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Diversidade genética e resistência aos anti-retrovirais inibidores enzimáticos de vírus da imunodeficiência humana tipo 1 (HIV-1) de uma população de toxicodependentes por via endovenosa da grande Lisboa
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| Dissertação de Mestrado em Microbiologia Médica | 6.05 MB | Adobe PDF |
Orientador(es)
Resumo(s)
Neste estudo procedeu-se à caracterização da diversidade genética das regiões codificantes da protease (PR), transcritase reversa (RT) e integrase (IN) do gene pol do vírus da imunodeficiência humana tipo 1 (HIV-1), bem como à pesquisa de polimorfismos genéticos associados à diminuição da susceptibilidade aos anti-retrovirais inibidores enzimáticos, circulante numa população de 51 indivíduos utilizadores de drogas por via endovenosa (IDUs) da Grande Lisboa.
Em termos globais, a análise filogenética realizada com base em 38 sequências nucleotídicas concatenadas revelou que 12 (31,6%), 13 (34,2%) e 13 (34,2%) das sequências analisadas eram dos subtipos B, G/CRF14_BG e de formas genéticas não-B/não-G (1 F1, 4 CRF02_AG e 8 formas recombinantes únicas), respectivamente. Relativamente à pesquisa de mutações associadas a resistência (perfil genotípico), foram encontradas 15, presentes em 50,0% (22/44) dos indivíduos, com uma distribuição de 1-3/indivíduo (4, todas acessórias, na PR; 6 na RT; 5 na IN, uma principal e 4 acessórias). Todavia, apenas 26,7% (4/15) dessas mutações conferiam uma expressão fenotípica de resistência a uma das classes de inibidores (da RT ou IN), em 9,1% (4/44) dos indivíduos. Foi ainda observada uma elevada frequência de outros polimorfismos genéticos, mais frequentes em subtipos não-B, alguns dos quais considerados assinaturas de subtipo.
A homologia genética total ou parcial com os subtipos B e G, reconhecida neste estudo, reflectirá a sua predominância na população de IDUs. Este resultado sugere também que a epidemia de HIV-1 em Portugal poderá estar a evoluir para um padrão epidemiológico singular, no qual os subtipos B, G e suas formas recombinantes predominam.
A proporção observada de indivíduos portadores de vírus com mutações associadas a resistência, mesmo em indivíduos naive relativamente à terapêutica, indica que a sua transmissão se encontra em curso entre a população de IDUs, tendo, certamente, um impacto relevante ao nível da abordagem terapêutica e monitorização da infecção.
n this study, we intended to evaluate the genetic diversity of protease (PR), reverse transcriptase (RT) and integrase (IN) coding regions of human immunodeficiency virus type 1 (HIV-1) pol gene, as well as, to describe the genetic polymorphisms associated with decreased susceptibility to enzyme inhibitor antiretrovirals, in strains circulating in a population of 51 intravenous drug users (IDUs) from the Greater Lisbon. Overall, the phylogenetic analysis, based on 38 con catenated sequences, revealed that 12 (31.6%), 13 (34.2%) and 13 (34.2%) of the sequences analyzed were classified as subtypes B, G/CRF14_BG and other non-B/non-G genetic forms (1 F1, 4 CRF02_AG and 8 unique recombinant forms), respectively. The search for resistance- associated genetic polymorphisms (genotypic profile) revealed 15 mutations, present in 50.0% (22/44) of the subjects, with a distribution of 1-3/individual (4 minor in PR; 6 in RT; 5 in IN, one major and 4 minor). However, only 26.7% (4/15) of these mutations confer a phenotypic profile of resistance and just to one class of inhibitors (RT or IN), being found in 9.1% (4/44) of the subjects. It was also observed a high frequency of other genetic polymorphisms, most often in non-B subtypes, some of which are considered subtype signatures. The total or partial genetic homology of our sequences with subtypes B and G, identified in this study, reflects their prevalence in this population of IDUs. This finding suggests that the HIV-1 epidemics in Portugal may be evolving into a unique epidemiological pattern, in which subtypes B, G and their recombinant forms predominate. The observed ratio of subjects infected with viruses carrying mutations associated with resistance, even in therapy-naive individuals, indicates that the transmission is ongoing among IDUs. This fact will surely have an impact on antiretroviral therapy implementation and monitoring of infection in this population.
n this study, we intended to evaluate the genetic diversity of protease (PR), reverse transcriptase (RT) and integrase (IN) coding regions of human immunodeficiency virus type 1 (HIV-1) pol gene, as well as, to describe the genetic polymorphisms associated with decreased susceptibility to enzyme inhibitor antiretrovirals, in strains circulating in a population of 51 intravenous drug users (IDUs) from the Greater Lisbon. Overall, the phylogenetic analysis, based on 38 con catenated sequences, revealed that 12 (31.6%), 13 (34.2%) and 13 (34.2%) of the sequences analyzed were classified as subtypes B, G/CRF14_BG and other non-B/non-G genetic forms (1 F1, 4 CRF02_AG and 8 unique recombinant forms), respectively. The search for resistance- associated genetic polymorphisms (genotypic profile) revealed 15 mutations, present in 50.0% (22/44) of the subjects, with a distribution of 1-3/individual (4 minor in PR; 6 in RT; 5 in IN, one major and 4 minor). However, only 26.7% (4/15) of these mutations confer a phenotypic profile of resistance and just to one class of inhibitors (RT or IN), being found in 9.1% (4/44) of the subjects. It was also observed a high frequency of other genetic polymorphisms, most often in non-B subtypes, some of which are considered subtype signatures. The total or partial genetic homology of our sequences with subtypes B and G, identified in this study, reflects their prevalence in this population of IDUs. This finding suggests that the HIV-1 epidemics in Portugal may be evolving into a unique epidemiological pattern, in which subtypes B, G and their recombinant forms predominate. The observed ratio of subjects infected with viruses carrying mutations associated with resistance, even in therapy-naive individuals, indicates that the transmission is ongoing among IDUs. This fact will surely have an impact on antiretroviral therapy implementation and monitoring of infection in this population.
Descrição
Palavras-chave
Microbiologia médica Biologia molecular Doenças infecciosas HIV-1 Sida Terapêutica Antiretrovirais
Contexto Educativo
Citação
Editora
Instituto de Higiene e Medicina Tropical