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Abstract(s)
A presente dissertação encontra-se integrada na unidade curricular Estágio, do Mestrado Integrado em Ciências Farmacêuticas, a qual englobou uma componente de investigação e uma componente profissional. A primeira compreendeu uma revisão bibliográfica no âmbito do VIH/SIDA (Capítulo I) e a segunda alusiva ao estágio realizado em farmácia comunitária (Capítulo II).
O primeiro capítulo deste documento corresponde ao artigo de revisão da literatura referente à mutação viral K65R e à sua influência na Profilaxia de Pré-exposição (PrEP) da infeção por VIH-1 no adulto. A PrEP constitui uma nova abordagem que previne a infeção pelo VIH-1 através da administração de um comprimido. O comprimido em questão é o Truvada®, que corresponde à associação de duas substâncias, Tenofovir disoproxil fumarato e Emtricitabina. A PrEP é destinada aos indivíduos seronegativos, mas com elevado risco de aquisição da infeção por VIH-1. As resistências do VIH-1 aos antirretrovirais que constituem a PrEP podem constituir uma ameaça ao sucesso desta ferramenta preventiva. Há mutações no VIH-1, como a K65R, que demonstraram diminuir a suscetibilidade do vírus ao Truvada®. O presente trabalho procurou investigar o impacto do VIH-1, portador da mutação K65R, na eficácia do Truvada® como ferramenta preventiva. Tendo em conta que este medicamento já era usado no tratamento da infeção por VIH-1, existem estirpes deste vírus que integram mutações de resistência específicas, com potencial para serem transmitidas aos indivíduos seronegativos e a fazer PrEP. Reveste-se de elevada pertinência entender também a influência da PrEP na promoção de resistências, associadas à mutação K65R, uma vez que há indivíduos que podem iniciar a PrEP com infeção aguda pelo VIH-1 indetetável e o desenvolvimento desta resistência pode comprometer os esquemas terapêuticos aplicados em tratamentos futuros. Deste modo, numa instância inicial, foram analisados os diferentes subtipos de VIH-1 e alguns polimorfismos característicos que revelaram ser decisivos para o desenvolvimento de resistências aos antirretrovirais, à posteriori caracterizou-se o possível mecanismo de génese da mutação K65R, mecanismo de resistência farmacológica associado à mutação viral K65R e possíveis repercussões da transmissão desta mutação, no contexto da PrEP. Ainda foi realizada uma breve contextualização da PrEP em Portugal e da mutação K65R em doentes portugueses infetados com VIH-1. Por fim, foram avaliados estudos in vitro e em animais referentes à eficácia do Truvada® mediante o VIH-1 portador da mutação K65R. Os principais ensaios clínicos realizados com a PrEP também foram foco de análise, mais concretamente a deteção, nestes ensaios, de mutações de resistência aos antirretrovirais em estudo.
O segundo capítulo aborda a componente de estágio em farmácia comunitária, o qual foi realizado na Farmácia Sant´Ana, na Covilhã, entre os dias 22 de janeiro e 1 de junho. O período de estágio alargado permitiu contactar, de forma detalhada, com a prática farmacêutica no contexto de farmácia comunitária, no âmbito da organização da farmácia, gestão e contabilidade, legislação farmacêutica, medicamentos e outros produtos de saúde, aprovisionamento e armazenamento, atendimento ao balcão, aconselhamento farmacêutico, serviços farmacêuticos, outros serviços de promoção da saúde e bem-estar e preparação de manipulados.
This dissertation is part of a curricular unit named Internship, part of the Integrated Master of Pharmaceutical Sciences which included a research component and a professional component. The first one included a bibliographical review referent to HIV/AIDS (Chapter I) and the second about community pharmacy (Chapter II). The first chapter of this document corresponds to the literature review article about the K65R viral mutation and its influence on Pre-exposure Prophylaxis (PrEP) of HIV-1 infection in adults. PrEP is a new approach that prevents HIV-1 infection through the administration of a tablet. The name of the tablet is Truvada®, which corresponds to the combination of two substances, Tenofovir disoproxil fumarate and Emtricitabine. PrEP is intended for seronegative individuals, but at high risk for HIV-1 infection. The resistance of HIV-1 to the antiretrovirals that constitute PrEP represent a threat to the success of this preventive tool. There are mutations in HIV-1, such as K65R, which has been shown to decrease the susceptibility of the virus to Truvada®. The objective of this study was investigate the impact of HIV-1 harboring K65R mutation in this preventive tool, considering that this drug was already used in the treatment of HIV-1 infection and, therefore, there are pharmacological resistances with potential to be transmitted to individuals on PrEP. It is highly relevant to understand the risk of developing resistances associated with the K65R mutation from PrEP since there are individuals who can initiate PrEP with undiagnosed HIV-1 acute infection and the development of this resistance may compromise therapeutic regimens used in future treatments. Thus, an analysis about different HIV-1 subtypes and some characteristic polymorphisms, the possible mechanism of the K65R genesis, pharmacological resistance mechanism and repercussions of K65R transmission in the context of PrEP was performed. A brief contextualization of PrEP in Portugal and the K65R mutation in Portuguese patients infected with HIV-1 were also performed. Finally, in vitro and animal studies about the efficacy of Truvada® against HIV-1 harboring the K65R mutation were evaluated. The major clinical trials conducted with PrEP were also focus of analysis, more specifically the detection of antiretroviral resistance mutations. The second chapter refers to the internship component in community pharmacy, which was held at the Sant'Ana Pharmacy in Covilhã between 22nd January and 1st June. The extended period of the internship allowed a detailed contact with the pharmaceutical practice in the context of community pharmacy, in the scope of pharmacy organization, management and accounting, pharmaceutical legislation, medicines and other health products, provisioning and storage, attendance, pharmaceutical advice, pharmaceutical services, other health promotion and wellness services and preparation of manipulated drugs.
This dissertation is part of a curricular unit named Internship, part of the Integrated Master of Pharmaceutical Sciences which included a research component and a professional component. The first one included a bibliographical review referent to HIV/AIDS (Chapter I) and the second about community pharmacy (Chapter II). The first chapter of this document corresponds to the literature review article about the K65R viral mutation and its influence on Pre-exposure Prophylaxis (PrEP) of HIV-1 infection in adults. PrEP is a new approach that prevents HIV-1 infection through the administration of a tablet. The name of the tablet is Truvada®, which corresponds to the combination of two substances, Tenofovir disoproxil fumarate and Emtricitabine. PrEP is intended for seronegative individuals, but at high risk for HIV-1 infection. The resistance of HIV-1 to the antiretrovirals that constitute PrEP represent a threat to the success of this preventive tool. There are mutations in HIV-1, such as K65R, which has been shown to decrease the susceptibility of the virus to Truvada®. The objective of this study was investigate the impact of HIV-1 harboring K65R mutation in this preventive tool, considering that this drug was already used in the treatment of HIV-1 infection and, therefore, there are pharmacological resistances with potential to be transmitted to individuals on PrEP. It is highly relevant to understand the risk of developing resistances associated with the K65R mutation from PrEP since there are individuals who can initiate PrEP with undiagnosed HIV-1 acute infection and the development of this resistance may compromise therapeutic regimens used in future treatments. Thus, an analysis about different HIV-1 subtypes and some characteristic polymorphisms, the possible mechanism of the K65R genesis, pharmacological resistance mechanism and repercussions of K65R transmission in the context of PrEP was performed. A brief contextualization of PrEP in Portugal and the K65R mutation in Portuguese patients infected with HIV-1 were also performed. Finally, in vitro and animal studies about the efficacy of Truvada® against HIV-1 harboring the K65R mutation were evaluated. The major clinical trials conducted with PrEP were also focus of analysis, more specifically the detection of antiretroviral resistance mutations. The second chapter refers to the internship component in community pharmacy, which was held at the Sant'Ana Pharmacy in Covilhã between 22nd January and 1st June. The extended period of the internship allowed a detailed contact with the pharmaceutical practice in the context of community pharmacy, in the scope of pharmacy organization, management and accounting, pharmaceutical legislation, medicines and other health products, provisioning and storage, attendance, pharmaceutical advice, pharmaceutical services, other health promotion and wellness services and preparation of manipulated drugs.
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Keywords
Farmácia Comunitária. Mutação K65r Prep Profilaxia de Pré-Exposição Resistências à Prep Resistências Ao Tenofovir Truvada®