Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
Proc Natl Acad Sci U S A. 2022 Sep 20;119(38):e2210604119. doi: 10.1073/pnas.2210604119. Epub 2022 Sep 14.
Inferring the transmission direction between linked individuals living with HIV provides unparalleled power to understand the epidemiology that determines transmission. Phylogenetic ancestral-state reconstruction approaches infer the transmission direction by identifying the individual in whom the most recent common ancestor of the virus populations originated. While these methods vary in accuracy, it is unclear why. To evaluate the performance of phylogenetic ancestral-state reconstruction to determine the transmission direction of HIV-1 infection, we inferred the transmission direction for 112 transmission pairs where transmission direction and detailed additional information were available. We then fit a statistical model to evaluate the extent to which epidemiological, sampling, genetic, and phylogenetic factors influenced the outcome of the inference. Finally, we repeated the analysis under real-life conditions with only routinely available data. We found that whether ancestral-state reconstruction correctly infers the transmission direction depends principally on the phylogeny's topology. For example, under real-life conditions, the probability of identifying the correct transmission direction increases from 32%-when a monophyletic-monophyletic or paraphyletic-polyphyletic tree topology is observed and when the tip closest to the root does not agree with the state at the root-to 93% when a paraphyletic-monophyletic topology is observed and when the tip closest to the root agrees with the root state. Our results suggest that documenting larger differences in relative intrahost diversity increases our confidence in the transmission direction inference of linked pairs for population-level studies of HIV. These findings provide a practical starting point to determine our confidence in transmission direction inference from ancestral-state reconstruction.
推断与 HIV 共存的个体之间的传播方向，为了解决定传播的流行病学提供了无与伦比的力量。系统发育祖先状态重建方法通过识别病毒群体最近共同祖先起源的个体来推断传播方向。虽然这些方法在准确性上有所不同，但原因尚不清楚。为了评估系统发育祖先状态重建确定 HIV-1 感染传播方向的性能，我们推断了 112 对传播对中传播方向和详细附加信息可用的传播方向。然后，我们拟合了一个统计模型，以评估流行病学、采样、遗传和系统发育因素在多大程度上影响推断结果。最后，我们仅使用常规可用数据在实际条件下重复了分析。我们发现，祖先状态重建是否正确推断传播方向主要取决于系统发育的拓扑结构。例如，在实际条件下，当观察到单系-单系或并系-多系树拓扑结构，并且最接近根的尖端与根状态不一致时，正确识别传播方向的概率从 32%增加到 93%当观察到并系-单系拓扑结构，并且最接近根的尖端与根状态一致时。我们的结果表明，记录宿主内相对多样性的更大差异增加了我们对 HIV 人群水平研究中连锁对传播方向推断的信心。这些发现为从祖先状态重建确定我们对传播方向推断的信心提供了一个实用的起点。
