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Seroprevalência e subtipos do vírus da hepatite C circulantes em indivíduos co-infectados com o vírus da imunodeficiência humana
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Resumo(s)
Mundialmente, estima-se que 40 milhões de pessoas estejam infectadas com VIH, 5 milhões das quais cronicamente infectadas com VHC. A co-infecção com VIH aumenta a taxa de persistência do VHC, acelera a velocidade de progressão da doença hepática e reduz significativamente a resposta à terapia do VHC. O VHC possui extensa diversidade genética, sendo classificado em seis genótipos e cerca de 90 subtipos com padrões epidemiológicos e resposta à terapia distintos. Tendo isto presente e devido a serem limitados os dados relativos aos genótipos e subtipos do VHC circulantes em Portugal e ainda ao facto de os utilizadores de drogas injectáveis (UDIs) serem um grupo de risco importante para a co-infecção por VIH e VHC, realizámos um estudo retrospectivo para determinar a prevalência da infecção por VHC e a distribuição de subtipos deste vírus num grupo de UDIs infectados com VIH.
Amostras de plasma de 66 indivíduos (1998-2001) foram testadas para anticorpos anti-VHC (ensaio imunoenzimático) e RNA do VHC (amplificação da 5’UTR por RT-PCR). Para identificar os subtipos de VHC e detectar recombinantes, as amostras com RNA viral detectável foram sujeitas a amplificação, sequenciação e análise filogenética de sequências nucleotídicas parciais para C/E1 e NS5B.
Encontrámos que 86,4% dos indivíduos possuíam anticorpos anti-VHC, 93,0% dos quais com infecção activa. Todas as amostras, exceptuando duas, com RNA viral detectável originaram amplicões para C/E1 e NS5B. A análise filogenética permitiu incluir as estirpes de VHC nos subtipos 1a (43,8%), 1b (3,6%), 2a (1,8%), 3a (21,1%), 4a (8,8%) e 4d (15,8%), revelando um padrão epidemiológico semelhante ao dos UDIs de outros países do Sul da Europa. Apenas uma amostra apresentou discordância entre os subtipos das duas regiões (4d para C/E1 e 4a para NS5B) sugerindo um potencial recombinante intragenótipo.
No total, os subtipos 1a, 4a e 4d do VHC são responsáveis por 68,4% das infecções nos UDIs infectados com VIH analisados. Considerando que apenas 20-30% dos doentes positivos para VIH e co-infectados com os genótipos 1 e 4 respondem à terapia do VHC e que ocorre transmissão do VHC dos UDIs para a população em geral, são prioritários estudos alargados de vigilância epidemiológica e implementação de estratégias de prevenção para controlar ambos os vírus neste grupo de risco.
Among the estimated 40 million persons infected with HIV worldwide, about 5 million are chronically infected with HCV. Co-infection with HIV increases HCV persistence, accelerates HCV-related liver disease, and dramatically reduces HCV treatment response rates. Based on its genetic variability, HCV has been classified into six major genotypes and about 90 subtypeswith distinct epidemiological patterns and response to therapy. With this in mind and given that the HCV genotypes and subtypes circulating in Portugal is largely unknown and that injection drug users (IDUs) are an important risk group for co-infection with HIV and HCV, we conducted a retrospectivestudy to determine the prevalence of HCV infection and HCV subtype distribution in a group of IDUs infected with HIV.Plasma samples, collected between 1998 and 2001 from 66 IDUs, were tested for anti-HCV antibodies (immunoenzymatic test) and for viral RNA (RT-PCR amplification of the 5’UTR region). To identify HCV subtypes and detect potential recombinants, samples positive for HCV RNA were further subjected to amplification, sequencing and phylogenetic analysisof partial C/E1 and NS5B sequences.We found 86.4% of the individuals with antibodies anti-HCV, 93.0% of whom showed active infection. All but two samples with detectable HCV RNA were amplified for C/E1 and NS5B regions. Phylogenetic analysis allowed us to classify the HCV strains as subtypes 1a (43.8%), 1b (3.6%), 2a (1.8%), 3a (21.1%), 4a (8.8%), and 4d (15.8%), in agreement with the epidemiologic pattern described for IDUs from Southern European countries. Globally, C/E1 and NS5B based trees demonstrated similar topologies. However, one sample presented discordant subtypes for C/E1 (4d) and NS5B (4a), suggesting infection by a potential intragenotype recombinant of HCV. Overall, HCV subtypes 1a, 4a, and 4d account for 68.4% of the infections in the group of HIV-infected IDUs under study. Considering that only 20-30% of the HIV-positive patients infected with genotypes 1 and 4 respond to current HCV therapy and the strong evidence that IDUs spread HCV to the general population, there is urgent need of further studies on HCV and HIV epidemiologic surveillance and effective preventive strategies to control both viruses in this risk group.
Among the estimated 40 million persons infected with HIV worldwide, about 5 million are chronically infected with HCV. Co-infection with HIV increases HCV persistence, accelerates HCV-related liver disease, and dramatically reduces HCV treatment response rates. Based on its genetic variability, HCV has been classified into six major genotypes and about 90 subtypeswith distinct epidemiological patterns and response to therapy. With this in mind and given that the HCV genotypes and subtypes circulating in Portugal is largely unknown and that injection drug users (IDUs) are an important risk group for co-infection with HIV and HCV, we conducted a retrospectivestudy to determine the prevalence of HCV infection and HCV subtype distribution in a group of IDUs infected with HIV.Plasma samples, collected between 1998 and 2001 from 66 IDUs, were tested for anti-HCV antibodies (immunoenzymatic test) and for viral RNA (RT-PCR amplification of the 5’UTR region). To identify HCV subtypes and detect potential recombinants, samples positive for HCV RNA were further subjected to amplification, sequencing and phylogenetic analysisof partial C/E1 and NS5B sequences.We found 86.4% of the individuals with antibodies anti-HCV, 93.0% of whom showed active infection. All but two samples with detectable HCV RNA were amplified for C/E1 and NS5B regions. Phylogenetic analysis allowed us to classify the HCV strains as subtypes 1a (43.8%), 1b (3.6%), 2a (1.8%), 3a (21.1%), 4a (8.8%), and 4d (15.8%), in agreement with the epidemiologic pattern described for IDUs from Southern European countries. Globally, C/E1 and NS5B based trees demonstrated similar topologies. However, one sample presented discordant subtypes for C/E1 (4d) and NS5B (4a), suggesting infection by a potential intragenotype recombinant of HCV. Overall, HCV subtypes 1a, 4a, and 4d account for 68.4% of the infections in the group of HIV-infected IDUs under study. Considering that only 20-30% of the HIV-positive patients infected with genotypes 1 and 4 respond to current HCV therapy and the strong evidence that IDUs spread HCV to the general population, there is urgent need of further studies on HCV and HIV epidemiologic surveillance and effective preventive strategies to control both viruses in this risk group.
Descrição
Palavras-chave
Ciências biomédicas VIH vírus da imunodeficiência humana HIV Doenças infecciosas Hepatite C Virologia SIDA Seropositividade Co-infecção
Contexto Educativo
Citação
Editora
Instituto de Higiene e Medicina Tropical