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Trends of HIV-1 incidence with credible intervals in Sweden 2002–09 reconstructed using a dynamic model of within-patient IgG growth

机译:使用住院患者中IgG增长的动态模型重建了瑞典2002-09年HIV-1发病率趋势的可信区间

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摘要

>Background: HIV-1 is a lifelong disease, often without serious symptoms for years after infection, and thus many infected persons go undetected for a long time. This makes it difficult to track incidence, and thus epidemics may go through dramatic changes largely unnoticed, only to be detected years later. Because direct measurement of incidence is expensive and difficult, several biomarker-based tests and algorithms have been developed to distinguish between recent and long-term infections. However, current methods have been criticized and demands for novel methods have been raised.>Methods: We developed and applied a biomarker-based incidence model, joining a time-continuous model of immunoglobulin G (IgG) growth (measured by the IgG-capture BED-enzyme immunoassay) with statistical corrections for both sample size and unobserved diagnoses. Our method uses measurements of IgG concentration in newly diagnosed people to calculate the posterior distribution of infection times. Time from infection to diagnosis is modelled for all individuals in a given period and is used to calculate a sample weight to correct for undiagnosed individuals. We then used a bootstrapping method to reconstruct point estimates and credible intervals of the incidence of HIV-1 in Sweden based on a sample of newly diagnosed people.>Results: We found evidence for: (i) a slowly but steadily increasing trend in both the incidence and incidence rate in Sweden; and (ii) an increasing but well-controlled epidemic in gay men in Stockholm. Sensitivity analyses showed that our method was robust to realistic levels (up to 15%) of BED misclassification of non-recently infected persons as early infections.>Conclusions: We developed a novel incidence estimator based on previously published theoretical work that has the potential to provide rapid, up-to-date estimates of HIV-1 incidence in populations where BED test data are available.
机译:>背景: HIV-1是一生的疾病,感染后数年通常没有严重的症状,因此许多感染者长期未被发现。这使得很难跟踪发病率,因此流行病可能会经历戏剧性的变化,而这种变化在很大程度上未被注意到,只有在几年后才被发现。由于直接测量发病率既昂贵又困难,因此已经开发了几种基于生物标志物的测试和算法来区分近期感染和长期感染。但是,当前的方法遭到了批评,并且对新颖方法提出了更高的要求。>方法:我们开发并应用了基于生物标志物的发病模型,并加入了免疫球蛋白G(IgG)生长的时间连续模型(通过IgG捕获BED酶免疫测定法进行检测),并对样本量和未观察到的诊断均进行统计校正。我们的方法使用新诊断人群中IgG浓度的测量值来计算感染时间的后验分布。从感染到诊断的时间在给定时间内针对所有个体建模,并用于计算样本权重以校正未诊断的个体。然后,我们根据新近诊断出的人群样本,采用自举法重建了瑞典HIV-1感染的点估计值和可信区间。>结果:我们发现了以下证据:(i)但是瑞典的发病率和发病率均呈稳定增长趋势; (ii)斯德哥尔摩男同性恋者的流行在不断增加,但控制得当。敏感性分析表明,我们的方法对于非近期感染者的BED错误分类为实际水平(高达15%)具有较强的鲁棒性。>结论:我们根据先前发表的理论开发了一种新颖的发病率估算器有可能提供BED测试数据的人群中HIV-1发病率的快速,最新估计的工作。

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