Impact of Select Immunologic and Virologic Biomarkers on CD4 Cell Count Decrease in Patients with Chronic HIV-1 Subtype C Infection: Results from Sinikithemba Cohort, Durban, South Africa
Impact of Select Immunologic and Virologic Biomarkers on CD4 Cell Count Decrease in Patients with Chronic HIV-1 Subtype C Infection: Results from Sinikithemba Cohort, Durban, South Africa
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DOI：
10.1086/605503
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发表时间：
2009-09-15
影响因子：
11.8
通讯作者：
Losina, Elena
中科院分区：
文献类型：
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作者：
Brumme, Zabrina;Wang, Bingxia;Losina, Elena
背景。免疫学和临床生物标志物对 1 型人类免疫缺陷病毒 (HIV-1) 感染结果的影响程度尚未完全确定，特别是对于非 B 亚型。根据横断面研究中支持体外 HIV-1 蛋白特异性 CD8 T 淋巴细胞反应与免疫控制相关的数据，我们评估了这些反应以及已建立的 HIV-1 生物标志物与感染 HIV-1 C 亚型个体的 CD4 细胞计数下降率之间的关系。方法。使用双变量和多变量混合效应模型来评估基线 CD4 细胞计数、血浆病毒载量、人类白细胞抗原 (HLA) I 类等位基因和 HIV-1 蛋白特异性 CD8 T 细胞反应与 CD4 细胞计数下降率之间的关系，该队列由 300 名未接受过治疗的慢性感染成人组成，基线 CD4 细胞计数>200 个细胞/mm(3)，血浆病毒载量>500 拷贝/mL。中位随访时间为 25 个月。结果。在双变量分析中，基线 CD4 细胞计数、血浆病毒载量和拥有保护性 HLA 等位基因与 CD4 细胞计数下降率显着相关。 HIV-1 蛋白特异性 CD8 T 细胞反应与 CD4 细胞计数减少之间没有观察到任何关系。纳入基线 CD4 细胞计数（201-350 与 >350 个细胞/mm(3)）、血浆病毒载量（100,000 拷贝/mL）和 HLA（保护性与非保护性）的多变量模型结果能够区分 CD4 细胞计数减少超过 10 倍的范围。在 CD4 细胞计数 >350 个细胞/mm(3) 且血浆病毒载量 >100,000 拷贝/mL、无保护性 HLA 等位基因（每年 -59 个细胞/mm(3)）的个体中观察到下降最快，而在 CD4 细胞计数 201-350 个细胞/mm(3)、血浆病毒载量为 201-350 个细胞/mm(3) 的个体中观察到最慢的下降
Background. The extent to which immunologic and clinical biomarkers influence human immunodeficiency virus type 1 (HIV-1) infection outcomes remains incompletely characterized, particularly for non-B subtypes. On the basis of data supporting in vitro HIV-1 protein-specific CD8 T lymphocyte responses as correlates of immune control in cross-sectional studies, we assessed the relationship of these responses, along with established HIV-1 biomarkers, with rates of CD4 cell count decrease in individuals infected with HIV-1 subtype C.Methods. Bivariate and multivariate mixed-effects models were used to assess the relationship of baseline CD4 cell count, plasma viral load, human leukocyte antigen (HLA) class I alleles, and HIV-1 protein-specific CD8 T cell responses with the rate of CD4 cell count decrease in a longitudinal population-based cohort of 300 therapy-naive, chronically infected adults with baseline CD4 cell counts >200 cells/mm(3) and plasma viral loads > 500 copies/mL over a median of 25 months of follow-up.Results. In bivariate analyses, baseline CD4 cell count, plasma viral load, and possession of a protective HLA allele correlated significantly with the rate of CD4 cell count decrease. No relationship was observed between HIV-1 protein - specific CD8 T cell responses and CD4 cell count decrease. Results from multivariate models incorporating baseline CD4 cell counts (201-350 vs >350 cells/mm(3)), plasma viral load (100,000 copies/mL), and HLA (protective vs not protective) yielded the ability to discriminate CD4 cell count decreases over a 10- fold range. The fastest decrease was observed among individuals with CD4 cell counts >350 cells/mm(3) and plasma viral loads >100,000 copies/mL with no protective HLA alleles (-59 cells/mm(3) per year), whereas the slowest decrease was observed among individuals with CD4 cell counts 201-350 cells/mm(3), plasma viral loads