CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals.
CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals.
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DOI：
10.1371/journal.pone.0003165
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发表时间：
2008-09-08
期刊：
影响因子：
3.7
通讯作者：
Ahuja SK
中科院分区：
文献类型：
--
作者：
Kulkarni H;Agan BK;Marconi VC;O'Connell RJ;Camargo JF;He W;Delmar J;Phelps KR;Crawford G;Clark RA;Dolan MJ;Ahuja SK
目前尚不清楚基因组学的最新进展是否能部分解决令人烦恼的临床决策困境。例如，在HIV-1感染期间何时开始高效抗逆转录病毒疗法（HAART）仍然是临床难题。这一决定在很大程度上依赖于基于CD 4 + T细胞计数和血浆病毒载量的艾滋病风险评估。然而，这两个实验室标志物的轨迹的影响，在一定程度上，在CCR 5，主要的HIV辅助受体，和CCL 3L 1，一个有效的CCR 5配体和HIV抑制趋化因子的基因拷贝数的多态性。因此，我们确定是否同时考虑遗传和实验室标记物提供了一种评估艾滋病风险的改进方法。在一个由1，132名艾滋病毒阳性受试者组成的前瞻性、单一地点、种族混合队列中，我们分别和联合确定了实验室和遗传标记传达的艾滋病风险。根据CCL 3L 1和CCR 5的变异，受试者被分配到低、中或高遗传风险组（GRG）。根据似然比估计，CCL 3L 1-CCR 5 GRG的预测值与实验室标志物的预测值相当。当实验室标志物表达相反的风险时，GRG状态也预测了艾滋病的发展。此外，在来自自然史队列的两个独立的大组HIV+受试者中，加性风险评分系统和分类回归树（CART）分析的结果显示，实验室和CCL 3L 1-CCR 5遗传标记一起提供的预后信息比单独使用任何一种标记都多。此外，GRG独立预测从血清转换到用于指导HAART启动的CD 4+细胞计数阈值的时间间隔。实验室和遗传标记的结合比单独的标记捕获了更广泛的艾滋病风险。通过追踪艾滋病风险的一个独特方面，与实验室参数所捕获的不同，CCL 3L 1-CCR 5基因型可能在HIV临床管理中具有实用性。这些发现说明了基因组信息如何应用于实现个性化医疗的实际效益。
Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART) during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4+ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk. In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG) based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV+ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART) analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4+ cell count thresholds used to guide HAART initiation. The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters, CCL3L1-CCR5 genotypes may have utility in HIV clinical management. These findings illustrate how genomic information might be applied to achieve practical benefits of personalized medicine.
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影响因子：
5.4
作者：
Hladik, F;Liu, HL;McElrath, MJ
通讯作者：
McElrath, MJ
影响因子：
82.9
作者：
Ahuja, Sunil K.;Kulkarni, Hemant;Dolan, Matthew J.
通讯作者：
Dolan, Matthew J.
影响因子：
56.9
作者：
Gonzalez, E;Kulkarni, H;Ahuja, SK
通讯作者：
Ahuja, SK
影响因子：
56.9
作者：
Gibbs, Richard A.;Rogers, Jeffrey;Zwieg, Ann S.
通讯作者：
Zwieg, Ann S.
DOI：
10.1073/pnas.2035075100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Abdelwahab, SF;Cocchi, F;Lewis, GK
通讯作者：
Lewis, GK