Dubin N, Berman S, Marmor M, Tindall B, Des Jarlais D, Kim M
Department of Environmental Medicine, New York University Medical Center, NY 10016.
Stat Med. 1994 Feb 15;13(3):231-44. doi: 10.1002/sim.4780130306.
We propose a method to estimate the usually unknown time since infection for individuals infected with human immunodeficiency virus type 1 (HIV-1). If we assume the time since infection has an exponential prior distribution, then under the model the conditional distribution of time since infection, given the CD4 level at the time of the first positive HIV-1 antibody test, is a truncated normal density. We applied the method to prevalent cohort data both from intravenous drug users and from homosexual/bisexual men. For the intravenous drug users the estimated mean time since infection was 15.0 months from infection at a presumed mean CD4 level of 1060 cells/ml to first positive antibody test at a CD4 level of 597 cells/ml, which was the average CD4 at enrollment for infected subjects. For the homosexual/bisexual men the estimated mean time since infection was 16.7 months from infection at a presumed mean CD4 level of 699 cells/ml to first positive antibody test at an average CD4 level of 577 cells/ml. We performed a validation study using initially seronegative subjects in these cohorts who seroconverted to HIV-1-positive antibody status during the follow-up period. For the intravenous drug users, data were too few to provide definitive verification of the method. In the cohort of homosexual/bisexual men, however, there was a total of 70 seroconverters with relevant data. Among them, the median absolute difference between the midpoint of the known seroconversion interval and the estimated mean infection date was 4.6 months, conditional on CD4-lymphocyte measurements taken approximately 18 months subsequent to infection. Conditional on CD4 approximately 30 months after infection, this median difference increased modestly to 8.2 months. Our analysis suggested that the underlying mathematical model tends to overestimate short times since infection and underestimate long times since infection. We consider potential corrective modifications to the model.
我们提出了一种方法，用于估计感染了1型人类免疫缺陷病毒（HIV-1）的个体通常未知的感染时间。如果我们假设感染时间具有指数先验分布，那么在该模型下，给定首次HIV-1抗体检测呈阳性时的CD4水平，感染时间的条件分布是一个截断正态密度。我们将该方法应用于来自静脉吸毒者和同性恋/双性恋男性的现患队列数据。对于静脉吸毒者，从假定平均CD4水平为1060个细胞/毫升时感染到CD4水平为597个细胞/毫升时首次抗体检测呈阳性，估计的平均感染时间为15.0个月，这是感染受试者入组时的平均CD4水平。对于同性恋/双性恋男性，从假定平均CD4水平为699个细胞/毫升时感染到平均CD4水平为577个细胞/毫升时首次抗体检测呈阳性，估计的平均感染时间为16.7个月。我们使用这些队列中最初血清学阴性且在随访期间血清转化为HIV-1阳性抗体状态的受试者进行了一项验证研究。对于静脉吸毒者，数据太少，无法对该方法进行明确验证。然而，在同性恋/双性恋男性队列中，共有70名血清转化者有相关数据。其中，已知血清转化间隔中点与估计平均感染日期之间的中位数绝对差异为4.6个月，条件是在感染后约18个月进行CD4淋巴细胞测量。在感染后约30个月进行CD4测量的条件下，该中位数差异适度增加至8.2个月。我们的分析表明，潜在的数学模型往往会高估感染后的短时间，而低估感染后的长时间。我们考虑对该模型进行潜在的校正修改。
