Plasma viral load and CD4(+) lymphocytes as prognostic markers of HIV-1 infection

Plasma viral load and CD4(+) lymphocytes as prognostic markers of HIV-1 infection
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DOI:
10.7326/0003-4819-126-12-199706150-00003
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发表时间:
1997-06-15
影响因子:
39.2
通讯作者:
Rinaldo, CR
Rinaldo, CR
中科院分区:
医学1区
文献类型:
--
作者:
Mellors, JW;Munoz, A;Rinaldo, CR

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工作背景:人类免疫缺陷病毒1型(HIV-1)感染者的疾病进展率差异很大,疾病活动性标志物的相对预后价值尚未确定。目的:比较临床、血清学、细胞学和病毒学标志物预测10年内获得性免疫缺陷综合征(AIDS)进展和死亡的能力。设计:前瞻性、多中心队列研究。设置:参与多中心艾滋病队列研究的四所大学的临床中心。患者:1604名HIV-1感染的男性。测量:比较的标志物为口腔念珠菌病(鹅口疮)或发热;血清新蝶呤水平;血清β(2)-微球蛋白水平; CD 3(+)、CD 4(+)和CD 8(+)淋巴细胞的数量和百分比;以及血浆病毒载量,其测量为使用灵敏的分支DNA信号放大测定法发现的HIV-1 RNA的浓度。血浆病毒载量是艾滋病进展和死亡的最佳预测因子,(按预测强度排序)通过CD 4(+)淋巴细胞计数和血清新蝶呤水平、血清β(2)-微球蛋白水平和鹅口疮或发热。血浆病毒载量可区分所有水平的CD 4(+)淋巴细胞计数的风险,并预测其随后的下降率。根据血浆HIV-1 RNA浓度定义了5种风险类别:500拷贝/mL或更低、501至3000拷贝/mL、3001至10 000拷贝/mL、10 001至30 000拷贝/mL和超过30 000拷贝/mL。在5个风险类别中,6年内进展为艾滋病的参与者百分比差异非常显著(P < 0.001):分别为5.4%、16.6%、31.7%、55.2%和80.0%。6年内死于艾滋病的受试者百分比在5个风险类别中也有高度显著性差异(P < 0.001):分别为0.9%、6.3%、18.1%、34.9%和69.5%。结合HIV-1 RNA测量和CD 4(+)淋巴细胞计数的回归树比单独使用任何一种标记物提供了更好的结果区分;使用这两个变量定义了6是的内艾滋病风险的类别,范围从小于2%到98%。血浆病毒载量强有力地预测了CD 4(+)淋巴细胞计数的下降率以及进展为AIDS和死亡,但联合检测血浆HIV-1 RNA和CD 4(+)淋巴细胞可更准确地判断HIV感染者的预后。
Background: The rate of disease progression among persons infected with human immunodeficiency virus type 1 (HIV-1) varies widely, and the relative prognostic value of markers of disease activity has not been defined.Objective: To compare clinical, serologic, cellular, and virologic markers for their ability to predict progression to the acquired immunodeficiency syndrome (AIDS) and death during a 10-year period.Design: Prospective, multicenter cohort study.Setting: Four university-based clinical centers participating in the Multicenter AIDS Cohort Study.Patients: 1604 men infected with HIV-1.Measurements: The markers compared were oral candidiasis (thrush) or fever; serum neopterin levels; serum beta(2)-microglobulin levels; number and percentage of CD3(+), CD4(+), and CD8(+) lymphocytes; and plasma viral load, which was measured as the concentration of HIV-1 RNA found using a sensitive branched-DNA signal-amplification assay.Results: Plasma viral load was the single best predictor of progression to AIDS and death, followed (in order of predictive strength) by CD4(+) lymphocyte count and serum neopterin levels, serum beta(2)-microglobulin levels, and thrush or fever. Plasma viral load discriminated risk at all levels of CD4(+) lymphocyte counts and predicted their subsequent rate of decline. Five risk categories were defined by plasma HIV-l RNA concentrations: 500 copies/mL or less, 501 to 3000 copies/mL, 3001 to 10 000 copies/mL, 10 001 to 30 000 copies/mL, and more than 30 000 copies/mL. Highly significant (P < 0.001) differences in the percentages of participants who progressed to AIDS within 6 years were seen in the five risk categories: 5.4%, 16.6%, 31.7%, 55.2%, and 80.0%, respectively. Highly significant (P < 0.001) differences in the percentages of participants who died of AIDS within 6 years were also seen in the five risk categories: 0.9%, 6.3%, 18.1%, 34.9%, and 69.5%, respectively. A regression tree incorporating both HIV-1 RNA measurements and CD4(+) lymphocyte counts provided better discrimination of outcome than did either marker alone; use of both variables defined categories of risk for AIDS within 6 yea rs that ranged from less than 2% to 98%.Conclusions: Plasma viral load strongly predicts the rate of decrease in CD4(+) lymphocyte count and progression to AIDS and death, but the prognosis of HIV-infected persons is more accurately defined by combined measurement of plasma HIV-1 RNA and CD4(+) lymphocytes.