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从近期传播的病毒推断德国的HIV-1传播动态。

Inferring HIV-1 Transmission Dynamics in Germany From Recently Transmitted Viruses.

作者信息

Pouran Yousef Kaveh, Meixenberger Karolin, Smith Maureen R, Somogyi Sybille, Gromöller Silvana, Schmidt Daniel, Gunsenheimer-Bartmeyer Barbara, Hamouda Osamah, Kücherer Claudia, von Kleist Max

机构信息

*Department of Mathematics and Computer Science, Systems Pharmacology and Disease Control, Freie Universität, Berlin, Germany; †Department of Infectious Diseases, FG18 HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany; ‡Department of Hazardous Substances and Biological Agents, Biological Agents, Federal Institute for Occupational Safety and Health, Berlin, Germany; §Department of Infectious Disease Epidemiology, FG34 HIV/AIDS, STI and Blood-Borne Infections, Robert Koch Institute, Berlin, Germany; and ‖Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.

出版信息

J Acquir Immune Defic Syndr. 2016 Nov 1;73(3):356-363. doi: 10.1097/QAI.0000000000001122.

Abstract

BACKGROUND

Although HIV continues to spread globally, novel intervention strategies such as treatment as prevention (TasP) may bring the epidemic to a halt. However, their effective implementation requires a profound understanding of the underlying transmission dynamics.

METHODS

We analyzed parameters of the German HIV epidemic based on phylogenetic clustering of viral sequences from recently infected seroconverters with known infection dates. Viral baseline and follow-up pol sequences (n = 1943) from 1159 drug-naïve individuals were selected from a nationwide long-term observational study initiated in 1997. Putative transmission clusters were computed based on a maximum likelihood phylogeny. Using individual follow-up sequences, we optimized our clustering threshold to maximize the likelihood of co-clustering individuals connected by direct transmission.

RESULTS

The sizes of putative transmission clusters scaled inversely with their abundance and their distribution exhibited a heavy tail. Clusters based on the optimal clustering threshold were significantly more likely to contain members of the same or bordering German federal states. Interinfection times between co-clustered individuals were significantly shorter (26 weeks; interquartile range: 13-83) than in a null model.

CONCLUSIONS

Viral intraindividual evolution may be used to select criteria that maximize co-clustering of transmission pairs in the absence of strong adaptive selection pressure. Interinfection times of co-clustered individuals may then be an indicator of the typical time to onward transmission. Our analysis suggests that onward transmission may have occurred early after infection, when individuals are typically unaware of their serological status. The latter argues that TasP should be combined with HIV testing campaigns to reduce the possibility of transmission before TasP initiation.

摘要

背景

尽管艾滋病毒仍在全球范围内传播,但诸如治疗即预防(TasP)等新型干预策略可能会使这一流行病得到控制。然而,要有效实施这些策略,需要对潜在的传播动态有深刻的理解。

方法

我们基于来自已知感染日期的近期血清转化感染者的病毒序列的系统发育聚类,分析了德国艾滋病毒流行情况的参数。从1997年启动的一项全国性长期观察研究中,选取了1159名未接受过治疗的个体的病毒基线和随访pol序列(n = 1943)。基于最大似然系统发育计算推定的传播簇。利用个体随访序列,我们优化了聚类阈值,以最大化直接传播相连个体共同聚类的可能性。

结果

推定传播簇的大小与其丰度成反比,其分布呈现出重尾现象。基于最佳聚类阈值的簇更有可能包含来自德国同一或相邻联邦州的成员。共同聚类个体之间感染间隔时间明显短于空模型(26周;四分位间距:13 - 83)。

结论

在没有强大的适应性选择压力的情况下,病毒个体内进化可用于选择标准,以最大化传播对的共同聚类。共同聚类个体的感染间隔时间可能是后续传播典型时间的一个指标。我们的分析表明,后续传播可能在感染后早期发生,此时个体通常未意识到自己的血清学状态。这表明TasP应与艾滋病毒检测活动相结合,以降低在启动TasP之前传播的可能性。

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