Vitalant Research Institute, San Francisco, CA, USA.
University of California, San Francisco, San Francisco, CA, USA.
Epidemiol Infect. 2020 Feb 19;148:e53. doi: 10.1017/S0950268820000503.
Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the 'Fiebig staging system' has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying 'sensitivity'. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define 'stages' of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.
准确的方法来确定个体 HIV 感染的持续时间在许多情况下都很有价值，包括许多关键的研究和临床实践（特别是对于急性感染）。自 2003 年首次发表以来，“Fiebig 分期系统”一直被用作根据新诊断个体中 HIV 检测结果模式将早期 HIV 感染分类为五个连续阶段的主要方法。然而，只有在同一天对同一人进行阴性和阳性检测，并在特定的、具有不同“敏感性”的检测对中进行检测时，才能对 Fiebig 阶段进行分期。此外，在过去的 16 年中，HIV 检测技术有了很大的发展，用于定义 Fiebig 分期的五个关键检测中的三个已经不再广泛使用。为了解决这些局限性，我们开发了一种改进的、更通用的框架，通过将任何组合的诊断检测结果（无论是在同一天还是多天获得的）解释为可检测感染的估计日期，即 EDDI，来估计 HIV 感染的持续时间。EDDI 方法相对于 Fiebig 分期的一个关键优势是，它允许为任何至少有一次阳性和一次阴性 HIV 检测的人生成一个单点估计值，以及首次可检测到感染的日期的相关可信度区间。这些检测不必在同一天进行；它们不必在感染的急性期进行，该方法也不依赖于任何特殊的配对检测来定义感染的“阶段”。EDDI 周围区间的大小（因此估计本身的精度）在很大程度上取决于阴性和阳性检测之间的时间长度。EDDI 方法也很灵活，可以无缝地纳入任何具有合理诊断延迟估计的检测。一个开源的、免费的在线工具包括一个用户可更新的、经过精心策划的已发表诊断延迟数据库。自 15 多年前首次发表以来，HIV 诊断技术已经有了巨大的发展，现在是时候对用于估计感染时间的方法进行类似的发展了。EDDI 方法是在不断发展的诊断环境中估计 HIV 感染时间的一种灵活而严格的方法。
