Mahajan Anish P, Hogan Joseph W, Snyder Brad, Kumarasamy N, Mehta Kalindi, Solomon Suniti, Carpenter Charles C J, Mayer Kenneth H, Flanigan Timothy P
School of Medicine, Brown University, Providence, RI, 02906, USA.
J Acquir Immune Defic Syndr. 2004 May 1;36(1):567-75. doi: 10.1097/00126334-200405010-00004.
A major obstacle to the administration of highly active antiretroviral therapy (HAART) in resource-limited settings is the high cost of CD4 count testing. The total lymphocyte count (TLC) has been proposed as a surrogate marker to monitor immune response to therapy.
To assess, in a developed country setting, the capability and clinical utility of TLC change as a surrogate marker for CD4 count change in monitoring patients on HAART.
Longitudinal co-variation between changes in TLC and concomitant changes in CD4 count following the initiation of HAART was examined using a retrospective cohort study of 126 HIV-positive patients attending The Miriam Hospital, Brown University, Providence, RI. Analyses included evaluation of the direction of TLC change as a marker for direction of CD4 change, using sensitivity and specificity; evaluation of absolute change in TLC as a marker for benchmark changes in CD4 (> or =50 over 6 months, > or =100 over 12 months), using receiver-operator characteristic (ROC) curves; and a regression model of change in TLC as a function of change in CD4, to understand within-individual variation of longitudinal TLC measures.
In the first 24 months of HAART, the sensitivity of a TLC increase as a marker for CD4 count increase over the same time period ranged from 86-94%, and the specificity ranged from 80-85%. The median change in TLC among patients with a CD4 count rise of > or =100 cells/mm at 1 year of HAART was +766 cells/mm while that of patients with a CD4 count rise of <100 cells/m was +100 cells/mm. The area under the corresponding ROC curve was 0.89, suggesting that change in TLC discriminates well between those with 1-year CD4 change of > or =100 vs. those with change <+100. From a regression analysis, we found that mean change in TLC per 1 cell/mm change in CD4 count was 7.3 (SE 1.2, P < 0.001). The degree of this association varied from individual to individual but was positive for all individuals.
Within the first 2 years of HAART, the direction of change in TLC appears to be a strong marker for direction of concomitant change in CD4 count (sensitivity 86-94% and specificity 80-85%, depending on length of interval). Positive and negative predictive values depend on the proportion of CD4 changes that are positive. In this cohort, that proportion is 87.9%, which yields high positive predictive value (96-98%) but lower negative predictive value (43-63%). Findings from the regression model suggest that taking multiple measurements of TLC at more frequent intervals may reduce variability and potentially improve predictive accuracy.
在资源有限的环境中，高效抗逆转录病毒疗法（HAART）给药的一个主要障碍是CD4细胞计数检测成本高昂。总淋巴细胞计数（TLC）已被提议作为监测治疗免疫反应的替代标志物。
在发达国家环境中，评估TLC变化作为HAART治疗患者CD4细胞计数变化替代标志物的能力和临床实用性。
采用回顾性队列研究，对罗德岛普罗维登斯布朗大学米里亚姆医院的126名HIV阳性患者进行研究，检查HAART开始后TLC变化与CD4细胞计数伴随变化之间的纵向协变。分析包括使用敏感性和特异性评估TLC变化方向作为CD4变化方向的标志物；使用受试者工作特征（ROC）曲线评估TLC的绝对变化作为CD4基准变化（6个月内≥50，12个月内≥100）的标志物；以及TLC变化作为CD4变化函数的回归模型，以了解纵向TLC测量的个体内变异。
在HAART治疗的前24个月，TLC升高作为同期CD4细胞计数升高标志物的敏感性范围为86%-94%，特异性范围为80%-85%。HAART治疗1年时CD4细胞计数升高≥100个细胞/mm³的患者中，TLC的中位数变化为+766个细胞/mm³，而CD4细胞计数升高<100个细胞/mm³的患者中，TLC的中位数变化为+100个细胞/mm³。相应ROC曲线下面积为0.89，表明TLC变化能够很好地区分1年CD4变化≥100的患者和变化<+100的患者。通过回归分析，我们发现CD4细胞计数每变化1个细胞/mm³，TLC的平均变化为7.3（标准误1.2，P<0.001）。这种关联程度因人而异，但对所有个体均为正相关。
在HAART治疗的前2年，TLC变化方向似乎是同期CD4细胞计数变化方向的有力标志物（敏感性86%-94%，特异性80%-85%，取决于间隔时间长度）。阳性和阴性预测值取决于CD4变化为阳性的比例。在该队列中，该比例为87.9%，产生高阳性预测值（96%-98%）但较低的阴性预测值（43%-63%）。回归模型的结果表明，更频繁地多次测量TLC可能会降低变异性并潜在提高预测准确性。
