Liang Hua, Wu Hulin, Carroll Raymond J
Department of Biostatistics, St. Jude Children's Research Hospital, 332 North Lauderdale St., Memphis, TN 38105, USA.
Biostatistics. 2003 Apr;4(2):297-312. doi: 10.1093/biostatistics/4.2.297.
In this article we study the relationship between virologic and immunologic responses in AIDS clinical trials. Since plasma HIV RNA copies (viral load) and CD4+ cell counts are crucial virologic and immunologic markers for HIV infection, it is important to study their relationship during HIV/AIDS treatment. We propose a mixed-effects varying-coefficient model based on an exploratory analysis of data from a clinical trial. Since both viral load and CD4+ cell counts are subject to measurement error, we also consider the measurement error problem in covariates in our model. The regression spline method is proposed for inference for parameters in the proposed model. The regression spline method transforms the unknown nonparametric components into parametric functions. It is relatively simple to implement using readily available software, and parameter inference can be developed from standard parametric models. We apply the proposed models and methods to an AIDS clinical study. From this study, we find an interesting relationship between viral load and CD4+ cell counts during antiviral treatments. Biological interpretations and clinical implications are discussed.
在本文中，我们研究了艾滋病临床试验中病毒学反应与免疫学反应之间的关系。由于血浆HIV RNA拷贝数（病毒载量）和CD4+细胞计数是HIV感染关键的病毒学和免疫学标志物，因此在HIV/AIDS治疗期间研究它们之间的关系很重要。基于对一项临床试验数据的探索性分析，我们提出了一个混合效应变系数模型。由于病毒载量和CD4+细胞计数都存在测量误差，我们在模型中还考虑了协变量中的测量误差问题。针对所提出模型中的参数推断，我们提出了回归样条方法。回归样条方法将未知的非参数成分转化为参数函数。使用现成的软件实施相对简单，并且可以从标准参数模型进行参数推断。我们将所提出的模型和方法应用于一项艾滋病临床研究。从这项研究中，我们发现了抗病毒治疗期间病毒载量与CD4+细胞计数之间的有趣关系。我们还讨论了生物学解释和临床意义。
