciparum, correspond à différents états d'activité d'un type unique de canal 'maxi-anionique' comportant des niveaux de conductance, des modes d'activation et des propriétés pharmacologiques variables selon les conditions physico-chimiques. 2/ L'identité moléculaire de ce canal anionique est de type 'voltage dependent anion channel (VDAC)'. Il est l'une des trois composantes d'un récepteur 'peripheral-type benzodiazepine receptor (PBR)' présent dans la membrane érythrocytaire. 3/ Le canal VDAC, généralement peu actif correspond, lorsqu'il est activé, à la nouvelle voie de perméation 'new permeability pathway' décrite dans la membrane de l'érythrocyte infecté par P. falciparum. L'activation résulte alors en partie de l'insertion dans la membrane érythrocytaire de protéines plasmodiales de type 'Ring-infected Erythrocyte Surface Antigen (RESA). Ce travail contribue à l'élucidation de la nature exacte des canaux ioniques présents dans la membrane érythrocytaire et avance une hypothèse unificatrice quant au rôle joué par ces canaux.

<p>Background: Although clinicians encounter antimycobacterial treatment in Human mmunodeficiency (HIV)-infected children as one of the most common treatments coadministered with antiretroviral treatment (ART), quantitative data on the extent of antimycobacterial treatment among HIV-infected children at the time of commencement of ART and at different times during ART is scarce. The baseline risk factors associated with being on both ART and antimycobacterial treatments are not known and it remains to be elucidated how the different exposure factors impact on the antimycobacterial treatment-free survival of children who begin ART without antimycobacterial treatment.Objectives: To describe the prevalence of antimycobacterial treatment among children at the time of starting ART and the antimycobacterial treatment-free survival after starting ART. Design: A retrospective cohort study based on record reviews at the Harriet Shezi children&lsquo / s clinic (HSCC).Population: HIV-infected children less than fifteen years of age presumed ART na&iuml / ve started on ART at HSCC.Analysis: A descriptive analysis of the prevalence of antimycobacterial treatment at time of start of ART was done. Kaplan Meier (KM) survival curves were used to determine the antimycobacterial treatment-free survival and logistic regression was used to analyze the association between baseline factors and future antimycobacterial treatment among children who had no antimycobacterial treatment at time of start of ART. Results: The prevalence of antimycobacterial treatment at the time of starting ART was 518/1941 (26.7%, 95% confidence interval (CI): 24.7-28.7). Among children who started ART without antimycobacterial treatment, the KM cumulative probability of antiretroviral and antimycobacterial (ART/antimycobacterial) co-treatment in the first 3 months of starting ART was 4.6% (95% CI: 4.1- 5.2), in the first 12 months it was 18.1% (95% CI: 17.0-19.2) and in the first 24 months of starting ART it was 24% (95% CI: 21.9-25.1). Survival analysis suggested that children with high baseline viral load, advanced World Health Organization (WHO) stage of disease, very low normalized weight for age (waz) and very young age (less than one year) at start of ART had significantly reduced antimycobacterial treatment-free survival (log rank p &lt / 0.05) in the first two years of starting ART. In the logistic regression model, age less than one year {Odds ratio (OR): 3.7 (95% CI: 2.2-6.0 / p &lt / 0.0001)} and very low weight for age Z-score (waz &lt / -3) {OR / 2.2 (95% CI: 1.4-3.6 / p = 0.0015)} were the two critical risk factors independently associated with future antimycobacterial treatment. Conclusions: Antimycobacterial treatment is extremely common among HIV-infected children at the time of starting ART and early after starting ART and the incremental risk of being on ART/antimycobacterial co-treatment decreases with time on ART. The results emphasize the need for a heightened and careful alertness for mycobacterial events especially among children starting ART with severe malnutrition and those who start ART at age less than one year. The results further suggest that it is probably optimal to start ART in children before their nutritional status has deteriorated severely in the course of the HIV disease so that they get protection against mycobacterial events by early ART.</p>

<p>Background: Although clinicians encounter antimycobacterial treatment in Human mmunodeficiency (HIV)-infected children as one of the most common treatments coadministered with antiretroviral treatment (ART), quantitative data on the extent of antimycobacterial treatment among HIV-infected children at the time of commencement of ART and at different times during ART is scarce. The baseline risk factors associated with being on both ART and antimycobacterial treatments are not known and it remains to be elucidated how the different exposure factors impact on the antimycobacterial treatment-free survival of children who begin ART without antimycobacterial treatment.Objectives: To describe the prevalence of antimycobacterial treatment among children at the time of starting ART and the antimycobacterial treatment-free survival after starting ART. Design: A retrospective cohort study based on record reviews at the Harriet Shezi children&lsquo / s clinic (HSCC).Population: HIV-infected children less than fifteen years of age presumed ART na&iuml / ve started on ART at HSCC.Analysis: A descriptive analysis of the prevalence of antimycobacterial treatment at time of start of ART was done. Kaplan Meier (KM) survival curves were used to determine the antimycobacterial treatment-free survival and logistic regression was used to analyze the association between baseline factors and future antimycobacterial treatment among children who had no antimycobacterial treatment at time of start of ART. Results: The prevalence of antimycobacterial treatment at the time of starting ART was 518/1941 (26.7%, 95% confidence interval (CI): 24.7-28.7). Among children who started ART without antimycobacterial treatment, the KM cumulative probability of antiretroviral and antimycobacterial (ART/antimycobacterial) co-treatment in the first 3 months of starting ART was 4.6% (95% CI: 4.1- 5.2), in the first 12 months it was 18.1% (95% CI: 17.0-19.2) and in the first 24 months of starting ART it was 24% (95% CI: 21.9-25.1). Survival analysis suggested that children with high baseline viral load, advanced World Health Organization (WHO) stage of disease, very low normalized weight for age (waz) and very young age (less than one year) at start of ART had significantly reduced antimycobacterial treatment-free survival (log rank p &lt / 0.05) in the first two years of starting ART. In the logistic regression model, age less than one year {Odds ratio (OR): 3.7 (95% CI: 2.2-6.0 / p &lt / 0.0001)} and very low weight for age Z-score (waz &lt / -3) {OR / 2.2 (95% CI: 1.4-3.6 / p = 0.0015)} were the two critical risk factors independently associated with future antimycobacterial treatment. Conclusions: Antimycobacterial treatment is extremely common among HIV-infected children at the time of starting ART and early after starting ART and the incremental risk of being on ART/antimycobacterial co-treatment decreases with time on ART. The results emphasize the need for a heightened and careful alertness for mycobacterial events especially among children starting ART with severe malnutrition and those who start ART at age less than one year. The results further suggest that it is probably optimal to start ART in children before their nutritional status has deteriorated severely in the course of the HIV disease so that they get protection against mycobacterial events by early ART.</p>

Thesis (MPhil)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: The aim of the study was to investigate to what extent the availability of antiretroviral treatment has influenced sexual risk behavior practices in people living with HIV and AIDS (PLWHA) in order to provide suggestions to improve HIV prevention messages. The study was conducted among adult HIV patients on ART aged 18 and above and affiliated to the Network of Zambian People Living with HIV/AIDS (NZP+) in Lusaka District. A purposive sampling method was used to select study units and a sample of 40 was selected. Data was collected from participants using a self-administered questionnaire. SPSS version 20 software computer package was used to analyze data. Chi- square was used to measure associations between dependent variables (risky sexual behavior and initiation of ART) and the independent variable (duration of time on ART). With the confidence interval set at 95%, the P value was used to ascertain the degree of significance by using the decision rule which rejects the null hypothesis if P value is equal or less than 0.05. The findings revealed that the participant's mean age was 2.8 ± 1.3 SD. More than half (68%, n=27) of the participants had adequate knowledge on HIV prevention while 90% (n=36) of participants had a good (positive) attitude towards ART. 82.5% (n=33) of the participants on ART had sexual intercourse in the last 6 month, and 21.2% (n=7) of these did not use a condom for secondary prevention. There was no significant correlation between being on ART and having sexual intercourse, condom usage or number of sexual partners OR (P value of 0.45 and 0.85), (P values 0.37 and 0.5) and (P value 0.34 and 0.57) respectively. In multivariable analysis, the majority of the respondents (35.5%, n=11) indicated that continued sensitization would improve HIV prevention messages to support communities affected. Few (29%, n=9) stated that: "promoting abstinence among the youths or use of a condom for those that are sexually active and intensifying VCT campaign would reduce HIV transmission" and 7% (n=2) of the respondents suggested that; "involving the families and communities affected, civic, religious, and traditional leaders to educate both the young and adult citizens in schools, colleges and churches to support PLWH and fight against HIV-related stigma and discrimination. Stellenbosch University https://scholar.sun.ac.za iii A significant association was not found between an increase in risky sexual behavior or an upsurge in the occurrence of unprotected sex, initiation of ART and duration of being on ART. The majority (83%, n=15) of the respondents on ART for less than sixty months had protected sexual intercourse and 73% (n=11) on ART for sixty months and above also used protection. This association was statistically not significant (Chi-square value 2.95. P value > 0.05). However; other studies need to explore these subjective interpretations further. / AFRIKAANSE OPSOMMING: Nie beskikbaar