1 Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
2 National Centre of Epidemiology, Instituto de Salud Carlos III, Madrid, Spain.
Stat Methods Med Res. 2019 Jul;28(7):1979-1997. doi: 10.1177/0962280217746437. Epub 2017 Dec 12.
In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers' measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes' rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4-viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.
在大多数 HIV 阳性个体中,感染时间仅知介于个体开始面临 HIV 风险和诊断时间之间。然而,在某些情况下,更准确地估计感染时间非常重要。例如,推进欧洲移民获得健康服务(aMASE)研究的目标之一是确定在欧洲诊断出的 HIV 阳性移民是否在移民前或移民后感染。我们提出了一种使用 HIV 生物标志物测量、人口统计学、临床和行为数据信息来推断未知感染时间的个体特异性估计的方法。我们假设 CD4 细胞计数(CD4)和 HIV-RNA 病毒载量趋势在 HIV 感染后遵循双变量线性混合模型。利用诊断后 CD4 和病毒载量测量值并应用贝叶斯规则,我们推导出了 HIV 感染时间的后验分布,而先验分布则由诊断时的艾滋病状态和行为数据提供信息。使用具有已知 HIV 感染时间的个体的大型研究(CASCADE)的数据来估计 CD4-病毒载量和时间到艾滋病模型的参数。模拟结果显示出相当大的预测能力(例如,84%的感染被正确分类为移民前或移民后)。将该方法应用于 aMASE 研究(n=2009)表明,47%的非洲移民和 67%至 72%的其他地区移民最有可能在移民后感染。应用基于 CD4 和病毒载量的双变量建模和个体特异性信息的贝叶斯方法,我们发现 aMASE 中的大多数 HIV 阳性移民最有可能在移民到欧洲后感染。