Bartlett Sofia R, Wertheim Joel O, Bull Rowena A, Matthews Gail V, Lamoury Francois Mj, Scheffler Konrad, Hellard Margaret, Maher Lisa, Dore Gregory J, Lloyd Andrew R, Applegate Tanya L, Grebely Jason
Kirby Institute, UNSW Australia, Sydney, 2052, Australia.
Department of Medicine, University of California, San Diego, California, 92093, United States.
J Viral Hepat. 2017 May;24(5):404-411. doi: 10.1111/jvh.12652. Epub 2016 Nov 24.
Combining phylogenetic and network methodologies has the potential to better inform targeted interventions to prevent and treat infectious diseases. This study reconstructed a molecular transmission network for people with recent hepatitis C virus (HCV) infection and modelled the impact of targeting directly acting antiviral (DAA) treatment for HCV in the network. Participants were selected from three Australian studies of recent HCV from 2004 to 2014. HCV sequence data (Core-E2) from participants at the time of recent HCV detection were analysed to infer a network by connecting pairs of sequences whose divergence was ≤.03 substitutions/site. Logistic regression was used to identify factors associated with connectivity. Impact of targeting HCV DAAs at both HIV co-infected and random nodes was simulated (1 million replicates). Among 236 participants, 21% (n=49) were connected in the network. HCV/HIV co-infected participants (47%) were more likely to be connected compared to HCV mono-infected participants (16%) (OR 4.56; 95% CI; 2.13-9.74). Simulations targeting DAA HCV treatment to HCV/HIV co-infected individuals prevented 2.5 times more onward infections than providing DAAs to randomly selected individuals. Results demonstrate that genetic distance-based network analyses can be used to identify characteristics associated with HCV transmission, informing targeted prevention and treatment strategies.
结合系统发育和网络方法有潜力为预防和治疗传染病的针对性干预措施提供更充分的信息。本研究重建了近期丙型肝炎病毒(HCV)感染者的分子传播网络,并模拟了在该网络中针对HCV直接作用抗病毒药物(DAA)治疗的影响。参与者选自2004年至2014年澳大利亚三项关于近期HCV感染的研究。分析了参与者在近期检测到HCV时的HCV序列数据(核心-E2),通过连接差异≤0.03个替换/位点的序列对来推断网络。使用逻辑回归来确定与连通性相关的因素。模拟了在HIV合并感染节点和随机节点上靶向HCV DAA的影响(100万次重复)。在236名参与者中,21%(n = 49)在网络中相互连接。与HCV单一感染参与者(16%)相比,HCV/HIV合并感染参与者(47%)更有可能相互连接(比值比4.56;95%置信区间;2.13 - 9.74)。将DAA HCV治疗靶向HCV/HIV合并感染个体的模拟比向随机选择的个体提供DAA预防的后续感染多2.5倍。结果表明,基于遗传距离的网络分析可用于识别与HCV传播相关的特征,为针对性的预防和治疗策略提供信息。