Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis
Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis
复制标题
DOI：
10.1073/pnas.0708559104
复制
发表时间：
2007-10-30
影响因子：
11.1
通讯作者：
Hanage, William P.
中科院分区：
文献类型：
--
作者：
Fraser, Christophe;Hollingsworth, T. Deirdre;Hanage, William P.
HIV-1感染的自然过程的特点是病毒载量的高度异质性，不仅随着时间的推移在患者体内，而且在患者之间，特别是在感染的无症状阶段。无症状或设定点病毒载量已被证明与艾滋病发病时间缩短和传染性增加相关。本研究的目的是表征设定点病毒载量异质性的流行病学影响。通过分析两组未经治疗的患者，我们量化了病毒载量和传染性以及无症状感染期持续时间之间的关系。我们发现，由于感染的持续时间和传染性都决定了病毒传播的机会，这表明这些因素对总体传播潜力的贡献之间存在权衡。一些公共卫生影响的变化在设定点病毒载量进行了讨论。我们观察到，设定点病毒载量聚集在那些最大传播潜力的病毒周围，这使我们假设HIV-1可能已经进化到优化其传播性，这是对人类宿主群体的一种适应形式。我们讨论了如何检验这一进化假说，回顾了迄今为止可用的证据，并强调了未来研究的方向。
The natural course of HIV-1 infection is characterized by a high degree of heterogeneity in viral load, not just within patients over time, but also between patients, especially during the asymptomatic stage of infection. Asymptomatic, or set-point, viral load has been shown to correlate with both decreased time to AIDS and increased infectiousness. The aim of this study is to characterize the epidemiological impact of heterogeneity in set-point viral load. By analyzing two cohorts of untreated patients, we quantify the relationships between both viral load and infectiousness and the duration of the asymptomatic infectious period. We find that, because both the duration of infection and infectiousness determine the opportunities for the virus to be transmitted, this suggests a trade-off between these contributions to the overall transmission potential. Some public health implications of variation in set-point viral load are discussed. We observe that set-point viral loads are clustered around those that maximize the transmission potential, and this leads us to hypothesize that HIV-1 could have evolved to optimize its transmissibility, a form of adaptation to the human host population. We discuss how this evolutionary hypothesis can be tested, review the evidence available to date, and highlight directions for future research.