Dissertations / Theses on the topic 'Pharmaceutic Aids'

Bibliography: leaves 106-114.
HIV IAIDS death and mortality rates have proven to be one of the largest threats to the economies of many developing countries, in particular Zimbabwe. Twenty five percent of the adult population in Zimbabwe is HIV positive and it is estimated that at least 2000 people die every week of the disease. Consequently, there is an urgent need to find means and ways of reducing the number of premature deaths due to AIDS. Access to affordable drugs will have great impact on reducing these premature deaths in the country. However high AIDS and opportunistic infections drug prices have rendered these medicines unaffordable and inaccessible to the vast majority of the population infected with the virus. Moreover the majority of the population has to meet most of its drug cost through out of pocket payments.

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O fortalecimento das políticas de Assistência Farmacêutica aos usuários com HIV/AIDS é de grande importância para garantir a sustentabilidade do programa, principalmente pelos altos custos envolvidos para sua implantação e execução. Neste trabalho foi realizada uma avaliação da Assistência Farmacêutica em HIV/AIDS no município de Niterói, com ênfase no seu gerenciamento. O trabalho teve como objetivo responder duas perguntas avaliativas: As condições de estrutura e os processos de trabalho existentes são adequados para que se exerça uma assistência farmacêutica de qualidade às pessoas vivendo com HIV/AIDS (PHVA) atendidas no município de Niterói? As condições de estrutura e os processos de trabalho existentes são adequados para que se garanta o acesso aos medicamentos ARV e para infecções oportunistas às PHVA atendidas no município de Niterói? O desenho da avaliação foi o de um estudo de caso, e a abordagem utilizada foi uma avaliação normativa com foco na qualidade, envolvendo análise da estrutura, do processo e dos resultados, através da construção de um modelo lógico teórico. Das oito UDM existentes no município, seis foram avaliadas neste trabalho. Foram construídas matrizes de relevância e de análise e julgamento, em que os indicadores foram divididos em quatro grupos, de acordo com os componentes da assistência farmacêutica sob a responsabilidade do município descritos no modelo lógico. Os indicadores foram inicialmente analisados individualmente, destacando-se como pontos positivos a disponibilidade dos ARV, a ausência de medicamentos vencidos e de prescrições em desacordo com o consenso de tratamento para pacientes com HIV/AIDS, bem como a boa orientação dos pacientes no uso dos medicamentos ARV. Como problemas destacaram-se os baixos índices de conformidade em relação a boas práticas de dispensação e armazenamento e um prazo elevado para a distribuição dos medicamentos. Foram também efetuadas análises por componente da assistência farmacêutica, em que apenas o componente distribuição obteve um grau de qualidade aceitável. Considerando-se as dimensões de avaliação disponibilidade de recursos, organização da assistência e qualidade técnica, os resultados mostraram deficiências na dimensão organização da assistência. O resultado individual de cada UDM mostrou que apenas duas possuem grau de qualidade bom, e o resultado geral para a FMS de Niterói foi de 50,3% de atendimento aos critérios de qualidade, considerado apenas regular. Foram sugeridas propostas de ações e intervenções, entre elas, a melhoria nas condições estruturais das farmácias das unidades de saúde do município, e aumento na capacitação dos profissionais envolvidos com a assistência para melhoria dos processos de trabalho
The strengthening of the pharmaceutical services to patients having HIV/AIDS is of major importance to maintain the sustainability mainly for its high implementation and execution costs. On this paper it was performed an evaluation of the pharmaceutical HIV services in the city of Niterói, emphasizing its management. The study aimed to answer two evaluative questions: The structure and existing work processes are suitable for guarantee pharmaceutical services’ quality to people living with HIV (PHVA) in Niterói? The structure and existing work processes are adequate to ensure access to medicines for opportunistic infections and ARV patients to PHVA in Niterói? The evaluation design was a case study, and a normative approach focusing on quality was also used, involving analysis of the structure, process and results, by building a logical theoretical model. Out of the eight existing UDM in the city, six were evaluated in this study. Matrices of relevance and analysis and judgment were created, in which the indicators were divided into four groups according to the components of the pharmaceutical services under the responsibility of the city described in the logical model. The indicators were initially analyzed individually, where as positive points, the availability of ARVs, the absence of expired drugs and prescriptions in disagreement with the consensus of treatment for patients with HIV / AIDS as well as good guide of patients in the use of antiretroviral medications were highlighted. The main problems identified were the low levels of conformity against good practice criteria of dispensing and storage and a high period for the medicine distribution. Pharmaceutical services components were also analyzed and distribution was the only component that obtained an acceptable level of quality. The dimensions availability of resources, organization of services and technical quality were investigated and the organization of services aspect obtained the lowest grade. The individual result of each UDM showed that only two achieved good quality degrees, and the overall result to Niterói’s FMS was 50.3 %, which was considered only regular. Actions and interventions have been suggested, amongst them, the improvement of the structural conditions of pharmacies’ health facilities in the city, and an increase in the training of professionals involved with assistance to improve work processes

Thesis (MBA)--Stellenbosch University, 2004.
ENGLISH ABSTRACT: HIV infection has increased sharply in SA over the past decade, from almost zero to a level where between 4-6 million citizens are estimated to be HIV positive (i.e. around Il percent of the total population). Given the considerable lag and link between the HIV and AIDS epidemic, the mortality consequences of this exponential increase in HIV infection over the 1990s are more or less matter-of-fact over the coming decade; even drastic interventions can do little to avoid this reality, albeit possibly impactingfurther beyond. The health care industry, and more specifically the pharmaceutical industry, is the only industry that can have a direct impact on the outcome of the epidemic in terms of provision of antiretroviral drugs. More importantly, the decision by multinational companies to provide voluntary licensing to local SA pharmaceutical manufacturers for the manufacturing of generic ARVs has gone a long way into achieving the World Health Organisations' objective of providing an ARV cocktail for less than $1,00 per day. The mam aim of the study is to establish and study the micro-economic effect of HIV/AIDS on a South African pharmaceutical manufacturer and to evaluate their HIV/AIDS Policy with the framework of the mV/AIDS & SID Strategie Plan for South Africa 2000-2005. Both qualitative and quantitative methods were used to obtain data from various key informants, manufacturers and market survey companies. The analysis of quantitative data was done using Excel software and a descriptive analysis method was used to interpret the data. The key findings from the study are that Aspen Pharmacare will experience a 20,8 % HIV prevalence rate in 2005, which will progressively increase to a 25,6 % level in 2015. This prevalence level will be severely experienced in the skilled, semi-skilled and unskilled employment of the company during the 2010 period and will start to stabilise in the latter part of 2015. The AIDS prevalence in the company will increase from a 2,0 % level in 2005 to a 4,4 % level in 2015. This increase is largely due to the increase in the prevalence rates in the semi-skilled and unskilled employees. At a senior management level the forecasted number of employees that will have clinical AIDS after 2010 is between 6 and 8. This clearly indicates that mv/AIDS prevalence at this level is independent of race and is lifestyle dependent. If the company were to have the full responsibility for the provision of benefits, based on the current expected employee benefit structures, the direct cost to company would add 10 % to salary and wages by 2005 and around 20 % by 2010. Indirect costs to company, such as recruitment and training, increased labour turnover, lost skills and intellectual property, etc. are estimated to be 2,5 % by 2005 and 5 % by 2010. With the high HIV/AIDS prevalence rates, especially amongst the unemployed, companies will have to carry the costs of their mv/AIDS patients for longer and register then with Aid for AIDS when it becomes too costly. More importantly employers will have to investigate the cost implication of assisting employee dependents, as this will have a direct impact on the morale of the employees. Aspen Pharmacares' mv/AIDS Policy goes beyond the requirements of the mv/AIDS Strategic Plan for SA in terms of the legal and social requirements. The company also has a Corporate Social Investment division that assists many NGOs, clinics, hospitals and communities. Based on the intellectual property, the pharmaceutical competencies and the continuous dialogue that exists between the pharmaceutical industry and the department of health, the researcher concludes, that pharmaceutical companies have an advantage over nonpharmaceutical companies in dealing with the mv/AIDS issues. The paper concludes by suggesting recommendations that companies can adopt to ensure that their mv/AIDS policy can form a significant component of their skills retention strategy.
AFRIKAANSE OPSOMMING: MIV infeksie het skerp gestyg in SA oor die laaste dekade, vanaf amper geen tot 'n vlak waar tussen 4-6 miljoen inwoners beraam word om MIV positiefte wees (minstens 11% van die totale bevolking). Gegee die aansienlike vertraging en skakel tussen die MIV en VIGS epidemie, word die eksponensiële toename in die sterfte syfer as gevolg van MIV infeksies gedurende die jare negentig as vanselfsprekend aanvaar in die komende dekade. Selfs ingrypende veranderinge kan min doen om hierdie katastrofe te keer. Die gesondheidsorg industrie, en meer spesifiek die farmaseutiese industrie is die enigste industrie wat 'n direkte slag kan slaan om die uitkoms van die epidemie te beinvloed, in terme van voorsiening van antiretrovirale medisyne. Die besluit van die multinasionale maatskappye om vrywillige lisensiëring aan plaaslike farmaseutiese maatskappye te bied, vir die vervaardiging van generiese antiretrovirale medisyne, is een stap vorentoe om by die doelwit van die Wereld Gesondheidsorg Organisasie se doelwit van die voorsiening van 'n daaglikse toediening van antiretrovirale medisyne van minder as $1.00 per dag. Die primêre doelwit van hierdie projek is om te bepaal wat die mikro-ekonomiese effek van MIV/VIGS op 'n Suid Afriakaanse farmaseutiese vervaardiger is en hul MIV/VIGS beleid te evalueer binne die raamwerk van die MIV/VIGS en SOS Strategiese Plan vir SA 2000-2005. Beide kwalitatiewe en kwantitatiewe metodes is gebruik om data te verkry vanaf verskeie bronne, vervaardigers en marknavorsings maatskappye. Die kwantitatiewe inligting was geanaliseer deur gebruik te maak van "Excel" sagteware en 'n beskrywende analitiese metode was gebruik om die data te interpreteer. Die hoof bevindinge van die studie is dat Aspen Pharmacare 'n MIV infeksie vlak van 20.8 % in 2005 sal ondervind, wat progressief sal toeneem tot 25,6 % in 2015. Hierdie infeksie vlak sal in die geskoolde, semi-geskoolde en ongeskoolde arbeid die ergste voorkom gedurende die 2010 periode en sal dan stabiliseer in die latere gedeelte van 2015. Die VIGS infeksie vlak in die maatskappy sal toeneem vanaf 2,0 % in 2005 tot 'n 4,4 % in 2015. Hierdie toename kan toegeskryf word aan die toename in die infeksie vlakke van die semi-geskoolde and ongeskoolde arbeid. Op die senior bestuurs vlak word beraam dat tussen 6 en 8 werknemers VIGS onder lede sal hê na 2010. Hierdie beraming toon duidelik aan dat MIV/VIGS op hierdie vlak onafhankilik van kleurgroup is en direk leefstyl verwant is. Gebaseer op die huidige verwagte werknemer voordele struktuur, en die feit dat die maatskappy volle verantwoordelikheid sou aanvaar vir die voorsiening van voordele, word beraam dat die direkte koste as gevolg van MIV/VIGS 'n toename van 10 % in 2005 en 20 % in 2010 by salarisse en lone sal voeg. 'n Toename van 2,5 % in 2005 en 5 % in 2010 word beraam vir indirekte koste (werwing van personeel, opleiding, ens.)as gevolg van MIV/VIGS. Met die hoë MIV/VIGS infeksievlakke, veral onder werkloses, sal maatskappye die kostes vebonde aan hul MIV/VIGS werknemers vir langer moet verduur en dan later sulke werknemers registreer by "Aid for AIDS" indien dit onbekostigbaar word. Belangriker is die feit dat werknemers die koste implikasie bepaal in die verband, omdat dit 'n direkte invloed sal hê op werknemer selfvertroue. Aspen Pharmacare se MIV/VIGS beleid bied meer as die wettige en sosiale vereistes soos uiteengesit in die MIV/VIGS en SOS Strategiese Plan vir SA 2000-2005. Die maatskappy het ook 'n Korporatiewe Maatskaplike Beleggings afdeling wat 'n bydra lewer by NGOs, klinieke,hospitale en gemeenskappe. Gebaseer op die intelligensie eiendom, die farmaseutiese bekwaamheid en die aanhoudende gesprekvoering wat bestaan tussen die farmaseutiese bedryf en die department van gesondheid, oortuig die navorser dat farmaseutiese maatskappye 'n voordeel het bo nie-farmaseutiese maatskappye in die hantering van die MIV/VIGS strydvraag. Hierdie studie sluit af met aanbevelings wat maatskappye kan toepas om te verseker dat hul MIV/VIGS beleid 'n betekenisvolle komponent van hul bekwaanheids retensie strategie is.

In order for a medicinal product to produce a consistent and reliable therapeutic response, it is essential that the final composition of the product is invariable and that the active ingredient/s is/are present in appropriate, non-toxic amounts. However, due to the complexity involved in the standardization of natural products, quality control (QC) criteria and procedures for the registration and market approval of such products are conspicuously absent in most countries around the world. African Potato (AP) is of great medical interest and this particular plant has gained tremendous popularity following the endorsement by the South African Minister of Health as a remedy for HIV/ AIDS patients. Very little information has appeared in the literature to describe methods for the quantitative analysis of hypoxoside, an important component in AP. It has also been claimed that sterols and sterolins present in AP are responsible for its medicinal property but is yet to be proven scientifically. To-date, no QC methods have been reported for the simultaneous quantitative analysis of the combination, β- sitosterol (BSS)/ stigmasterol (STG)/ stigmastanol (STN), purported to be present in preparations containing AP. The effect of concomitant administration of AP and other herbal medicines on the safety and efficacy of conventional medicines has not yet been fully determined. Amongst the objectives of this study was to develop and validate quantitative analytical methods that are suitable for the assay and quality control of plant material, extracts and commercial formulations containing AP. Hypoxoside was isolated from AP and characterized for use as a reference standard for the quality control of AP products and a stability-indicating HPLC/ UV assay method for the quantitative determination of hypoxoside was developed. In addition, a quantitative capillary zone electrophoretic (CZE) method was developed to determine hypoxoside, specifically for its advantages over HPLC. A HPLC method was also developed and validated for the quantitative analysis of BSS, STG and STN in commercially available oral dosage forms containing AP material or extracts thereof. The antioxidant activity of an aqueous extract of lyophilized corms of AP along with hypoxoside and rooperol were investigated. In comparison with the AP extracts and also with hypoxoside, rooperol showed significant antioxidant activity. The capacity of AP, (extracts, formulations, hypoxoside and rooperol as well as sterols to inhibit in vitro metabolism of drug substrates by human cytochrome P450 (CYP) enzymes such as CYP 3A4, 3A5 and CYP19 were investigated. Samples were also assessed for their effect on drug transport proteins such as P-glycoprotein (P-gp). Various extracts of AP, AP formulations, stigmasterol and the norlignans, in particular the aglycone rooperol, exhibited inhibitory effects on CYP 3A4, 3A5 and CYP19 mediated metabolism.These results suggest that concurrent therapy with AP and other medicines, in particular antiretroviral drugs, can have important implications for safety and efficacy. Large discrepancies in marker content between AP products were found. Dissolution testing of AP products was investigated as a QC tool and the results also revealed inconsistencies between different AP products.

En 2010, l'Organisation Mondiale de la Santé (OMS) a publié de nouvelles recommandations pour le traitement contre le Vih/Sida dans le but d'améliorer la qualité des thérapies antirétrovirales (TARV) distribuées dans les pays en voie de développement (PED). Cependant, les coûts de plus en plus importants liés à l'incorporation des antirétroviraux (ARV) de nouvelle génération, associés à l'intensification de la protection des droits de la propriété intellectuelle (DPI), accentuent le déséquilibre entre les priorités d'expansion de la couverture des patients et les objectifs d'amélioration des traitements, ce qui favorise la pérennité d'un double standard de soins dans le monde. Cette thèse a pour objectif d'analyser les déterminants de l'incorporation des nouvelles technologies et de l'évolution des prix des ARV pour mieux comprendre leur impact sur la qualité et l'accessibilité financière des TARV dans les PED. La présente recherche est basée sur la politique brésilienne de TARV et les leçons qu'elle peut apporter dans la lute contre l'épidémie du Vih/Sida. La première partie de la thèse porte sur les critères utilisés pour l'incorporation des nouveaux médicaments dans les protocoles cliniques de TARV. L'étude part des méthodes de l'analyse de contenu et statistique pour examiner l'impact des prix des ARVs sur les recommandations thérapeutiques et comment celles-ci influencent la pratique médicale
In 2010, the World Health Organization (WHO) published new HIV/AIDS treatment recommendations which aim at improving the quality of antiretroviral therapy (ART) delivered in developing countries. Nonetheless, the higher costs of incorporating new and more potent antiretrovirals (ARVs), coupled by the intensification of intellectual property rights (IPRs) protection, put in evidence a growing trade-off between patient coverage expansion priorities and treatment quality objectives, which tend to favor the perpetuation of a double standard of HIV care in the world.This thesis aims at analyzing the determinants of technology incorporation and price evolution in HIV care as the basis for discussing how these can impact both the quality and affordability of ART in low and middle-income settings. The present research takes as reference the Brazilian ART policy and the insights it may provide in the fight against the HIV/AIDS epidemic. The first part of this thesis addresses the criteria used for the incorporation of novel drugs in ART guidelines. Content and statistical analyses are used to examine the impact of ARV prices on therapeutic recommendations and how the latter have been able to influence clinical practice. They show that, although efficacy, toxicity and dosing convenience represent major determinants of ART incorporation decisions in Brazil, costs have most recently started influencing deferral in the use of new ARVs. The second part takes into account the role of patent protection on pharmaceutical innovation and pricing, further employing descriptive and econometric approaches to analyze ARV market structure and prices in Brazil

Background: Medication misuse results in considerable problems for both patient and society. It is a complex problem with many contributing factors, including timely access to product information. less thanbrgreater than less thanbrgreater thanObjective: To investigate the value of 3-dimensional (3D) visualization paired with video conferencing as a tool for pharmaceutical advice over distance in terms of accessibility and ease of use for the advice seeker. less thanbrgreater than less thanbrgreater thanMethods: We created a Web-based communication service called AssistancePlus that allows an advisor to demonstrate the physical handling of a complex pharmaceutical product to an advice seeker with the aid of 3D visualization and audio/video conferencing. AssistancePlus was tested in 2 separate user studies performed in a usability lab, under realistic settings and emulating a real usage situation. In the first study, 10 pharmacy students were assisted by 2 advisors from the Swedish National Co-operation of Pharmacies call centre on the use of an asthma inhaler. The student-advisor interview sessions were filmed on video to qualitatively explore their experience of giving and receiving advice with the aid of 3D visualization. In the second study, 3 advisors from the same call centre instructed 23 participants recruited from the general public on the use of 2 products: (1) an insulin injection pen, and (2) a growth hormone injection syringe. First, participants received advice on one product in an audio-recorded telephone call and for the other product in a video-recorded AssistancePlus session (product order balanced). In conjunction with the AssistancePlus session, participants answered a questionnaire regarding accessibility, perceived expressiveness, and general usefulness of 3D visualization for advice-giving over distance compared with the telephone and were given a short interview focusing on their experience of the 3D features. less thanbrgreater than less thanbrgreater thanResults: In both studies, participants found the AssistancePlus service helpful in providing clear and exact instructions. In the second study, directly comparing AssistancePlus and the telephone, AssistancePlus was judged positively for ease of communication (P = .001), personal contact (P = .001), explanatory power (P andlt;.001), and efficiency (P andlt;.001). Participants in both studies said that they would welcome this type of service as an alternative to the telephone and to face-to-face interaction when a physical meeting is not possible or not convenient. However, although AssistancePlus was considered as easy to use as the telephone, they would choose AssistancePlus over the telephone only when the complexity of the question demanded the higher level of expressiveness it offers. For simpler questions, a simpler service was preferred. less thanbrgreater than less thanbrgreater thanConclusions: 3D visualization paired with video conferencing can be useful for advice-giving over distance, specifically for issues that require a higher level of communicative expressiveness than the telephone can offer. 3D-supported advice-giving can increase the range of issues that can be handled over distance and thus improve access to product information.

Funding Agencies|eHealth Institute by the National Cooperation of Swedish Pharmacies-Apoteket AB, Linnaeus University (previously University of Kalmar)||Regional Council in Kalmar County||Kalmar County Council||Municipality of Kalmar||

Desde a sua descoberta, no início da década de 80, o HIV/aids, constituiu-se como uma doença que ultrapassa os limites da dimensão biomédica, apresentando diversos desafios à sociedade. No Brasil, estima-se que aproximadamente 734 mil pessoas vivem com HIV/aids. Foram desenvolvidas diferentes classes de drogas antirretrovirais para seu tratamento; as quais são eficazes para o controle parcial da replicação viral. Sem a descoberta da cura, é imprescindível que as pessoas vivendo com HIV/aids sigam as recomendações da equipe de saúde, aderindo ao tratamento proposto; aumentando sua qualidade de vida, bem como contribuindo para a diminuição da transmissão do vírus. Durante o tratamento, algumas dificuldades podem surgir, determinando momentos de maior ou menor adesão ao mesmo e os profissionais de saúde, dentre eles, os farmacêuticos, devem estar atentos a estes momentos. Este estudo transversal teve como objetivo analisar a retirada do TARV nos últimos 24 meses e investigar os possíveis fatores que levam a retirada desta medicação de forma irregular na Unidade Especial de Tratamento de Doenças Infecciosas (UETDI) do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo. Participaram 250 pessoas que vivem com HIV/aids que retiram a medicação na Farmácia do local do estudo. Os participantes foram separados em dois grupos: Grupo em Atraso e Grupo Controle segundo seus históricos de dispensação da TARV nos vinte e quatro meses anteriores a realização das entrevistas. Predominaram participantes do sexo masculino (57,6%), com mais de 40 anos (76%), brancos (51,6%), com baixa escolaridade (48,4%), sem parceiro fixo (52,4%), residentes em Ribeirão Preto (63,6%). Todas as variáveis foram relacionadas em um estudo univariado e aquelas com um valor de \"p\" igual ou menor que 0,2 foram selecionadas para análise multivariada. As associações entre variáveis selecionadas e a retirada irregular comparada com a retirada regular, foi estimada pela estimativa com intervalo de confiança de 95%. As variáveis que mostraram associação com a retirada da TARV em atraso foram: fazer uso de outro medicamento além da TARV, apresentar resultado de exame de carga viral como detectável, ter, no início do período analisado, contagem de linfócitos T CD4 menor que 200 células /mm3 e ter baixa adesão como resultado do Teste de Morisky- Green
Since its discovery in the early 80s, HIV / AIDS was established as a disease that pushes the boundaries of biomedical dimension, presenting many challenges to the society. In Brazil, there are almost 734,000 people carrying HIV / AIDS. Different classes of antiretroviral drugs were developed for their treatment, which are effective in partial control of viral replication. Yet incurable disease it is essential that people living with HIV / AIDS follow the recommendations of the health care agents, adhering to the proposed treatment, increasing their quality of life, and contributing to the reduction of transmission of the virus. During treatment, some difficulties may arise, determining moments of greater or lesser adherence, and pharmacists among other health professionals, should be aware of these moments. This cross-sectional study aimed to analyze the withdrawal of ART in the last 24 months, and investigate the possible factors that lead the medication withdrawal erratically on Special Treatment of Infectious Diseases Unit (UETDI) of the Clinics Hospital - School of Medicine of Ribeirao Preto, University of São Paulo. Two hundred and fifty people living with HIV / AIDS got medication in the study site pharmacy. Participants were divided into two groups: Group Control and Group Delay, according to their historical dispensing of ART in twenty-four months prior to the interviews; predominant male participants (57.6%) with more than 40 years (76%), white (51.6%), with low education (48.4%), with no steady partner (52.4%), residents in Ribeirão Preto (63.6%). All variables related in a univariate analysis, and those with a value of \"p\" equal to or smaller than 0.2 were selected for multivariate analysis. The associations between selected variables, and the irregular removal compared to regular withdrawal were estimated with 95% confidence interval. The variables that were associated with the withdrawal of ART arrears, and making use of another drug in addition to HAART, presented results of viral load test as detectable, having the beginning of period analyzed, CD4 lymphocyte count less than 200 cells / mm3, and have low compliance as a result of Morisky- Green test.

With chronicity of AIDS and the increasing number of patients on Antiretroviral Therapy (ART) monitoring of adherence to treatment has become a priority in public health, for maintenance of high rates of adherence depends on the success of treatment. In front of a situation of chronic disease, challenges arise, determining the need for new practices related to adherence monitoring of People Living with HIV/AIDS (PLWHA) and before this context, the Pharmaceutical Care presents itself as an instrument to improve adherence to TARV, since studies show that the Pharmaceutical Care is able to improve adherence. So, the objective was to evaluate the influence of Pharmaceutical Care on adherence to antiretrovirals in PVHA starting treatment in a Dispenser Unit Antiretroviral Drugs (UDM). The longitudinal study has been realized with convenience sampling where included patients starting TARV in naïve patients, were divided into two study groups. The intervention group received Pharmaceutical care and monitoring, while the control group followed the routine care of the service. Adherence to treatment was confirmed by self-report, regular withdrawals of ARV and evolution of viral load. The profile of PLHA included in this study presented social demographic characteristics that follow the national epidemiological trends. Adherence to antiretroviral therapy showed better results in the intervention group. It was found that the highest number of dropouts in the control group occurred when patients given medical follow-up in public health services compared with individuals. The results of the study allowed the development of a protocol for application in Pharmaceutical care routine UDM.
Com a cronicidade da AIDS e o crescente número de pacientes em uso de Terapia Antirretroviral (TARV) a monitorização da adesão ao tratamento se tornou uma das prioridades em saúde pública, pois da manutenção de altas taxas de adesão depende o sucesso do tratamento. Diante do quadro de cronicidade da doença, surgem desafios, determinando a necessidade de novas práticas relacionadas ao monitoramento da adesão das Pessoas Vivendo com HIV/AIDS (PVHA) e diante desse contexto, a Atenção Farmacêutica apresenta-se como um dos instrumentos para melhorar a adesão a TARV, uma vez que estudos mostram que a Atenção Farmacêutica é capaz de melhorar a adesão. Assim, objetivou-se avaliar a influência da Atenção Farmacêutica na adesão aos antirretrovirais em PVHA em início de tratamento em uma Unidade Dispensadora de Medicamentos Antirretrovirais (UDM). Para tal, foi realizado um estudo longitudinal com amostragem por conveniência onde se incluiu pacientes em início de TARV virgens de tratamento, alocados em dois grupos de estudo. O grupo intervenção recebeu Atenção Farmacêutica e acompanhamento, enquanto que, o grupo controle seguiu a rotina de atendimento do serviço. A adesão ao tratamento foi comprovada através de autorrelato, regularidade nas retiradas de ARV e evolução da carga viral. O perfil das PVHA incluídas neste estudo apresentou características sócias demográficas que seguem as tendências epidemiológicas nacionais. A adesão a TARV apresentou melhores resultados no grupo de intervenção. Verificou-se que, o maior número de abandonos no grupo controle ocorreu quando os pacientes recebiam acompanhamento médico nos serviços de saúde público em comparação com os particulares. Os resultados do estudo permitiram o desenvolvimento de um Protocolo de Atenção Farmacêutica para aplicação na rotina da UDM.

For many years pharmaceutical patents and their impact on prices have been at the centre of the international debate over insufficient access to lifesaving HIV/AIDS medicines in developing countries. The conflict has largely revolved around the implementation of an intellectual property system in the developing world, subsequent the adaptation of the TRIPS Agreement, which has made a 20 year pharmaceutical patent protection mandatory for these countries and consequently contributed to high drug prices for patented medicines as well as limited the use of generic drugs.

Developing countries, where patents are already in place, have sought to reduce high drug prices by making use of compulsory licensing, a safeguarding practice allowing the production or importation of a generic medicine without the consent of the patent holder. Compulsory licences are allowed under the TRIPS Agreement, but disagreements about the conditions, under which compulsory licences are available for ‘essential medicines’, have restricted their use. A definition of the extent to which compulsory licensees can export generic drugs to developing countries unable to manufacture their own has been missing, but on 30 August 2003 the WTO announced that it had resolved this problem by lifting the TRIPS Agreement’s restrictions on exports and permitting exports of drugs produced under a compulsory license as an exception to a patent right. The main question is whether the compulsory licensing system as prescribed in the recent Decision is an ample means of improving access to patented AIDS medicines in the developing world.

By means of legal and economic reasoning this master thesis argues that the 30 August Decision on lifting TRIPS’ restrictions on exports of patented pharmaceuticals produced under compulsory licences provides complex and uncertain rules, rendering an unreliable employment of compulsory licensing. It is desirable that further recommendations are given on which generic producing companies should be awarded compulsory licences and also on which premises. In reality, the debate about compulsory licensing is part of a much wider structural problem in development policy. The solution to the inaccessibility problem requires a mix of courses of action with a functioning compulsory licensing system included. However, disagreements such as how necessary funding should be divided equitably between developed countries could protract the reaching of a pragmatic solution.

The chemokine receptor CCR5 (CCR5) plays an integral role within the inflammatory network of cells. Importantly, CCR5 is a mediator in several disease states and can be targeted using small molecule antagonists. Within this work, CCR5’s role in prostate cancer and HIV/AIDS has been exploited in order to develop potential therapeutics and probes. First, a series of novel compounds was designed by using pharmacophore-based drug design based upon known CCR5 antagonists and molecular modeling studies of the CCR5 receptor’s three-dimensional conformation. Once synthesized, these compounds were tested for their CCR5 antagonism and their anti-proliferative effects in several prostate cancer cell lines. The data from both the calcium mobilization studies and the anti-proliferation studies suggests that the compounds synthesized have activity as CCR5 antagonists and as anti-proliferative agents in certain prostate cancer cell lines. In addition, a bivalent ligand containing both a mu opioid receptor (MOR) and a CCR5 antagonist pharmacophore was designed and synthesized in order to study the pharmacological profile of the putative CCR5-MOR heterodimer and its relation with NeuroAIDS. The structural-activity relationship between the bivalent ligand and the heterodimer was studied with radio-ligand binding assays, functional assays, HIV-1 fusion assays, cell fusion assays, and in silico molecular dynamics. The subsequent bivalent ligand was proven to be a potent inhibitor in both an artificial cell fusion assay mimicking HIV invasion and a native HIV-1 invasion assay using live virus. In all, two novel sets of compounds were synthesized that targeted either CCR5 or the CCR5-MOR heterodimer. For the CCR5 antagonists, as leads for prostate cancer therapeutics, further work needs to be done to ascertain and develop their structure-activity-relationship. This library of novel compounds was shown as promising leads as CCR5 and anti-prostate cancer agents. The bivalent ligand targeting the CCR5-MOR heterodimer proved to be a potent and tissue-specific inhibitor for neuroAIDS where the known treatment, maraviroc, is less efficacious and fails to inhibit virus entry in the presence of morphine. Both projects illustrate the roles that CCR5 plays in these two unique diseases.

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

Introdução: A infecção pelo HIV está sendo considerada de caráter crônico e potencialmente controlável desde a instituição da Terapia Antirretroviral (TARV) e disponibilidade de marcadores para acompanhamento da sua evolução. A adesão ao tratamento necessária para garantir a supressão virológica é elevada, necessitando de monitoramento adequado a fim de detectar potenciais pacientes não-aderentes e auxiliar nas intervenções. O uso dos registros de dispensação de medicamentos pode ser uma estratégia simples e factível para identificar potenciais pacientes não-aderentes. Intervenções do profissional farmacêutico podem contribuir para aumentar a adesão e obter desfechos clínicos favoráveis. Objetivos: O objetivo deste estudo é avaliar se os registros de dispensação de medicamentos e intervenções farmacêuticas podem contribuir na avaliação e melhora da adesão ao tratamento antirretroviral e outros desfechos clínicos relevantes, através de duas revisões sistemáticas. Métodos: Foram realizadas duas revisões sistemáticas, com busca nas bases de dados MEDLINE, Registro de ensaios clínicos da Cochrane, EMBASE, IBECS, CINAHL, IPA, SCOPUS, Web Of Science, LILACS, Scielo e Clinical Trials. Para avaliar os registros de dispensação na adesão ao tratamento foram selecionados estudos que estimaram a adesão ao tratamento pelos registros de dispensação de antirretrovirais e compararam com desfechos clínicos (carga viral, contagem de linfócitos CD4, resistência viral ou óbito) ou outro método para estimar a adesão. Para avaliar intervenções farmacêuticas na TARV foram selecionados ensaios clínicos randomizados em que havia a participação de farmacêutico na intervenção profissional, e as principais medidas de desfecho selecionadas foram a adesão ao tratamento, carga viral e CD4. Resultados: Foram encontrados 3551 estudos para a primeira revisão, dos quais 92 foram selecionados. Os estudos selecionados eram heterogêneos, sendo estudos de coorte os mais frequentes, o período mais utilizado para cálculo da adesão de seis meses e o ponto de corte mais utilizado para adesão de 95%. Os resultados dos estudos apontam para associação positiva entre adesão estimada pelos dados de farmácia e carga viral e outros métodos, com melhores resultados desta associação quando avaliada de forma temporal. Para a revisão sobre atenção farmacêutica na TARV foram encontrados 681 estudos, dos quais quatro atenderam aos critérios de inclusão. A adesão ao tratamento foi estimada em todos os estudos, e o odds ratio sumarizado foi de 1,47 (IC95% 0,81 – 2,65). A supressão virológica foi estimada em três estudos, obtendo odds ratio sumarizado de 1,95 (IC95% 0,61 – 6,25). Conclusões: Os resultados dos estudos indicam que os dados da farmácia podem ser úteis na avaliação da adesão ao tratamento, relacionando-se com desfechos clínicos como carga viral e CD4. Os resultados das meta-análises sugerem que a intervenção farmacêutica pode auxiliar na melhora da adesão ao tratamento antirreroviral e carga viral, no entanto, não houve diferença estatisticamente significativa entre os grupos. Em populações com baixa adesão e maior vulnerabilidade, a intervenção farmacêutica pode ser mais eficaz.
Introduction: HIV infection is being considered chronic and potentially manageable since the introduction of Antiretroviral Therapy (ART) and availability of biogical markers for monitoring its evolution. Adherence to treatment necessary to ensure virologic suppression is high, requiring adequate monitoring to detect potential nonadherent patients and plan interventions. The use of medication dispensing records can be a simple and feasible method to identify potential non-adherent patients. Pharmacist interventions can increase adherence and get favorable outcomes. Objectives: The aim of this study is to evaluate whether the dispensing drugs records and pharmaceutical interventions may help in assessing and improving adherence to antiretroviral treatment and other relevant clinical outcomes through two systematic reviews. Methods: Two systematic reviews were performed, with the search strategies performed in MEDLINE, Cochrane registration of clinical trials, EMBASE, IBECS, CINAHL, IPA, SCOPUS, Web of Science, LILACS, SciELO and Clinical Trials database. To evaluate the prescription refill records treatment adherence, were selected studies that had measures treatment adherence by records of antiretrovirals dispensing and compared with clinical outcomes (viral load, CD4 count, viral resistance or death) or alternative method to estimate adherence. To evaluate pharmaceutical interventions on ART, randomized clinical trials in which there was participation of pharmacists in the intervention were selected, and the main outcome measures were treatment adherence, viral load and CD4. Results: 3551 studies were found for the first review, of which 92 were selected. The selected studies were heterogeneous, with cohort studies the most frequent, the period most frequent used to calculate adherence were six months and the cutoff for adherence were 95%. Study results indicate good relationship between adherence estimated by pharmacy data, viral load and other methods, with best results of the association between adherence and viral load as measured temporally. For the review of pharmaceutical care in ART 681 studies were found, of which four met the inclusion criteria. Adherence to treatment was estimated in all studies, and summarized odds ratio was 1.47 (95% CI 0.81 to 2.65). Virological suppression was estimated in three studies, getting summarized odds ratio of 1.95 (95% CI 0.61 to 6.25). Conclusions: The study results indicate that the pharmacy claim data can be useful in assessing adherence to antirretroviral treatment, correlating with clinical outcomes such as viral load and CD4. The results of the meta-analyzes suggest that there was no difference between treatment adherence and virologic suppression in intervention group with pharmacist and the control group, despite overall results being favorable to pharmaceutical intervention. In populations with low compliance and vulnerability, pharmaceutical interventions may be more effective.

"Zimbabwe and South Africa are facing an HIV/AIDS epidemic of such proportions that the populations of these countries will markedly decline in the next ten years despite the existence of effective drugs to treat the symptoms of AIDS and dramatically lower the communicability of the virus. These drugs are under patent protection by companies in the developed world and the patents raise the prices above the level of affordability for HIV infected persons in South Africa and Zimbabwe. Zimbabwe has declared a national emergency on HIV/AIDS, apparently in conformance with TRIPS and has issued compulsory licenses to a local company that has started to manufacture and sell cheap anti-retroviral drugs. South Africa has not declared a national emergency and has not invoked the TRIPS flexibilities or utilized flexibilities inherent in its own legislation. However, while thousands of people die every week in the two countries, neither government has yet provided an effective HIV/AIDS policy. Extensive litigation and public pressure in South Africa has led the government to announce a policy of supplying free HIV drugs in public hospitals while the Zimbabwean government has announced the provision of the same drugs, also in public hospitals, apparently utilising the state of emergency. The TRIPS agreement under which the two governments undertook to protect international patents allows compulsory licensing under certain circumstances (not limited to a national emergency) and the Doha Declaration on TRIPS and Public Health, and subsequent agreements by the Ministerial Council of the WTO allow the manufacture and, in limited circumstances, the parallel importation of generic drugs. These provisions provide a theoretical mechanism for poor countries to ensure their citizens' rights of access to health (care). The research is aimed at identifying the extent of the effectiveness of the legal norms created by Articles 20 and 31 of TRIPS, the Doha Declaration and subsequent Council of Ministers' decisions, which together ostensibly provide a framework to allow provision of generic drugs. It is further aimed at investigating how the state of emergency in Zimbabwe has been utilised to provide cheap generic drugs to Zimbabweans and whether this would be an option for South Africa. A comparison of the legal provisions governing the provision of drugs in the two countries will also be undertaken to examine the extent to which international and national constitutional and legal provisions may be utilised to give effect to the right to health." -- Introduction.
Thesis (LLM (Human Rights and Democratisation in Africa)) -- University of Pretoria, 2004.
Prepared under the supervision of Dr. Enid Hill at the American University in Cairo.
http://www.chr.up.ac.za/academic_pro/llm1/dissertations.html
Centre for Human Rights
LLM

Orientadores: Priscila Gava Mazzola, Patricia Moriel
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Muitos fatores contribuem para a resposta do paciente à terapia antirretroviral (TARV), incluindo adesão, efetividade farmacológica e tolerância. A TARV é complexa e longa, e o risco de falha virológica, comumente associada à resistência antirretroviral, aumenta quando a adesão diminui. Neste contexto, a presença do farmacêutico, como o profissional capaz de orientar o paciente em relação à terapia medicamentosa e realizar o acompanhamento farmacoterapêutico, estimula os pacientes a estarem familiarizados com seus próprios esquemas terapêuticos, tornando mais simples a compreensão da importância do uso correto do medicamento, aumentando a adesão à terapia, efetividade e tolerância. Este trabalho teve como objetivo avaliar a efetividade da Intervenção Farmacêutica (IF) na resolução dos Problemas Farmacoterapêuticos (PFTs) e na melhora dos parâmetros clínicos dos pacientes com HIV/AIDS. Foi realizado um estudo prospectivo controlado intervencionista, com amostra consecutiva e de conveniência com controles de reposição emparelhados segundo gênero e valores iniciais de linfócitos T CD4+. Do total de pacientes selecionados para o estudo (n=143), 57 (39,86%) pacientes foram descontinuados e 86 pacientes finalizaram o estudo de 1 ano, sendo 43 pacientes do controle (GC) e 43 do grupo intervenção (GI). Os pacientes do GI receberam acompanhamento farmacoterapêutico por meio de método próprio baseado no método Pharmacotherapy workup. Durante o período de 1 ano foram realizadas 202 Intervenções ou Orientações Farmacêuticas no GI, com uma redução de 38,43% (p=0,0001) do total de PFTs. O GI apresentou aumento médio da variação de CD4 1,84 vezes maior que o aumento observado GC, com média de 154,66 para o GI e 83,80 para o GC. Apesar da carga viral média final do GI ser maior do que aquela observada no GC (17394,51 e 12921,53 cópias/mL, respectivamente), para o GI foi observada uma redução 3 vezes maior da carga viral do que para o GC: GI variou em média 23517,67 e GC, 6226,51. Os resultados deste estudo indicam que as Intervenções Farmacêuticas proporcionaram redução PFTs principalmente aqueles relacionados às reações adversas e interações medicamentosas, promoveram a adesão, aumentaram a efetividade da terapia antirretroviral, constatada com maior elevação da contagem de CD4 e redução da carga viral em comparação com o grupo controle
Abstract: Many factors contribute to the patient's response to antiretroviral therapy (ARVT), including adhesion, drug effectiveness and tolerance. Antiretroviral therapy is complex and lengthy, and the risk of virologic failure commonly associated with antiretroviral resistance increases when adhesion decreases. In this context, the presence of the pharmacist as a professional capable of guiding the patient in relation to drug therapy and follow up drug use, encourages patients to be familiar with their own therapeutic regimens, making it easier to understand the importance of using correct medicine, increasing adherence to therapy, effectiveness and tolerance. This study aimed to evaluate the effectiveness of pharmaceutical intervention (PI) in solving drug related problems (DRPs) and improvement of HIV/ AIDS patients clinical parameters. We conducted a prospective controlled intervention study, with a consecutive and convenience sampling with replaced controls paired by gender and initial T CD4+ lymphocytes values. Out of the total patients enrolled in the study (n=143), 57 (39,86%) patients were discontinued and 86 patients completed the 1-year study, with 43 patients in the control group (CG) and 43 in the intervention group (IG). Patients from de IG received pharmacotherapeutic follow up through a method developed in this work and some Pharmacotherapy workup method features. Over the period of 1 year were performed 202 interventions or counselling on Pharmaceutical IG, with a decrease of 38.43% (p = 0.0001) of total PFTs. The IG showed a mean improvement variation of 1.84 times CD4 greater than the increase observed CG with an average of 154.66 for IG and 83.80 for CG. Although the final viral load mean of IG found were greater than that observed in the CG (17394.51 and 12921.53 copies / mL, respectively), IG presented a reduction of three times greater than that in the CG: IG had mean range of 23517.67 and CG, 6226.51. The results of this study indicate that pharmacist interventions led to lower DRPs especially those related to adverse reactions and drug interactions, promoted adherence, increased the effectiveness of antiretroviral therapy, verified with greater elevation of CD4 count and viral load reduction compared with the control group
Mestrado
Ciencias Biomedicas
Mestra em Ciências Médicas

A Síndrome da Imunodeficiência Adquirida (AIDS) é uma doença de amplo espectro de manifestações, sendo razão de preocupação para qualquer autoridade sanitária. A terapêutica da AIDS é complexa sendo utilizados vários medicamentos, diversas vezes ao dia. Deste modo, objetivou-se o desenvolvimento de formas farmacêuticas sólidas como comprimidos tamponados mastigáveis (CTM), comprimidos com revestimento gastro-resistentes (CRGR) e pellets (PEL) para a veiculação de didanosina (ddl). Seis especialidades farmacêuticas na forma de CTM foram estudadas quanto ao perfil de dissolução, pH do meio e capacidade neutralizante ácida (CNA). Formulações teste de CTM foram propostas visando obter CNAs e perfis de dissolução adequados. Também foram testadas formulações de comprimidos e de pellets para posterior revestimento com filme gastro-resistente derivado do ácido metacrílico. Os ensaios de dissolução das amostras de CTM revelaram diferenças nas características de liberação do fármaco. Também foram observadas diferenças relacionadas a CNA. As formulações de CTM propostas apresentaram, na maioria dos casos, adequados perfis de dissolução e CNA. As formulações CRGR que receberam revestimento gastro-resistente apresentaram perfis de dissolução de ddl adequados, entretanto os comprimidos testados intumesceram em meio ácido, indicando descontinuidade do filme polimérico sobre os comprimidos. Testes para a produção de pellets veiculando ddl mostraram-se adequados quanto à morfologia e dissolução do fármaco, o mesmo sendo observado após o revestimento com filme gastro-resistente.
The Acquired Immune Deficiency Syndrome (AIDS) is a disease that manifests itself in a myriad of ways. Because of this, the condition has been subject of concern to all sanitary authorities. The treatment of AIDS is complex and many types of medicine are used, many times a day. The objective of the present study was to develop solid pharmaceutical dosage forms such as buffered chewable tablets (CTM), gastro-resistant coating tablets (CRGR) and pellets (PEL) for the loading of didanosine (ddl). Six pharmaceutical specialties in the form of CTM were studied so as to identify the profile of the dissolution, the pH of the environment, and the neutralizing acid capacity (CNA). The use of CTM tests formulations was proposed with the objective of obtaining adequate CNA and dissolution profiles. Different compositions of tablets and pellets were tested for a later addition of gastro-resistant film derived from the methacrylic acid. The experiments on the dissolution of the sample of CTM showed differences in the characteristic of the release of the substance. Differences related to the CNA were also observed. The formulations of the CTM proposed showed to have, in the most number of the cases, both adequate dissolution behavior and CNA. The formulations of the CRGR that had received the gastro-resistant coating showed adequate profile of ddl dissolution; the tested tablets, however, swelled in the acid environment, therefore indicating a lack of continuity of the polymeric film over the tablets. The tests for the production of pellets showed adequate results as to its morphology and dissolution of ddl. The same was observed after coating the pellets with gastro-resistant film.

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

En 2015, Epicentre, un centre de recherche épidémiologique crée en 1987 par l'ONG humanitaire Médecins Sans Frontières (MSF) se lance dans un essai clinique randomisé sur un nouveau vaccin contre les formes sévères de diarrhées des enfants de moins de cinq ans. Il est produit par le Serum Institute Of India Limited (entreprise pharmaceutique indienne). L'essai est conduit à Madarounfa, une localité rurale située dans le Sud du Niger. Cette thèse propose de discuter des dimensions globales et des enjeux locaux autour d'un vaccin, le Rotasiil que l'on peut définir comme « un vaccin africain » si l'on tient compte de la façon dont il est présenté et promu par le Serum Institute, MSF et Epicentre. Cet essai vaccinal sur le Rotasiil témoigne de l'utopie des acteurs de la santé globale qui veut que la technologie et la toute-puissance de la médecine puisse venir à bout des maladies en occultant le contexte de violence structurelle dans lequel leur intervention prend place (Farmer 2002; Farmer 2002; Galtung and Hoivik 1971). Il témoigne également de l'émergence de nouveaux acteurs (ONG et industries) dans le champ des politiques de santé mondiale. Cette thèse s'intéresse également à la science « en train de se faire » et analyse les conditions sociales de collecte des échantillons, de leur analyse au laboratoire jusqu'à l'inscription des résultats dans une base de données. Elle décrit également les ajustements et les négociations à l'œuvre dans l'application des « gold standard » des essais cliniques qui se heurtent au contexte interactionnel de leur mise en œuvre (Brives, Le Marcis, and Sanabria 2016)
In 2015, Epicentre, an epidemiological research center created in 1987 by the humanitarian NGO Médecins Sans Frontières (MSF), will begin a randomised clinical trial of a new vaccine against severe forms of diarrhoea in children under five years of age. It is produced by the Serum Institute Of lndia Limited (an Indian pharmaceutical company). The trial is being conducted in Madarounfa, a rural community in southem Niger. This thesis proposes to discuss the global dimensions and local issues surrounding a vaccine, Rotasiil which can be defined as "an African vaccine" if on considers the way it is presented and promoted by the Serwn Institute, MSF, and Epicentre. The Rotasiil vaccine trial is testament to the utopia of global health actors that technology and the omnipotence of medicine can defeat disease b obscuring the context of structural violence in which their intervention takes place (Farmer 2002; Farmer 2002; Galtun · and Hôivik 1971). It also testifies to the emergence of new actors (NGOs and industries) in the field of global healt policies (Bertho-Huidal 2012). This thesis is also interested in the science "in the making" and analyses the social conditions of sample collection, from their analysis in the laboratory to the entry of the results in a database. It ais describes the adjustrnents and negotiations at work in the application of the "gold standard" of clinical trials that are confronted with the interactional context of their implementation (Brives, Le Marcis, and Sanabria 2016)

L'évaluation des bénéfices et des risques des médicaments joue un rôle central dans la protection de la santé publique. Cependant, et de l’avis général, il apparaît que cette évaluation nécessite d’être revisitée. En 2010, aucun examen n’avait encore été effectué pour déterminer si les méthodes disponibles pouvaient être appliquées à l’évaluation de la balance bénéfice-risque des médicaments dans le cadre réglementaire, et si oui à quel point elles seraient applicable. L’objectif de cette thèse a donc été d’identifier la ou les méthodes pouvant être théoriquement utilisées pour ce type d’évaluation, puis de les confronter à des cas concrets afin d’en déterminer leur applicabilité. Les résultats de l’évaluation des méthodes ont montrés que les méthodes les plus appropriées sont la méthode d’aide à la décision multicritère (MCDA) ainsi que ses variantes. Les résultats de l'application pratique de la méthode MCDA ont indiqué que cette méthode peut être utilisé dans les scénarios communs d'enregistrement en Europe. Cependant il convient de noter que cette méthode ne fournit ni une recette « prête à l'emploi » pour exécuter cette évaluation ni une réponse directe
The benefit-risk evaluation of new medicines plays a central role in safeguarding public health. Nevertheless, it seems that the benefit-risk evaluation calls for further improvement. In 2010, no review had been performed of how available benefit-risk assessment methods could be applied for a regulatory benefit-risk assessment and how feasible that would be when facing real-life cases. The objective of this thesis has thus been to identify method(s) that could be theoretically used for such an assessment, and then to confront it/them to real-life cases, in order to determine their applicability. The results of the methods evaluation showed that the most suitable methods for a regulatory benefit-risk assessment of medicinal products are the MCDA method and the MCDA based methods. The results of the practical application of the MCDA indicated that the method could be used for medicinal products registered through a common registration scenario in Europe. However it should be noted that this method provides neither a “ready-made” recipe to perform an assessment nor a direct answer

Dans les pays en développement (PED), les problèmes engendrés par le VIH/SIDA et l’inaccessibilité des antirétroviraux (ARV) s’avèrent être la cause de ravages extrêmement préoccupants à tous les niveaux (démographique, politique, social et économique). Dans le cadre de l’Organisation mondiale du commerce (OMC), et notamment de l’Accord sur les aspects des droits de propriété intellectuelle qui touchent au commerce (« Accord sur les ADPIC »), un nombre croissant de PED ont ou sont en train d’intégrer un standard international de protection des brevets de produits et de procédés pharmaceutiques à leur législation nationale. Cette intégration a eu et continue de jouer un rôle majeur dans la problématique de l’accès aux médicaments dans les PED. Les conditions et les effets du régime de protection des innovations suscitent de vifs débats entre les partisans d’une protection accrue des brevets et les défenseurs de l’accès aux médicaments essentiels. Une des principales motivations de notre travail de recherche est de fournir une étude permettant de trouver des solutions à la fois favorables à l’amélioration de l’accès aux médicaments et à la préservation de l’innovation. Le problème complexe de l’accès aux médicaments ARV dans les PED est influencé par la pluridisciplinarité et l’interdépendance de nombreux facteurs. Le système des brevets ne constitue pas « l’unique » solution au problème. Toutefois, il doit être plus sérieusement considéré dans sa fonction d’équilibrage entre l’intérêt privé et l’intérêt collectif. C’est un outil juridique précieux pour le développement économique et technologique des PED et la réalisation de l’intérêt commun contre la pandémie
In developing countries, problems brought about by HIV/AIDS and inaccessibility of antiretrovirals (ARVs) are proving to be the cause of serious damages at all levels (demographic, political, social and economic). Within the context of the World Trade Organization, and in particular the Agreement on Trade-Related Aspects of Intellectual Property Rights (“TRIPS Agreement”), a growing number of developing countries have integrated or are in the process of integrating into their national law an international standard of patent protection for pharmaceutical products and processes. Such integration continues to play a major role in the issue of access to medicines in developing countries. The conditions and effects of the protection regime respecting innovations give rise to heated debates between supporters of an increased patent protection and defenders of the access to essential medicines. One of the main motivations for our research is to provide a study that helps to find solutions that are both in favour of improving access to medicines and protecting innovation. The complex problem of access to ARV drugs in developing countries is influenced by the multidisciplinarity and interdependence of many factors. The patent system does not solve the problem on its own. However, it should be seriously considered in its function of balancing the private and collective interests. It is a valuable legal tool for the economic and technological development of the developing countries and to achieve the common interest against the pandemic

The Acquired Immune Deficiency Syndrome (AIDS) caused by the human immunodeficiency virus (HIV) represents one of the biggest challenges facing today's globalized world. Meanwhile, transnational drug companies have strengthened their market positions in developing countries as a result of the Agreement on Trade-Related Aspects of Intellectual Property (or TRIPS). Patent protection provided by TRIPS has led to higher prices and reduced access to essential medicines. Low- and middle-income countries are under increased pressure to provide expensive life-saving medicines to their citizens. Brazil's AIDS program is deemed successful in reducing morbidity and mortality rates through universal provision of free AIDS medicines. The program's sustainability came under threat as the result of TRIPS, pressures by transnational corporations, and trade threats by the US government. The research question that drove my dissertation centered on the impact of these threats on policy space available to Brazilian government to sustain its universal social program. How has the incorporation of patent protections for drugs affected the ability of local firms to develop pharmaceutical technology and challenged states like Brazil to fulfill social democratic obligations? Under what conditions can a developing country challenge the interests of transnational drug companies? I employed mixed methods for gathering and analyzing data. These included ethnographic field techniques, content analysis, and archival research. My findings are threefold. First, TRIPS has increased the power of foreign firms to secure monopoly positions in Brazil’s drug markets and weakened Brazil's labs to quickly make generic copies of essential medicines. Second, policy space, though curtailed due to external pressures and treaty obligations, expanded through the development of symbolic power, or what I call "reputational dividends," based on a successful social program. Third, by adroitly marketing its banner AIDS program by employing human rights principles, health officials constructed a triple alliance between the state, local private drug manufacturers, and domestic activists tied into transnational advocacy networks. I employ institutional and power analyses to examine the changing sources of power for transnational capital, social movements, and state actors, as well as analyze the impact patent protection has on the ability of Brazilian firms to produce medicines locally. I posit that globalization results in the formation of strong domestic coalitions who are capable of exploiting the "reputational dividends" of a successful social program in order to contest transnational corporate power. This symbolic form of power appears particularly well-disposed for "middle-income" countries that lack the material forms of power held by a global hegemon or transnational corporations.
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The average life expectancy has been increasing due to aspects such as the advances in medicine and technology. An older population leads to the appearance of several chronic pathologies regarding polymedication, and the outcomes highly depend on patients’ adherence to treatment. This is one of the most determining factors in cure, stabilization, or regression of the disease. The purpose of this project is to highlight the principal failures in the patient journey, from medical appointment to the treatment itself, and to analyze the pharmacist’s role as an adherence promoter. In order to understand the gaps, interviews were made to the three main actors in the patient journey (physician, pharmacist, and patient). This study supports the implementation of a new service in a local community pharmacy of Abrantes. Throughout the interviews it was possible to infer the main adherence to therapy failures, such as the lack of cooperation between healthcare professionals, a non-existent patient-oriented follow-up, and a communication gap between the three main groups. This project also aimed to overcome the obstacles in the patient journey and to increase adherence to therapy by launching a medication management service for patients – Dose Administration Aids (DAA). Thus, to understand the service's feasibility, it was observed the implementation of DAA in a community pharmacy in Abrantes. Despite claiming some requirements, it was possible to conclude the service benefits both customers and pharmacy.
A esperança média de vida da população tem vindo a aumentar devido a aspetos como o desenvolvimento tecnológico na medicina. Este envelhecimento da população conduziu ao aparecimento de diversas patologias crónicas às quais estão associadas a polimedicação. O tratamento só é eficaz se houver adesão à terapêutica, considerada um fator-chave para a cura, estabilização ou regressão de uma doença. O propósito deste projeto é destacar as principais falhas que ocorrem na jornada do doente, desde a consulta até à toma da medicação, avaliando também o papel do farmacêutico na promoção à adesão terapêutica. Para identificar as lacunas neste processo, foram realizadas entrevistas aos três principais grupos, com intervenção direta ou indireta na adesão à terapêutica por parte do doente. Este estudo serve de base à criação de um novo serviço numa farmácia de Abrantes. Ao longo das entrevistas aos três grupos já referidos, foi possível inferir as principais falhas na adesão à terapêutica, das quais se destacam a falta de cooperação entre os profissionais de saúde, a não existência de um acompanhamento personalizado ao doente e uma lacuna na comunicação entre os intervenientes. Não obstante, este projeto ambiciona colmatar estas falhas e aumentar a adesão à terapêutica, propondo um serviço farmacêutico que garante a gestão da medicação aos doentes – Preparação Individualizada da Medicação (PIM). De modo a perceber a sua viabilidade, foi observada a implementação do PIM numa farmácia comunitária em Abrantes, que permitiu concluir que apesar de reivindicar alguns requisitos, o serviço é vantajoso tanto para o cliente como para a farmácia.

Increasing attention has been paid to decentralized health care systems in order to evaluate health outcomes. In Brazil, state-run pharmaceutical assistance falls within the scope of a decentralized health care system, also known as SUS (Brazilian Unified Health System). The research intends to shed light on pharmaceutical policy implementation in Brazil through SUS, and argues that it can be used as a guide for institutional reform. This will be accomplished by reviewing the weaknesses and strengths of the SUS decentralized structure as revealed in the pharmaceutical policy responses to HIV/AIDS and tuberculosis. Under the assumption of pharmaceutical assistance improvement conditioned to re-centralization of some functions; it can be argued that a balanced approach to decentralization is more desirable to the pharmaceutical sector than the existing decentralized system. The aim of this study is to highlight the advantages of establishing a hybrid system for pharmaceutical assistance.

Statement of the issue: Facing large HIV-infected populations, Sub-Saharan African countries are producing antiretroviral (ARV) drugs under provisions of the World Trade Organization’s Agreement on the Trade-Related Aspects of Intellectual Property (TRIPS). Article 7 states that the protection of intellectual property should increase technology transfer to developing countries. This clause and the debate over domestic manufacturers’ ability to provide low-cost ARVs need examination. Methods: Case studies from ARV manufacturing initiatives in Tanzania and South Africa analyzed conditions affecting two outcomes: the type of technology transfer arrangement entered (voluntary license or imitation) and the affordability of ARVs. Data were collected and analyzed from documents, key-informant interviews, and observation. Chi-squared and phi correlation statistics were then conducted across developing countries to test the association of voluntary ARV licensure with TRIPS-compliant patents and domestic firm ownership (state or private). Results: Tanzania’s weak patent system and poorly-financed, partially state-owned firm dissuaded industry investment, but attracted a non-government organization to transfer technology through imitation. Donor-financed ARV tenders, however, restrict competition to international quality-accredited products not produced by the firm. Without large volumes and manufacturing capacity, it cannot achieve economies of scale to reduce prices below imported ARVs. In South Africa, civil society challenged the strong patent system and poor government commitment that inhibited an ARV rollout. This and a well-financed, publicly-traded firm leveraged voluntary licenses. With international quality approval, the firm increased first-line ARV affordability; however, limited domestic competition keeps treatment prices above those of neighbouring countries. A multi-country analysis found 321 generic ARV manufacturing initiatives in 86 firms across 25 developing countries. Voluntary ARV licenses had a strong positive association with TRIPS-patent compliance (ф=.56, p<.0001) and a weak negative association with state-ownership (ф=.19, p<.0001). Firms in South Africa and India were granted 77% of licenses and accounted for most quality accredited generic ARVs. Conclusion: Despite positive association, technology transfer does not readily result from patent protection, particularly to state-owned firms. Developing countries must enact policies to enable affordable ARVs; yet, they must be cautious using local production to increase ARV access, as most initiatives cannot compete with high-volume generic manufacturers.

The HIV-1 pandemic affects millions of people worldwide with approximately 70% of those affected residing in sub-Saharan Africa (SSA) relying on traditional medicines for treatment. The key aim of the study was to isolate and characterise an active phyto-pharmaceutical ingredient (API) from L. trigonus for use as a vaginal microbicide. The aerial parts of L. trigonus were oven-dried at 80°C, ground and then extracted with boiling water for 30 minutes. Aqueous extracts were screened using an HIV-1 neutralization assay in TZM bl cells. Chromatographic and spectroscopic techniques were used to purify, isolate and identify the API. The API (BP36-117-26464C) was identified as a polymeric macromolecule with IC50 = 0.04 μg/ml against HIV-1 HXB 2 subtype B. This activity is comparable to the ARV drug, enfuvirtide (IC50 = 0.02 μg/ml). The API consists of galacturonic acid polymer and a mixture of seven compounds. Its mode of action may involve inhibiting virus attachment. The activity of this precipitate (BP36-117-26464C) tested against HIV-1 subtype C pseudovirions and shown to compare favorably with that of enfuvirtide (T20). The water-soluble nature of this API and its mode of action identified it as a potential microbicide. In the current form, the precipitate (API) would be difficult to develop as an oral treatment for HIV, as high-molecular weight agents often have poor bioavailability following oral administration. However, large molecules with potent anti-HIV activity are ideal for topical use and potent development as a microbicide.
Life & Consumer Sciences
M.Sc (Life Sciences)

Orientação: Nuno Almeida Saraiva
O sucesso da terapia anti-retroviral (ART) na manutenção da infeção pelo HIV tem sido um dos melhores neste último século. A ART levou à transformação do HIV, de uma sentença universal de morte para uma doença crónica. Em todas as partes do mundo, assistimos a uma redução dramática na morbilidade e mortalidade relacionadas com o HIV, e o tratamento está agora disponível para cerca de 21 milhões de indivíduos – mais de metade do número de pessoas que vivem com este vírus. No entanto, apesar desses grandes avanços, mais de um milhão de pessoas morrem a cada ano de doenças relacionadas com o HIV, e há registo de cerca 1,8 milhão de novas infeções. Contudo, permanecem por resolver dois grandes desafios científicos para realmente ver o fim do HIV – encontrar uma cura e uma vacina eficaz. Investigações realizadas na última década resultaram numa melhor compreensão de como e onde o HIV persiste em pacientes a realizar ART. Ficou claro que, o estabelecimento de uma infeção latente em células de vida longa é a principal barreira para curar o HIV ou para permitir uma remissão sustentada livre de ART. Baseadas por estudos in vitro e ex vivo, várias abordagens terapêuticas destinadas a esgotar o pool de células infetadas de forma latente, foram testadas em ensaios clínicos experimentais de pequena escala, incluindo estudos de intensificação de ART, na edição de genoma, na ART durante a infeção precoce e aguda, e na reversão de latência. Mais recentemente, tem havido um maior foco em terapias imuno-baseadas na busca progressiva de uma cura para o HIV, incluindo vacinas terapêuticas, agonistas do recetor toll-like, anticorpos amplamente neutralizantes, inibidores do checkpoint imunológico, interferon-α e terapia com interleucinas. Também estão a decorrer estudos em que as intervenções de imunoterapia são igualmente testadas em combinação com a reversão de latência. Nesta dissertação, são apresentados e discutidos os resultados globais destas intervenções clínicas, que em última análise se direcionam para uma cura ou vacina para o HIV.
The success of antiretroviral therapy (ART) in the management of HIV infection has been one of the best in medicine in the last century. ART led to the transformation of HIV from a universal death sentence to a chronic manageable disease. In every part of the world, we have seen a dramatic reduction in HIV-related morbidity and mortality, and treatment is now available to 21 million people – over half the number of people living with this virus. However, despite these great advances over one million people die of HIV-related illnesses each year and there are 1.8 million new infections. Two profound scientific challenges remain that must be solved to truly see an end to HIV – finding a cure and an effective vaccine. Research over the past decade has resulted in a much-improved understanding of how and where HIV persists in patients on otherwise ART. It has become clear that the establishment of a latent infection in long-lived cells is the key barrier to curing HIV or allowing for sustained ART-free remission. Informed by in vitro and ex vivo studies, several therapeutic approaches aimed at depleting the pool of latently infected cells have been tested in small-scale experimental clinical trials including studies of ART intensification, genome editing, ART during acute/early infection and latency reversal. More recently, there has been an enhanced focus on immune-based therapies in the onwards search for an HIV cure including therapeutic vaccines, toll-like receptor agonists, broadly neutralizing antibodies, immune checkpoint inhibitors, interferon-α and interleukin therapy. In ongoing studies immunotherapy interventions are also tested in combination with latency reversal. In this dissertation, the overall results of these clinical interventions ultimately aimed at a cure or vaccine for HIV are presented and discussed.

Decisions to reform pharmaceutical policy often involve trade-offs between competing social and commercial goals. Canada's Access to Medicines Regime (CAMR), a reform that permits compulsory licensing for the production and export of medicines to developing countries, aimed to reconcile these goals. Since it was passed in 2004, only one order of antiretroviral drugs, enough for 21,000 HIV/AIDS patients in Rwanda for one year, has been exported. Future use of the regime appears unlikely. This research aimed to examine the politics underlying the formation of CAMR. Parliamentary committee hearing transcripts from CAMR's legislative development (2004) and from CAMR's legislative review (2007) were analyzed using a content analysis technique to identify how stakeholders who participated in the debates framed the issues. These findings were subsequently analyzed using a framework of framing, institutions and interests to determine how these three dimensions shaped CAMR's final policy design. In 2004, policy debates were dominated by two themes: intellectual property rights and TRIPS compliance. Promoting human rights and the impact of CAMR on innovation were hardly discussed. With the Departments of Industry Canada and International Trade as the lead institutions, the goals of protecting intellectual property and ensuring good trade relations with the United States appear to have taken priority over encouraging generic competition to achieve drug affordability. The result was a more limited interpretation of patent flexibilities under the WTO Paragraph 6 Decision. The most striking finding is the minimal discussion over the potential barriers developing country beneficiaries might face when attempting to use compulsory licensing, including their reluctance to use TRIPS flexibilities, their desire to pursue technological development and the constraints inherent in the WTO Paragraph 6 Decision. Instead, these issues were raised in 2007, which can be partly accounted for by a greater representation of the interests of potential beneficiary country governments. While the Government attempted to strike a balance between drug affordability and intellectual property protection, it designed CAMR as a last resort measure. Increased input from the developing country beneficiaries and shifting to institutions where the right to health gets prioritized may lead to policies that better achieves affordable drug access.