Stichting HIV Monitoring, Amsterdam, The Netherlands.
PLoS One. 2013 May 27;8(5):e64437. doi: 10.1371/journal.pone.0064437. Print 2013.
Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.
Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART, <100 CD4 cells/mm³, or AIDS) among therapy-naïve MSM HIV-1 seroconverters in the Netherlands. These models make different assumptions about the censoring process.
All 3 models estimated lower median CD4 cell counts 9 months after seroconversion in later calendar years (623, 582, and 541 cells/mm³ for 1984-1995 [n = 111], 1996-2002 [n = 139], and 2003-2007 seroconverters [n = 356], respectively, shared-parameter model). Only the 2 joint-models found a trend for a steeper decline of CD4 cell counts with seroconversion in later calendar years (overall p-values 0.002 and 0.06 for the pattern-mixture and the shared-parameter model, respectively). In the shared-parameter model the median decline from 9 to 48 months was 276 cellsmm³ for 1984-1995 seroconverters and 308 cells/mm³ for 2003-2007 seroconverters (difference in slope, p = 0.045).
Mixed-effects models underestimate the CD4 cell decline prior to starting ART. Joint-models suggest that CD4 cell count declines more rapidly in patients infected between 2003 and 2007 compared to patients infected before 1996.
研究表明，如果不进行治疗，荷兰的 HIV-1 流行可能变得更加致命，导致疾病更快进展。分析未经抗逆转录病毒治疗（ART）启动前 CD4 细胞计数的下降，作为疾病进展的替代标志物，可能会因信息性删失而受到阻碍，因为随着 CD4 细胞计数下降更为陡峭，更有可能开始 ART。
使用混合效应模型和 2 种联合模型分析了从血清转换后 9 至 48 个月的 CD4 细胞计数，这些模型共同对荷兰未经 ART 治疗的男男性行为者 HIV-1 血清转换者的 CD4 细胞计数和删失事件（开始 ART、<100 CD4 细胞/mm³或 AIDS）时间进行建模。这些模型对删失过程有不同的假设。
所有 3 种模型均估计，在更晚的日历年内，血清转换后 9 个月时的中位 CD4 细胞计数较低（1984-1995 年（n = 111）、1996-2002 年（n = 139）和 2003-2007 年血清转换者（n = 356）的中位 CD4 细胞计数分别为 623、582 和 541 个细胞/mm³），共享参数模型）。只有 2 个联合模型发现了 CD4 细胞计数随着更晚的日历年内血清转换而更陡峭下降的趋势（整体 p 值分别为 0.002 和 0.06，模式混合模型和共享参数模型）。在共享参数模型中，从 9 到 48 个月的中位数下降为 1984-1995 年血清转换者的 276 个细胞/mm³和 2003-2007 年血清转换者的 308 个细胞/mm³（斜率差异，p = 0.045）。
混合效应模型低估了开始 ART 前的 CD4 细胞下降。联合模型表明，与 1996 年之前感染的患者相比，2003 年至 2007 年感染的患者的 CD4 细胞计数下降更快。
