针对预防试验的艾滋病毒感染日期的贝叶斯估计
Raabya Rossenkhan1, Elena E Giorgi1, Danica Shao1
1Fred Hutchinson Cancer Center, Vaccine and Infectious Disease Division, Seattle, Washington, USA.
mBio
|September 9, 2025
概括
在预防试验中,准确估计HIV感染时间至关重要. 结合诊断和病毒序列数据的新贝叶斯管道显著改善了时间估计,在采集后5周内使用样本时偏差更小.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 生物统计学 生物统计学
背景情况:
- 准确估计艾滋病毒感染时间对于艾滋病毒预防试验至关重要,以确定感染时的抗体水平.
- 抗体介导预防 (AMP) 研究表明,广泛中和抗体在预防艾滋病毒感染方面具有有效性.
研究的目的:
- 利用诊断和病毒序列数据,开发和评估一个用于估计可检测HIV感染日期 (DDA) 的管道.
- 提高艾滋病毒预防试验参与者的艾滋病毒感染时间估计的准确性.
主要方法:
- 开发了一个贝叶斯策略,结合了REN序列,GP序列和诊断数据流.
- 使用PacBio病毒序列数据评估管道的性能,这些数据来自FRESH和RV217急性HIV感染队列研究中的41名参与者.
- 定义"真实DDA"为最后一个负的和第一个阳性的RNA诊断测试之间的中点.
主要成果:
- 仅仅诊断数据就导致偏差为2.4天,RMSE为7.9天.
- 结合序列和诊断数据改善了估计 (偏差1.5天,RMSE6.9天).
- 将基于序列的估计限制在DDA后5周内的样本上,进一步将偏差减少到0.2天 (RMSE 7.8天).
结论:
- 开发的管道提高了艾滋病毒获取时间估计的准确性.
- 基于序列的估计,特别是在DDA后5周内采集的样本,提供了更好的精度.
- 建议在未来的临床试验中使用基于序列的获取时间估计的月度采样频率.
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