van de Laar Thijis, Pybus Oliver, Bruisten Sylvia, Brown David, Nelson Mark, Bhagani Sanjay, Vogel Martin, Baumgarten Alex, Chaix Marie-Laure, Fisher Martin, Gotz Hannelore, Matthews Gail V, Neifer Stefan, White Peter, Rawlinson William, Pol Stanislav, Rockstroh Jurgen, Coutinho Roel, Dore Greg J, Dusheiko Geoffrey M, Danta M
Cluster of Infectious Diseases, Health Service, Amsterdam, The Netherlands.
Gastroenterology. 2009 May;136(5):1609-17. doi: 10.1053/j.gastro.2009.02.006.
BACKGROUND & AIMS: Since 2000, there has been a marked rise in acute hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). We conducted an international phylogenetic study to investigate the existence of an HCV transmission network among MSM.
HIV-positive MSM diagnosed with recent HCV (n = 226) in England (107), The Netherlands (58), France (12), Germany (25), and Australia (24) between 2000 and 2006 were enrolled into a molecular phylogenetic study. Using real-time polymerase chain reaction (PCR), the NS5B region of the HCV genome (436 base pair) was amplified, sequenced, and compared with unrelated NS5B sequences.
NS5B sequences were obtained from 200 (89%) cases. Circulating HCV genotypes were 1a (59%), 4d (23%), 3a (11%), 1b (5%), and 2b/c (3%). Phylogenetic analysis revealed 156 (78%) sequences that formed 11 clusters (bootstrap value > 70%) containing between 4 and 37 individual sequences. Country mixing was associated with larger cluster size (17 vs 4.5 sequences; P = .03). "Molecular clock" analysis indicated that the majority (85%) of transmissions occurred since 1996.
Phylogenetic analysis revealed a large international network of HCV transmission among HIV-positive MSM. The rapid spread of HCV among neighboring countries is supported by the large proportion (74%) of European MSM infected with an HCV strain co-circulating in multiple European countries, the low evolutionary distances among HCV isolates from different countries, and the trend toward increased country mixing with increasing cluster size. Temporally, this epidemic coincides with the introduction of highly active antiretroviral therapy and associated increases in sexual risk behaviors. International collaborative public health efforts are needed to mitigate HCV transmission among this population.
自2000年以来,人类免疫缺陷病毒(HIV)阳性的男男性行为者(MSM)中急性丙型肝炎病毒(HCV)感染率显著上升。我们开展了一项国际系统发育研究,以调查MSM中HCV传播网络的存在情况。
2000年至2006年间,在英格兰(107例)、荷兰(58例)、法国(12例)、德国(25例)和澳大利亚(24例)诊断为近期感染HCV的HIV阳性MSM(n = 226)被纳入一项分子系统发育研究。使用实时聚合酶链反应(PCR)扩增、测序HCV基因组的NS5B区域(436个碱基对),并与不相关的NS5B序列进行比较。
从200例(89%)病例中获得了NS5B序列。流行的HCV基因型为1a(59%)、4d(23%)、3a(11%)、1b(5%)和2b/c(3%)。系统发育分析显示,156例(78%)序列形成了11个簇(自展值>70%),每个簇包含4至37个个体序列。国家间混合与更大的簇大小相关(17个序列对4.5个序列;P = 0.03)。“分子钟”分析表明,大多数(85%)传播发生在1996年以后。
系统发育分析揭示了HIV阳性MSM中一个庞大的国际HCV传播网络。HCV在邻国之间的快速传播得到以下因素支持:很大比例(74%)的欧洲MSM感染了在多个欧洲国家共同流行的HCV毒株、来自不同国家的HCV分离株之间进化距离较短,以及随着簇大小增加国家间混合增加的趋势。在时间上,这一流行与高效抗逆转录病毒疗法的引入以及性风险行为的相应增加相吻合。需要开展国际合作公共卫生努力,以减轻该人群中的HCV传播。