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Therapeutic advancements in the management of HIV/AIDS
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Resumo(s)
A infeção pelo vírus da imunodeficiência humana tornou-se numa epidemia global que está a
entrar na sua quarta década. Estima-se que, desde a descoberta deste vírus, 79,3 milhões (55,9-
110 milhões) de pessoas foram infetadas e que dessas, 36,3 milhões (27,2 milhões-47,8
milhões) perderam as suas vidas. Podemos dividir este retrovírus em dois tipos: tipo 1 e tipo 2.
Ambas as espécies pertencem ao grupo dos Lentivirus, que por sua vez pertencem à família e
subfamília Retroviridae e Orthoretrovirinae, respetivamente. Ambos possuem a mesma
estrutura genética básica, o mesmo mecanismo de replicação intracelular, via de transmissão e
progressão da doença; no entanto, eles pertencem a linhagens diferentes, ou seja, representam
transmissões entre espécies distintas (zoonose). A síndrome da imunodeficiência humana
adquirida é o estadio final da progressão viral e, se não for tratada, acaba com a morte do doente.
Com um melhor entendimento da replicação viral e dos mecanismos utilizados para evadir a
imunidade do nosso organismo, os alvos para interromper a produção viral também se tornaram
mais claros. Atualmente, existe um arsenal de mais de 30 fármacos antirretrovirais, que
possuem oito mecanismos de ação distintos. O vírus que antes era visto como uma sentença de
morte para todos que o contraíam, é agora é uma doença crónica que pode ser controlada com
terapia existente. Esta dissertação está dividida em 4 partes: origem e descoberta do HIV;
mecanismo de replicação viral; Terapia antirretroviral; avanços na manutenção da terapêutica
do HIV. O objetivo principal do trabalho é entender como uma zoonose com origem em África
conseguiu espalhar-se pelo mundo e até hoje permanece sem cura. Será também abordada a
progressão da terapêutica disponível e dos medicamentos aprovados ao longo dos anos, desde
os primeiros medicamentos que causavam efeitos secundários graves e que eram facilmente
suscetíveis à resistência viral devido à ocorrência de mutações no início dos anos 90 até 2021,
onde é utilizada uma terapêutica dupla ou tripla, sem que exista toxicidade para o doente e com
uma excelente relação benefício-risco. Também serão abordados fármacos e vacinas em ensaios
clínicos para o tratamento deste retrovírus, que poderão vir a ser aprovados num futuro a médio/longo prazo.
The human immunodeficiency virus has become a global epidemic that is now entering his fourth decade. It is estimated that since the discovery of this virus, 79.3 million (55.9 million 110 million) people have become infected and 36.3 million (27.2 million-47.8 million) have lost their lives. We can divide this retrovirus into two main types: 1 and 2. Both species belong to the Lentivirus group, that belongs to the Retroviridae Orthoretrovirinae family and subfamily, respectively. Both types share the same basic gene arrangement, equal intracellular replication mechanism, transmission pathway and disease progression however they belong to different lineages and furthermore represent distinctive cross-species transmissions (zoonosis). The acquired human immunodeficiency syndrome is the final stage of viral progression and it ends up in death if not treated. With the better understanding of viral replication and their mechanisms to evade immunity, the targets to stop viral production also became clearer. Nowadays, we are in possession of an armory of more than 30 antiretroviral agents, acting through eight different mechanisms. The virus that once was a death sentence for everyone who caught it, is now a chronic disease that can be managed by the existing therapy. This dissertation is divided in 4 parts: origin and discovery of HIV; mechanism of viral replication; antiretroviral therapy; advancements in the management of HIV. The main purpose of the work is to understand how a zoonosis originated in Africa was able to spread throughout the world and until this day remains with no cure. It will also approach the progression of the approved drugs throughout the years, from the 1-2 medicines that caused brutal side effects and were easily prone to resistance mutations in the beginning of the 90s to 2021, where 2-3 medicines are simultaneously used in almost non-toxic, with little to no side effects in the treatment of this retrovirus, along with possible drugs that could be approved in a medium-long term.
The human immunodeficiency virus has become a global epidemic that is now entering his fourth decade. It is estimated that since the discovery of this virus, 79.3 million (55.9 million 110 million) people have become infected and 36.3 million (27.2 million-47.8 million) have lost their lives. We can divide this retrovirus into two main types: 1 and 2. Both species belong to the Lentivirus group, that belongs to the Retroviridae Orthoretrovirinae family and subfamily, respectively. Both types share the same basic gene arrangement, equal intracellular replication mechanism, transmission pathway and disease progression however they belong to different lineages and furthermore represent distinctive cross-species transmissions (zoonosis). The acquired human immunodeficiency syndrome is the final stage of viral progression and it ends up in death if not treated. With the better understanding of viral replication and their mechanisms to evade immunity, the targets to stop viral production also became clearer. Nowadays, we are in possession of an armory of more than 30 antiretroviral agents, acting through eight different mechanisms. The virus that once was a death sentence for everyone who caught it, is now a chronic disease that can be managed by the existing therapy. This dissertation is divided in 4 parts: origin and discovery of HIV; mechanism of viral replication; antiretroviral therapy; advancements in the management of HIV. The main purpose of the work is to understand how a zoonosis originated in Africa was able to spread throughout the world and until this day remains with no cure. It will also approach the progression of the approved drugs throughout the years, from the 1-2 medicines that caused brutal side effects and were easily prone to resistance mutations in the beginning of the 90s to 2021, where 2-3 medicines are simultaneously used in almost non-toxic, with little to no side effects in the treatment of this retrovirus, along with possible drugs that could be approved in a medium-long term.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
HIV AIDS Antiretroviral Therapy Replication Mestrado integrado - 2021