CD4+ cell dynamics in untreated HIV-1 infection: overall rates, and effects of age, viral load, sex and calendar time.
CD4+ cell dynamics in untreated HIV-1 infection: overall rates, and effects of age, viral load, sex and calendar time.
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未经治疗的 HIV-1 感染中的 CD4+ 细胞动态：总体比率以及年龄、病毒载量、性别和日历时间的影响。
DOI：
10.1097/qad.0000000000000854
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发表时间：
2015-11-28
期刊：
影响因子：
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通讯作者：
Fraser C
中科院分区：
文献类型：
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作者：
Cori A;Pickles M;van Sighem A;Gras L;Bezemer D;Reiss P;Fraser C
CD4+细胞计数是衡量艾滋病毒疾病进展的关键指标，也是开始治疗的连续国际指南的基础。CD4+细胞动力学用于评估公共卫生需求和干预措施的数学和计量模型。在这里，我们估计CD4+下降率，通过相关协变量分层，以临床透明的形式，可直接用于此类模型。我们分析了荷兰队列的艾滋病治疗评估，包括血清转化日期估计在1年内的个体，以及治疗开始前的强化临床随访。由于CD4+细胞计数本质上是嘈杂的，我们将分析分为平滑CD4+细胞计数的长期趋势和实际CD4+测量与潜在平滑计数相关的观察模型。我们使用单调样条平滑模型来描述平滑后CD4+细胞计数的下降，分为CD4+高于500、350-500、200 - 350和200细胞/μl或更低。我们估计了在血清转换后从每个类别开始的个体的比例以及在每个类别中花费的平均时间。我们检查影响这些参数的个人水平的辅助因素。在未治疗的个体中，每个隔间的时间分别为3.32年、2.70年、5.50年和5.06年。血清转化后CD4+细胞计数高于500个/μl室的仅76%。设定点病毒载量（SPVL）是一个重要因素：至少5 log10拷贝/ml的个体需要5.37年才能达到CD4+细胞计数低于200个细胞/μl，而SPVL低于4 log10拷贝/ml的个体需要15.76年。许多个体经血清转化后CD4+细胞计数已低于500个/μl。SPVL强烈影响CD4+下降速率。治疗指南应考虑测量SPVL，而数学模型应纳入SPVL分层。
CD4+ cell count is a key measure of HIV disease progression, and the basis of successive international guidelines for treatment initiation. CD4+ cell dynamics are used in mathematical and econometric models for evaluating public health need and interventions. Here, we estimate rates of CD4+ decline, stratified by relevant covariates, in a form that is clinically transparent and can be directly used in such models. We analyse the AIDS Therapy Evaluation in the Netherlands cohort, including individuals with date of seroconversion estimated to be within 1 year and with intensive clinical follow-up prior to treatment initiation. Owing to the fact that CD4+ cell counts are intrinsically noisy, we separate the analysis into long-term trends of smoothed CD4+ cell counts and an observation model relating actual CD4+ measurements to the underlying smoothed counts. We use a monotonic spline smoothing model to describe the decline of smoothed CD4+ cell counts through categories CD4+ above 500, 350–500, 200–350 and 200 cells/μl or less. We estimate the proportion of individuals starting in each category after seroconversion and the average time spent in each category. We examine individual-level cofactors which influence these parameters. Among untreated individuals, the time spent in each compartment was 3.32, 2.70, 5.50 and 5.06 years. Only 76% started in the CD4+ cell count above 500 cells/μl compartment after seroconversion. Set-point viral load (SPVL) was an important factor: individuals with at least 5 log10 copies/ml took 5.37 years to reach CD4+ cell count less than 200 cells/μl compared with 15.76 years for SPVL less than 4 log10 copies/ml. Many individuals already have CD4+ cell count below 500 cells/μl after seroconversion. SPVL strongly influences the rate of CD4+ decline. Treatment guidelines should consider measuring SPVL, whereas mathematical models should incorporate SPVL stratification.