A avaliação do estado nutricional em pacientes com HIV é de grande importância, pois as conseqüências provocadas pelo processo patológico da doença estão associadas com perda de peso corporal, massa magra e desnutrição grave, o que prediz aumento da morbimortalidade. Os valores de linfometria CD4 também têm sido utilizados como preditores a curto e médio prazo para o desenvolvimento de infecções oportunistas, as quais são incomuns em pacientes com CD4 >200 cels/mm3. Partindo deste conhecimento, optou-se por estudar o estado nutricional de homens e mulheres HIV positivos de acordo com a contagem de células CD4. Utilizou-se como parâmetros nutricionais o índice de massa corporal (IMC), a área muscular do braço corrigida (AMBc), albumina sérica e o ângulo de fase (AF). Foram estudados 39 pacientes HIV positivos, acompanhados pelo ambulatório de doenças infectoparasitárias do Hospital Universitário Pedro Ernesto (HUPE/UERJ). Não foi observada desnutrição na população estudada, quando avaliada pelo IMC e albumina em ambos os sexos, independente do número de células CD4. Entretanto, a AMBc e o AF, tanto nos homens quanto nas mulheres, demonstraram comprometimento nos parâmetros de massa magra. Em relação à associação entre os indicadores nutricionais e o número de células CD4, foi observado correlação significante com a AMBc e a albumina no grupo estudado. A correlação de acordo com o sexo manteve-se significante em ambos os grupos para AMBc e com uma tendência positiva (p=0,06) entre o AF e CD4 no grupo dos homens. Portanto, estes resultados demonstram que para avaliar o estado nutricional, principalmente o compartimento de massa corporal magra de pacientes HIV positivos sob terapia antirretroviral, é preciso utilizar indicadores mais sensíveis, mesmo naqueles pacientes com melhor estado de controle da doença. / The assessment of nutritional status in patients with HIV is of great importance, because the consequences caused by the pathological process of the disease are associated with weight loss, lean body mass and severe malnutrition, which predicts increased morbidity and mortality. The values of CD4 linfometria have also been used as predictors of short and medium term development of opportunistic infections, which are uncommon in patients with CD4 counts > 200 cells/mm3. Based on this knowledge, we chose to study the nutritional status of HIV positive men and women according to CD4 cell count. Participants had the following nutritional parameters assessed: body mass index (BMI), corrected arm muscle area (AMA), serum albumin and the phase angle (PA). We studied 39 HIV-positive patients, under treatment in a infectious diseases clinic of the University Hospital Pedro Ernesto (HUPE). None of patients has malnutrition according BMI and albumin in both sexes, regardless of the number of CD4 cells. However, in men and women to AMA and the PA, have demonstrated reductions in parameters of lean body mass. Regarding the association between nutritional indicators and the number of CD4 cells, we observed a significant correlation with the AMA and albumin in the study group. The correlation according to gender remained significant in both groups for AMA and a positive trend (p = 0.06) between the PA and CD4 in males. Therefore these results demonstrate that to assess nutritional status, especially the compartiment of lean body mass in HIV positive patients under antirretrovirals, it is necessary to use more sensitive, even in patients with the best state of disease control.

Thesis (MPhil)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: This study, which was conducted from 1 to 31 October 2012, was aimed at describing the main factors that influence adolescent adherence to antiretroviral treatment in three selected health facilities of Palapye Health District. During the one-month data collection period, 30 adolescents were interviewed using semi-structured interview tools. Different factors influencing adolescent adherence to antiretroviral treatment were highlighted and adherence to such treatment was measured using the method of calculating the percentage of returned pills. The mean adherence level for the entire sample was 76.96%, with common factors contributing to poor adherence among adolescents being found to be the poor processing of disclosure, stigma, the accessibility of health facilities, due distance and waiting time, the nature of social support, and feelings toward taking antiretroviral. Thus, by addressing adolescent adherence to antiretroviral treatment, adolescent-adherence counselling before and during treatment is to be shaped, insisting on the preparation of young patient caregivers for the process of disclosure; the reinforcement of positive messages during consultations; insistence on the importance of disclosing HIV status to others; the implementation of the antiretroviral dispensing outreach at health posts; and exerting effort to reduce the waiting time at health facilities prioritising young patients and adolescents. / AFRIKAANSE OPSOMMING: Hierdie studie, wat vanaf 1 tot 31 Oktober 2012 onderneem is, het ten doel gehad om die hooffaktore te beskryf wat adolessente se getrouheid met antiretrovirale behandeling in drie gekose gesondheidsfasiliteite in die Palapye-gesondheidsdistrik beïnvloed. Semigestruktureerde onderhoude is gedurende die maand lange datainsamelingstydperk met 30 adolessente gevoer. Die studie dui op verskillende faktore wat adolessente se getrouheid met antiretrovirale behandeling beïnvloed, welke getrouheid gemeet is aan die hand van die persentasie teruggestuurde pille. Die gemiddelde getrouheidsvlak vir die algehele steekproef was 76,96%. Algemene faktore wat oënskynlik tot swak behandelingsgetrouheid onder adolessente bydra, is die swak verwerking van MIV-statusonthulling, stigma, die toeganklikheid van gesondheidsfasiliteite, reisafstand en wagtyd, die aard van maatskaplike steun, en gevoelens oor die gebruik van antiretrovirale middels. Hierdie ondersoek na adolessente se getrouheid met antiretrovirale behandeling behoort adolessentberading oor behandelingsgetrouheid voor én gedurende behandeling te rig. Die klem moet in die besonder val op die voorbereiding van die versorgers van jong pasiënte om die onthullingsproses beter te hanteer; die versterking van positiewe boodskappe gedurende konsultasies; die belang van MIV-statusonthulling aan ander; die inwerkingstelling van uitreikaksies om voorskrifte vir antiretrovirale middels by sogenaamde ‘gesondheidstasies’ te resepteer, en daadwerklike pogings om die wagtyd by gesondheidsfasiliteite te verkort, met voorrang aan jong pasiënte en adolessente.

Objectif : Étudier le risque d’hémorragies intracrâniennes et d’infarctus du myocarde chez les patients vivant avec le VIH. Méthode : J’ai réalisé deux études de cohorte au sein de la banque de données de la Régie de l’assurance maladie du Québec. J’ai défini la cohorte des patients VIH-positifs, y ai étudié l’incidence d’hémorragies intracrâniennes et d’infarctus du myocarde, et l’ai comparée à une cohorte VIH-négative de même âge et de même sexe. J’ai étudié l’association entre ces évènements et l’exposition aux antirétroviraux au moyen d’études cas-témoin nichées dans la cohorte des patients VIH-positifs. Résultats : Le VIH est associé à un risque plus élevé d’hémorragies intracrâniennes, particulièrement au stade SIDA. Les patients VIH-positif sont également plus à risque de subir un infarctus du myocarde, et certains antirétroviraux sont associés à un risque plus grand. Conclusion : Les banques de données médico-administratives représentent un moyen valable d’étudier les comorbidités non-infectieuses chez les patients atteints du VIH. / Objective: To study the risk of intracranial hemorrhage, acute myocardial infarction and their determinants in HIV-infected patients. Methods: I conducted two matched cohort studies within the database of the Régie de l’assurance maladie du Québec. I identified the cohort of HIV-infected patients and compared the incidence of intracranial hemorrhage and myocardial infarction with that in an age and sex matched cohort of HIV-negative patients. To study the association between these events and exposure to antiretrovirals, I conducted two matched case-control studies nested in the HIV-positive cohort. Results: HIV-infected patients had increased risk of developing intracranial hemorrhage, particularly if they had AIDS. They were also at greater risk of suffering from myocardial infarction. Exposure to some antiretroviral drugs was associated with greater risk of myocardial infarction. Conclusion: Administrative health data can be used to study the non-infectious complications of HIV infection, but validation studies are needed to evaluate data quality.

Cette thèse propose une description ethnographique et une analyse sociologique de l’arrivée des traitements antirétroviraux (ARV) à Bangui, c’est-à-dire de cette rencontre singulière entre un programme international à l’ampleur inédite et une société locale durement touchée par l’infection. S’appuyant sur trois années de terrain entre 2005 et 2011, la démarche qualitative vise à répondre à la question suivante : de quoi les antirétroviraux sont-ils vraiment l’incorporation ? Les programmes d’accès au traitement constituent un pouvoir thérapeutique qui se structure comme une « politique de la vie » mettant en lien ARV, ONG et une histoire postcoloniale. La distance entre les prétentions et les réalités du pouvoir thérapeutique explique les ambivalences ressenties lors de l’incorporation biologique et sociale des ARV. Le pouvoir thérapeutique dans le contexte social centrafricain se caractériserait alors moins par des formes exclusivement biomédicales de subjectivité, que par un processus d’individuation fragmenté, basé sur des pratiques biomédicales souples, démonstratives et oublieuses. Il apparaît alors clairement que les programmes internationaux de traitement de l’infection à VIH contribuent à produire de l’oubli ou plus précisément à écrire l’oubli à partir des « pratiques scriptuaires »: l’oubli des histoires individuelles enchâssées dans des inégalités sociales insurmontables, mais aussi l’oubli d’une Histoire plus longue qui montre que l’infection à VIH est l’incorporation d’un passé colonial. Prendre un temps pour reconnaître ces temporalités du traitement paraît alors de plus en plus nécessaire pour construire un présent qui émancipe, plutôt qu’il ne répète. / This thesis proposes an ethnographic description and a sociological analysis of the arrival of antiretroviral (ARV) in Bangui. It highlights the encounter between an international program with an unprecedented scale and a local society hardly hit by the HIV infection. The qualitative approach, based on three years of fieldwork from 2005 to 2011, aims at answering the following question: what are ARVs really the incorporation of? Treatment programs represent a therapeutic power that is structured as a « politics of life » linking medicines, NGOs and postcolonial history. The distance between the claims and the realities of therapeutic power explains the ambivalence felt in the biological and social inclusion though ARVs. Eventually, we observe that the therapeutic power in the Central African social context is less characterized by exclusive biomedical forms of subjectivity than by a fragmented process of individuation based on flexible, demonstrative and forgetful biomedical practices It appears then increasingly clear that international programs for the treatment of HIV infection contribute to produce oblivion or more precisely write oblivion with "scriptural practices", which is to say the oblivion of individual stories embedded in insurmountable social inequality, but also the omission of a longer history which shows that HIV infection is the incorporation of a colonial past. Taking time to recognize these temporalities of treatment then appears increasingly necessary to build a present that empowers, rather than repeats. / Réalisé en co-tutelle avec le laboratoire Santé-Individu-Société, Ecole doctorale Interdisciplinaire Sciences et Santé, Université de Lyon, avec l'obtention du grade de docteur en sociologie.

No description available.

A avaliação do estado nutricional em pacientes com HIV é de grande importância, pois as conseqüências provocadas pelo processo patológico da doença estão associadas com perda de peso corporal, massa magra e desnutrição grave, o que prediz aumento da morbimortalidade. Os valores de linfometria CD4 também têm sido utilizados como preditores a curto e médio prazo para o desenvolvimento de infecções oportunistas, as quais são incomuns em pacientes com CD4 >200 cels/mm3. Partindo deste conhecimento, optou-se por estudar o estado nutricional de homens e mulheres HIV positivos de acordo com a contagem de células CD4. Utilizou-se como parâmetros nutricionais o índice de massa corporal (IMC), a área muscular do braço corrigida (AMBc), albumina sérica e o ângulo de fase (AF). Foram estudados 39 pacientes HIV positivos, acompanhados pelo ambulatório de doenças infectoparasitárias do Hospital Universitário Pedro Ernesto (HUPE/UERJ). Não foi observada desnutrição na população estudada, quando avaliada pelo IMC e albumina em ambos os sexos, independente do número de células CD4. Entretanto, a AMBc e o AF, tanto nos homens quanto nas mulheres, demonstraram comprometimento nos parâmetros de massa magra. Em relação à associação entre os indicadores nutricionais e o número de células CD4, foi observado correlação significante com a AMBc e a albumina no grupo estudado. A correlação de acordo com o sexo manteve-se significante em ambos os grupos para AMBc e com uma tendência positiva (p=0,06) entre o AF e CD4 no grupo dos homens. Portanto, estes resultados demonstram que para avaliar o estado nutricional, principalmente o compartimento de massa corporal magra de pacientes HIV positivos sob terapia antirretroviral, é preciso utilizar indicadores mais sensíveis, mesmo naqueles pacientes com melhor estado de controle da doença. / The assessment of nutritional status in patients with HIV is of great importance, because the consequences caused by the pathological process of the disease are associated with weight loss, lean body mass and severe malnutrition, which predicts increased morbidity and mortality. The values of CD4 linfometria have also been used as predictors of short and medium term development of opportunistic infections, which are uncommon in patients with CD4 counts > 200 cells/mm3. Based on this knowledge, we chose to study the nutritional status of HIV positive men and women according to CD4 cell count. Participants had the following nutritional parameters assessed: body mass index (BMI), corrected arm muscle area (AMA), serum albumin and the phase angle (PA). We studied 39 HIV-positive patients, under treatment in a infectious diseases clinic of the University Hospital Pedro Ernesto (HUPE). None of patients has malnutrition according BMI and albumin in both sexes, regardless of the number of CD4 cells. However, in men and women to AMA and the PA, have demonstrated reductions in parameters of lean body mass. Regarding the association between nutritional indicators and the number of CD4 cells, we observed a significant correlation with the AMA and albumin in the study group. The correlation according to gender remained significant in both groups for AMA and a positive trend (p = 0.06) between the PA and CD4 in males. Therefore these results demonstrate that to assess nutritional status, especially the compartiment of lean body mass in HIV positive patients under antirretrovirals, it is necessary to use more sensitive, even in patients with the best state of disease control.

A enzima Paraoxonase-1 (PON1) possui atividades paraoxonase, arilestearase e lactonase, entre outras. É a mais estuda da família das PONs que é composta pela PON1, PON2 e PON3. Sugere-se, que todas atuam inibindo o processo de peroxidação lipídica de moléculas como a lipoproteína de baixa densidade (LDL) e alta densidade (HDL), caracterizando assim um possível papel anti-aterogênico. O gene da PON1 apresenta dois sítios polimórficos, com a troca de uma Gln192Arg (Q/R) e Met55Leu, que estão associados com diferenças na atividade e concentrações séricas da enzima. Por sua vez, indivíduos soropositivos para o HIV-1 apresentam alterações do metabolismo lipídico, que poderiam estar associados a alterações na atividade da PON1 e a terapia antirretroviral (TARV) com inibidores de protease (IP). O objetivo do estudo foi determinar as atividades séricas da PON1 e da arilestearase (ARE), e as freqüências alélicas dos polimorfismos genéticos da PON1 192QR e 55LM, e ainda, avaliar a correlação destes parâmetros com as alterações lipídicas em indivíduos soropositivos para o HIV-1 tratados com IP. No período de Setembro de 2009 até Junho de 2012, 174 indivíduos soropositivos e 46 soronegativos para o HIV-1 foram estudados. Foi realizada a genotipagem dos polimorfismos da PON1 192QR e 55LM através de PCR-RFLP. A atividade sérica da PON1/ARE foi avaliada por espectrofotometria empregando-se como substratos o paraoxon e o fenilacetato, respectivamente. O RNA-HIV-1 foi quantificado pelo método NASBA, e os linfócitos T-CD4+ e T-CD8+ por citometria de fluxo. Os níveis séricos de colesterol total, HDL, LDL, triglicérides (TG), ApoA1 e ApoB100 foram determinados e os anticorpos IgG anti-oxLDL por ELISA. A atividade sérica da PON1 foi inferior nos grupos de soropositivos, p<0,05, porém, a atividade ARE não apresentou diferenças entre os grupos estudados, p>0,05. Ambas as atividades não apresentaram relação com os genótipos PON1 192QR e 55LM, e estes genótipos apresentaram uma freqüência alélica semelhante ao grupo de soronegativos. Os níveis séricos de TG foram superiores nos grupos de soropositivos com TARV, p<0,05, enquanto o grupo tratado com IP apresentou níveis séricos de HDL e Apo-A1 inferiores aos demais grupos, p<0,05. Níveis séricos de Apo-B100, IgG anti-oxLDL, e o índice de risco aterogênico foram superiores no grupo tratado com IP, p<0,05. Concluí-se, que indivíduos soropositivos para o HIV-1 apresentaram alterações no metabolismo lipídico, principalmente nos tratados com IP, que adicionalmente apresentaram um maior índice de risco aterogênico e maiores níveis de anticorpos IgG anti-oxLDL. Estas alterações não apresentaram relação com os polimorfismos PON1 192QR e 55LM da PON1, e demonstraram que a atividade da enzima PON-1 esta diminuída em indivíduos soropositivos para o HIV-1 / The enzyme Paraoxonase-1 (PON1) has paraoxonase (PON), arylesterase (ARE) and lactonase activities, among others. It is the most studied member of PON family which is composed of PON1, PON2 and PON3. It is suggested that all members acts by inhibiting the peroxidation of lipid molecules as the low-density lipoprotein (LDL) and high-density lipoprotein (HDL), characterizing a potential anti-atherogenic effect. The PON1 gene has two mainly polymorphic sites, with an exchange of Gln192Arg (Q/R) and Met55Leu (L/M), which are associated with differences in activity and serum concentrations of the enzyme. In turn, seropositive individuals for HIV-1 show changes in lipid metabolism, which could be associated with changes in the activity of PON1 and highly active antiretroviral therapy (HAART) with protease inhibitors (PI). The aim of this study was to determinate the serum PON and ARE activities of PON1, the allele frequencies of PON1 192QR and PON1 55LM genetic polymorphisms and evaluate the correlation between these parameters and lipid abnormalities in seropositive patients for HIV-1 treated with IP. In the period from September 2009 until June 2012, 174 seropositive individuals and 46 soronegative individuals for HIV-1 were studied. We performed PON1 192QR and 55LM genotyping by PCR-RFLP. Serum activities PON and ARE of PON1 were evaluated by spectrophotometry using paraoxon and phenylacetate, respectively, as substrates. The HIV-1-RNA was quantified by the NASBA method, and lymphocytes T-CD4+ and T-CD8+, by flow cytometry. Serum levels of total cholesterol, HDL, LDL, triglycerides (TG), apoA1 and ApoB100 were determined. IgG anti-oxLDL antibodies were quantified by ELISA. The serum PON1 activity was lower in the seropositive group, p<0.05, however, ARE activity did not differ between groups, p>0.05. Both activities had no relation with the PON1 192QR and PON1 55LM genotype, and these individuals showed an allele frequency similar to the seronegative group. Serum levels of TG were higher in groups of HIV-positive with HAART, p<0.05, while the IP-treated group showed serum levels of HDL and ApoA1 lower than other groups, p <0.05. Serum levels of ApoB100, IgG anti-oxLDL antibodies, and atherogenic risk indices were higher in the group treated with PI, p<0.05. It was concluded that individuals HIV-1-infected showed changes in lipid metabolism, especially in those treated with IP, which additionally showed a higher rate of atherogenic risk and higher levels of IgG anti-oxLDL antibodies. These changes did not correlated with PON1 192QR and 55LM polymorphisms and demonstrated that the activity of PON1enzyme is decreased in individuals seropositive for HIV-1

INTRODUÇÃO: Na história natural da infecção por HIV, um período longo de aproximadamente dez anos precede o desenvolvimento da doença. No entanto, a interação vírus-hospedeiro é caracterizada por um evento dinâmico e não estático. Os modelos matemáticos foram cruciais para revelar o conceito de latência viral, visto que a replicação viral intensa e persistente foi demonstrada através da fase assintomática. Uma contribuição importante demonstrou que a maioria das células que produzia vírus tornava-se infectada em poucos dias. Nosso estudo visa avaliar indivíduos infectados por HIV, investigando o impacto dos esquemas anti-retrovirais iniciais recebidos por eles (monoterapia versus bibiterapia versus HAART) no curso da doença. MÉTODOS: Usamos um banco de dados com 1391 pacientes, atendidos em serviço de referência em São Paulo, com pelo menos seis mensurações consecutivas de carga viral. Utilizamos o modelo linear aplicado à carga viral no plasma e ao número de células CD4+ em sangue periférico para classificar os desfechos em favoráveis ou desfavoráveis. Validamos a escolha da aproximação linear de acordo com dois critérios baseados na estatística c2 e em ( ) 2 2 Q . A associação de cada um desses desfechos e o esquema anti-retroviral inicial prescrito foi avaliada após a análise dos coeficientes angulares da reta de regressão para a carga viral e para o número de células T CD4+. RESULTADOS: Para a maioria dos pacientes com carga viral não-detectável durante o seguimento, nenhum esquema anti-retroviral inicial foi capaz de modificar o desfecho. Os resultados indicam efeito benéfico dos esquemas anti-retrovirais para apenas 20% dos pacientes com viremia persistente. Desfechos desfavoráveis foram associados à maioria dos pacientes com recuperação de viremia tanto de forma transiente ou como no final do seguimento. Para a maioria dos pacientes com viremia intermitente, mas com regularidade no final do seguimento: ou não-detectável ou detectável, os resultados mostram, respectivamente, desfechos favorável e desfavorável, independentemente do primeiro esquema anti-retroviral prescrito. Desfechos distintos foram apresentados por pacientes com carga viral oscilatória, ora detectável ora não-detectável, destacando-se que para a maioria dos pacientes que iniciou o tratamento com duas ou três drogas o desfecho foi favorável, ao passo que aquela que iniciou com uma única droga, exibiu desfecho desfavorável. CONCLUSÕES: As ferramentas da Matemática demonstraram, com sucesso, que o esquema anti-retroviral prescrito inicialmente não está associado à resposta ao tratamento para a maioria dos pacientes analisados. Os desfechos favoráveis podem estar associados a intervenções médicas envolvendo reforço da adesão ou mesmo troca de esquemas terapêuticos durante o seguimento. O aparecimento de linhagens resistentes à terapia antiretroviral e a seleção positiva dessas linhagens pode ser uma explicação para os desfechos desfavoráveis obtidos / In the natural history of HIV infection, a ten-year long asymptomatic period precedes disease development. However, viral-host interaction is a dynamic rather than a static event. Mathematical models have been crucial to rule out the concept of viral latency, since persistent and intense viral replication was demonstrated throughout the asymptomatic phase. One important contribution revealed that most plasma viral producing cells had become infected few days before. The present study aims at evaluating such an interaction in HIV infection, investigating the impact of initial antiretroviral regimens (mono therapy vs. double therapy vs. highly active antiretroviral therapy - HAART) in the course of disease. Using an available database with at least six sequential CD4+ cell counts and HIV viral load assessments of 1391 patients under clinical follow-up at a reference care centre in São Paulo, we classified patients according to a linear approximation model of plasma viral loads and peripheral blood CD4+ cell counts into favourable and unfavourable outcomes. We validated the linear approach according to two criteria, based on c2 and ( ) 2 2 Q . Association between each of these outcomes and the initial prescribed antiretroviral regimen was sought after analyzing the viral load and CD4+ cell counts slopes from the linear model. No particular initial regimen was shown associated with plasma viral undetectability during follow-up. The results point out for a beneficial effect of ART regimens for only 20% patients with persistent vireamia. Unfavourable outcomes were associated with most patients who resumed vireamia transiently or at the end of follow-up. For most patients with intermittent vireamia ending with an undetectable or a detectable viral load, the results indicate favourable and unfavourable outcomes, respectively, regardless of the initial prescribed antiretroviral regimen. Distinct outcomes occurred among patients with oscillatory viral loads, standing out the fact that for most patients who were started on therapy with two or three drugs had a favourable outcome. In contrast, most of those who were started on antiretroviral monotherapy had an unfavourable outcome. Mathematical tools have successfully demonstrated that the initially prescribed ART regimen was not associated with the long-term response to therapy for most analysed patients. Favourable outcomes can be associated to medical interventions including reinforcement of adherence or even changes in therapeutic regimens during follow-up. Emergence and positive selection of ART-resistant viral strains might be hypothesized as implicated in unfavourable outcomes

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Beáta Repeľová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Study of effects of antiretroviral drugs on transmembrane transport of tenofovir disoproxil fumarate across MDCKII - ABCB1 cell monolayer Tenofovir disoproxil fumarate (TDF) - ester prodrug of tenofovir is considered as one of the most frequently used component of combination antiretroviral therapy. Several ways of application and good patients' tolerability is typical for this compound. TDF is a substrate of dug transporter such as P-glycoprotein (P-gp) therefore its efflux activity may limit the bioavailability after oral administration and distribution of TDF. As many of antiretroviral drugs are also substrates or inhibitors of P-gp, drug - drug interactions with TDF at the level of transmembrane transport could be expected. The aim of the diploma thesis was to describe effects of co-administered antiretroviral drugs on transfer of TDF across MDCKII cell monolayer by using bidirectional transport and concentration equilibrium setups. The results of experiments confirmed that TDF is a substrate of P-gp. High values of efflux ratio describing transmembrane transport of TDF across parental cells have been observed. This...

Women and children are often the most affected by pandemics which have swept through the world, and in this regard the HIV/AIDS pandemics is not an exception. The most common route of HIV infection in HIV positive children under 5 years of age is through Mother-To-Child Transmission (MTCT). In spite of the seriousness of this pandemic, the Constitutional Court has found that the measures taken by the South African government with regard to the Prevention of Mother-To-Child Transmission (PMTCT) has fallen short of what the Constitution requires. This dissertation critically reviews the management of the South African PMTCT programme, and discusses the relevant Court decisions. The study finally clarifies the obligations of the South Africa government in the context of PMTCT under the 1996 Constitution and in terms of international law. / Constitutional,International & Indigenous Law / LL.M. (Legal aspects of HIV/AIDS)