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.
J Antimicrob Chemother. 2018 Dec 1;73(12):3460-3470. doi: 10.1093/jac/dky350.
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.
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.
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).
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).
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。
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。
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）。
抗逆转录病毒治疗前 HIV DNA 与 HIV RNA 和 CD4+T 细胞计数一起，应被视为一种新的分期标志物，以更好地识别那些在实现病毒学抑制（≤50 拷贝/ml）后病毒反弹风险较低（或较高）的人群。
