Loading...
Publication
FarmacogenĂ©tica aplicada aos inibidores da integrase na terapĂȘutica antirretroviral
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 1.25 MB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
De acordo com a Organização Mundial de SaĂșde, no final de 2019 existia aproximadamente 38 milhĂ”es de infetados com o VĂrus da ImunodeficiĂȘncia Humana (HIV). Este nĂșmero elevado deve-se sobretudo ao aumento da esperança mĂ©dia de vida das pessoas infetadas a realizar terapĂȘutica antirretroviral.
Ao longo dos anos, esta terapĂȘutica sofreu ajustes e foram descobertos vĂĄrios antirretrovirais bastante eficazes como os inibidores da integrase. Contudo, existem mutaçÔes no HIV que fazem diminuir a eficĂĄcia da terapĂȘutica e existem variaçÔes genĂ©ticas entre os seres humanos que fazem com que cada organismo seja diferente, alterando a sua eficĂĄcia e toxicidade.
Nesta revisĂŁo bibliogrĂĄfica foi possĂvel pesquisar e analisar os vĂĄrios polimorfismos existentes para os inibidores da integrase bem como para as mutaçÔes do HIV.
Foi possĂvel encontrar vĂĄrias mutaçÔes primĂĄrias e secundĂĄrias para o HIV que influenciam a eficĂĄcia dos inibidores da integrase, por exemplo Y143C/H/R, N155H e Q148H/K/R para o Raltegravir.
Também foram pesquisados vårios polimorfismos genéticos entre os quais se destacam rs2231142 para Dolutegravir e UGT1A1*28 para Raltegravir.
Apesar de haver vĂĄrias variantes genĂ©ticas encontradas e analisadas para o Raltegravir e Dolutegravir, a significĂąncia clĂnica da maioria destas ainda nĂŁo geram concordĂąncia na comunidade cientĂfica. Assim, a grande conclusĂŁo desta monografia serĂĄ alertar para a falta de meta-anĂĄlises para os polimorfismos jĂĄ investigados e para a falta de estudos para os polimorfismos dos inibidores que nĂŁo tem investigaçÔes efetuadas.
According to the World Health Organization, in the end of 2019 there were approximately 38 million infected with the Human Immunodeficiency Virus (HIV). This high number is mainly due to the increase of the average life expectancy of people infected with antiretroviral therapy. Over the years, this therapy has undergone adjustments and several effective antiretrovirals have been discovered, such as integrase inhibitors. However, there are mutations in HIV that decrease the effectiveness of therapy and there are genetic variations among humans that make each organism different, changing its effectiveness and toxicity. In this bibliographic review was possible to research and analyze the various existing polymorphisms for integrase inhibitors as well as for HIV mutations. It has been possible to find several primary and secondary mutations for HIV that influence the effectiveness of integrase inhibitors, for example Y143C/H/R, N155H and Q148H/K/R for Raltegravir. Several genetic polymorphisms were also researched, among which rs2231142 stands out for Dolutegravir and UGT1A1*28 for Raltegravir. Although there are several genetic variants found and analyzed for Raltegravir and Dolutegravir, the clinical significance of most of these still does not generate agreement in the scientific community. So, the big conclusion of this monograph will be to warn about the lack of meta-analyzes for the polymorphisms already investigated and for the lack of studies for the polymorphisms of inhibitors that have not been investigated.
According to the World Health Organization, in the end of 2019 there were approximately 38 million infected with the Human Immunodeficiency Virus (HIV). This high number is mainly due to the increase of the average life expectancy of people infected with antiretroviral therapy. Over the years, this therapy has undergone adjustments and several effective antiretrovirals have been discovered, such as integrase inhibitors. However, there are mutations in HIV that decrease the effectiveness of therapy and there are genetic variations among humans that make each organism different, changing its effectiveness and toxicity. In this bibliographic review was possible to research and analyze the various existing polymorphisms for integrase inhibitors as well as for HIV mutations. It has been possible to find several primary and secondary mutations for HIV that influence the effectiveness of integrase inhibitors, for example Y143C/H/R, N155H and Q148H/K/R for Raltegravir. Several genetic polymorphisms were also researched, among which rs2231142 stands out for Dolutegravir and UGT1A1*28 for Raltegravir. Although there are several genetic variants found and analyzed for Raltegravir and Dolutegravir, the clinical significance of most of these still does not generate agreement in the scientific community. So, the big conclusion of this monograph will be to warn about the lack of meta-analyzes for the polymorphisms already investigated and for the lack of studies for the polymorphisms of inhibitors that have not been investigated.
Description
Dissertação para obtenção do grau de Mestre no Instituto Universitårio Egas Moniz
Keywords
HIV InSTI Polimorfismo MutaçÔes