一线抗逆转录病毒治疗（ART）前 HIV-1 脱氧核糖核酸（DNA）与 CD4+ T 细胞中基线病毒学-免疫学状态和结局相关。

Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline viro-immunological status and outcome in patients under first-line ART.

机构信息

Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.

Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME) Institute for Global Health, UCL, London, UK.

出版信息

J Antimicrob Chemother. 2018 Dec 1;73(12):3460-3470. doi: 10.1093/jac/dky350.

DOI:10.1093/jac/dky350

PMID:30247724

Abstract

OBJECTIVES

We evaluated the association between pre-ART HIV DNA and HIV-infected participant characteristics at baseline as well as with their response to first-line ART.

METHODS

Four hundred and thirty-three patients from the ICONA cohort, starting first-line ART after the year 2000, were analysed. Pre-ART HIV DNA was quantified with the modified COBAS TaqMan HIV-1 Test and normalized by CD4+ T cells. Linear correlation between pre-ART HIV DNA and other continuous markers (HIV RNA, CD4 count, markers of inflammation and coagulation) at baseline was evaluated by means of Pearson correlation coefficient and a linear regression model. Survival analyses and Cox regression models were used to study the association between pre-ART HIV DNA and time to viro-immunoclinical events.

RESULTS

Pre-ART HIV DNA [median (IQR): 10 702 (3397-36 632) copies/106 CD4+ T cells] was correlated with pre-ART HIV RNA [R2 = +0.44, (P < 0.0001)], CD4+ T cells [R2 = -0.58, (P < 0.0001)] and CD4/CD8 ratio [R2 = -0.48, (P < 0.0001)], while weaker correlations were observed with CD8+ T cells (R2 = -0.20, P = 0.01), IL-6 (R2 = +0.16, P = 0.002) and soluble CD14 (R2 = +0.09, P = 0.05). Patients with higher pre-ART HIV DNA showed lower rate and delayed virological response (defined as HIV RNA ≤50 copies/mL), compared with those having lower HIV DNA (67.2% for >10 000, 81.1% for 1000-10 000 and 86.4% for 10-1000 copies/106 CD4+ T cells; P = 0.0004). Higher pre-ART HIV DNA was also correlated with increased risk of virological rebound (defined as HIV RNA >50 copies/mL) by 24 months (17.2% for >10 000, 7.4% for 1000-10 000 and 4.3% for 10-1000 copies/106 CD4+ T cells; P = 0.0048). Adjusted HRs of all virological rebound definitions confirmed these findings (P ≤ 0.02).

CONCLUSIONS

Pre-ART HIV DNA, along with HIV RNA and CD4+ T cell count, should be considered as a new staging marker to better identify people at lower (or higher) risk of viral rebound following achievement of virological suppression (≤50 copies/mL).

摘要

目的

我们评估了基线时抗逆转录病毒治疗（ART）前 HIV DNA 与 HIV 感染参与者特征之间的关联，以及它们与一线 ART 反应之间的关联。

方法

分析了 ICONA 队列中的 433 名患者，他们在 2000 年后开始接受一线 ART。使用改良的 COBAS TaqMan HIV-1 检测定量检测抗逆转录病毒治疗前 HIV DNA，并通过 CD4+T 细胞进行标准化。采用 Pearson 相关系数和线性回归模型评估抗逆转录病毒治疗前 HIV DNA 与其他连续标志物（HIV RNA、CD4 计数、炎症和凝血标志物）之间的线性相关性。生存分析和 Cox 回归模型用于研究抗逆转录病毒治疗前 HIV DNA 与病毒免疫临床事件之间的关系。

结果

抗逆转录病毒治疗前 HIV DNA[中位数（IQR）：10702（3397-36632）拷贝/106 CD4+T 细胞]与抗逆转录病毒治疗前 HIV RNA [R2=+0.44，（P<0.0001）]、CD4+T 细胞[R2=-0.58，（P<0.0001）]和 CD4/CD8 比值[R2=-0.48，（P<0.0001）]相关，而与 CD8+T 细胞（R2=-0.20，P=0.01）、白细胞介素-6（R2=+0.16，P=0.002）和可溶性 CD14（R2=+0.09，P=0.05）的相关性较弱。与 HIV DNA 较低的患者相比，抗逆转录病毒治疗前 HIV DNA 较高的患者的病毒学反应率和延迟较低（定义为 HIV RNA≤50 拷贝/ml）（>10000 拷贝/ml 的为 67.2%，1000-10000 拷贝/ml 的为 81.1%，10-1000 拷贝/ml 的为 86.4%；P=0.0004）。较高的抗逆转录病毒治疗前 HIV DNA 也与 24 个月时病毒学反弹（定义为 HIV RNA>50 拷贝/ml）的风险增加相关（>10000 拷贝/ml 的为 17.2%，1000-10000 拷贝/ml 的为 7.4%，10-1000 拷贝/ml 的为 4.3%；P=0.0048）。所有病毒学反弹定义的调整后 HR 均证实了这些发现（P≤0.02）。