The Impact of Clinical, Demographic and Risk Factors on Rates of HIV Transmission: A Population-based Phylogenetic Analysis in British Columbia, Canada

The Impact of Clinical, Demographic and Risk Factors on Rates of HIV Transmission: A Population-based Phylogenetic Analysis in British Columbia, Canada
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DOI:
10.1093/infdis/jiu560
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发表时间:
2015-03-15
影响因子:
6.4
通讯作者:
Harrigan, P. Richard
Harrigan, P. Richard
中科院分区:
医学2区
文献类型:
--
作者:
Poon, Art F. Y.;Joy, Jeffrey B.;Harrigan, P. Richard

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背景人类免疫缺陷病毒(HIV)的多样化是由其传播历史形成的。因此,我们使用了人口为基础的全省艾滋病毒耐药性数据库在不列颠哥伦比亚省(BC),加拿大,以评估临床,人口和行为因素对艾滋病毒传播率的影响。我们从27296个匿名的批量HIV pol序列中重建了分子遗传学,这些序列代表了BC中的7747个个体,大约是BC中估计的HIV流行率的一半。根据系统发育距离将感染分组为簇,作为传播率变化的代表。根据估计的HIV血清转化日期重建聚集性扩张率。我们的标准将4431名个体分为744个群组,这些群组在很大程度上与风险因素有关,包括以注射吸毒者为主的大型既定群组和最近出现的由男男性行为者组成的群组。一个个体的系统发生邻居(由5个具有最短系统发生距离的其他个体组成)的平均log(10)病毒载量使其出现在一个簇中的几率增加>2倍/log(10)病毒/毫升。通过对艾滋病毒耐药性基因型的二次分析,可以在接近真实的时间内确定正在进行的艾滋病毒传播热点的特征,为有针对性地采取预防艾滋病毒的公共卫生举措提供重要的潜在资源。
Background. The diversification of human immunodeficiency virus (HIV) is shaped by its transmission history. We therefore used a population based province wide HIV drug resistance database in British Columbia (BC), Canada, to evaluate the impact of clinical, demographic, and behavioral factors on rates of HIV transmission.Methods. We reconstructed molecular phylogenies from 27 296 anonymized bulk HIV pol sequences representing 7747 individuals in BC-about half the estimated HIV prevalence in BC. Infections were grouped into clusters based on phylogenetic distances, as a proxy for variation in transmission rates. Rates of cluster expansion were reconstructed from estimated dates of HIV seroconversion.Results. Our criteria grouped 4431 individuals into 744 clusters largely separated with respect to risk factors, including large established clusters predominated by injection drug users and more-recently emerging clusters comprising men who have sex with men. The mean log(10) viral load of an individual's phylogenetic neighborhood (composed of 5 other individuals with shortest phylogenetic distances) increased their odds of appearing in a cluster by >2-fold per log(10) viruses per milliliter.Conclusions. Hotspots of ongoing HIV transmission can be characterized in near real time by the secondary analysis of HIV resistance genotypes, providing an important potential resource for targeting public health initiatives for HIV prevention.