Department of Mathematics, Stockholm University, Stockholm, Sweden.
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Int J Epidemiol. 2019 Dec 1;48(6):1795-1803. doi: 10.1093/ije/dyz100.
Most HIV infections originate from individuals who are undiagnosed and unaware of their infection. Estimation of this quantity from surveillance data is hard because there is incomplete knowledge about (i) the time between infection and diagnosis (TI) for the general population, and (ii) the time between immigration and diagnosis for foreign-born persons.
We developed a new statistical method for estimating the incidence of HIV-1 and the number of undiagnosed people living with HIV (PLHIV), based on dynamic modelling of heterogeneous HIV-1 surveillance data. The methods consist of a Bayesian non-linear mixed effects model using multiple biomarkers to estimate TI of HIV-1-positive individuals, and a novel incidence estimator which distinguishes between endogenous and exogenous infections by modelling explicitly the probability that a foreign-born person was infected either before or after immigration. The incidence estimator allows for direct calculation of the number of undiagnosed persons. The new methodology is illustrated combining heterogeneous surveillance data from Sweden between 2003 and 2015.
A leave-one-out cross-validation study showed that the multiple-biomarker model was more accurate than single biomarkers (mean absolute error 1.01 vs ≥1.95). We estimate that 816 [95% credible interval (CI) 775-865] PLHIV were undiagnosed in 2015, representing a proportion of 10.8% (95% CI 10.3-11.4%) of all PLHIV.
The proposed methodology will enhance the utility of standard surveillance data streams and will be useful to monitor progress towards and compliance with the 90-90-90 UNAIDS target.
大多数 HIV 感染源自未被诊断且未意识到自身感染的个体。由于对以下两个方面的了解并不完全,因此难以根据监测数据来估算该数量:(i)普通人群中从感染到诊断的时间(TI),以及(ii)外国出生者从移民到诊断的时间。
我们开发了一种新的统计方法,用于根据异质 HIV-1 监测数据的动态建模来估算 HIV-1 的发病率和未被诊断的 HIV 感染者(PLHIV)数量。该方法包括一个使用多个生物标志物的贝叶斯非线性混合效应模型,用于估计 HIV-1 阳性个体的 TI,以及一个新的发病率估计器,该估计器通过明确建模外国出生者是在移民前还是移民后感染的可能性,来区分内源性和外源性感染。该发病率估计器可直接计算未被诊断者的数量。新方法结合了瑞典 2003 年至 2015 年之间的异质监测数据进行说明。
一项留一交叉验证研究表明,多生物标志物模型比单一生物标志物更准确(平均绝对误差为 1.01 比≥1.95)。我们估计,2015 年有 816 名(95%可信区间 775-865)PLHIV 未被诊断,占所有 PLHIV 的 10.8%(95%可信区间 10.3-11.4%)。
所提出的方法将增强标准监测数据流的实用性,并将有助于监测实现和遵守 UNAIDS 90-90-90 目标的进展和合规情况。