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干扰素-γ 诱导蛋白 10(IP-10)作为一种在资源有限环境中优化人类免疫缺陷病毒 RNA 监测的筛查工具。

Interferon-γ-Inducible Protein 10 (IP-10) as a Screening Tool to Optimize Human Immunodeficiency Virus RNA Monitoring in Resource-Limited Settings.

机构信息

ISGlobal, Barcelona Centre for International Health Research, Hospital Clínic-Universitat de Barcelona.

IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol.

出版信息

Clin Infect Dis. 2017 Oct 30;65(10):1670-1675. doi: 10.1093/cid/cix600.

Abstract

BACKGROUND

Achieving effective antiretroviral treatment (ART) monitoring is a key determinant to ensure viral suppression and reach the UNAIDS 90-90-90 targets. The gold standard for detecting virological failure is plasma human immunodeficiency virus (HIV) RNA (viral load [VL]) testing; however, its availability is very limited in low-income countries due to cost and operational constraints.

METHODS

HIV-1-infected adults on first-line ART attending routine visits at the Manhiça District Hospital, Mozambique, were previously evaluated for virologic failure. Plasma levels of interferon-γ-inducible protein 10 (IP-10) were quantified by enzyme-linked immunosorbent assay. Logistic regression was used to build an IP-10-based model able to identify individuals with VL >150 copies/mL. From the 316 individuals analyzed, 253 (80%) were used for model training and 63 (20%) for validation. Receiver operating characteristic curves were employed to evaluate model prediction.

RESULTS

From the individuals included in the training set, 34% had detectable VL. Mean age was 41 years, 70% were females, and median time on ART was 3.4 years. IP-10 levels were significantly higher in subjects with detectable VL (108.2 pg/mL) as compared to those with undetectable VL (38.0 pg/mL) (P < .0001, U test). IP-10 univariate model demonstrated high classification performance (area under the curve = 0.85 [95% confidence interval {CI}, .80-.90]). Using a cutoff value of IP-10 ≥44.2 pg/mL, the model identified detectable VL with 91.9% sensitivity (95% CI, 83.9%-96.7%) and 59.9% specificity (95% CI, 52.0%-67.4%), values confirmed in the validation set.

CONCLUSIONS

IP-10 is an accurate biomarker to screen individuals on ART for detectable viremia. Further studies should evaluate the benefits of IP-10 as a triage approach to monitor ART in resource-limited settings.

摘要

背景

实现有效的抗逆转录病毒治疗 (ART) 监测是确保病毒抑制和达到联合国艾滋病规划署 90-90-90 目标的关键决定因素。检测病毒学失败的金标准是血浆人类免疫缺陷病毒 (HIV) RNA(病毒载量 [VL])检测;然而,由于成本和运营限制,在低收入国家,其可用性非常有限。

方法

莫桑比克马希奇区医院接受一线 ART 治疗的 HIV-1 感染成年人在常规就诊时,先前曾评估过病毒学失败情况。通过酶联免疫吸附试验定量测定干扰素-γ诱导蛋白 10(IP-10)的血浆水平。使用逻辑回归构建能够识别 VL>150 拷贝/mL 的个体的基于 IP-10 的模型。在分析的 316 个人中,253 人(80%)用于模型训练,63 人(20%)用于验证。接收者操作特征曲线用于评估模型预测。

结果

从纳入训练集的个体中,34%的个体可检测到 VL。平均年龄为 41 岁,70%为女性,ART 中位时间为 3.4 年。与不可检测 VL(38.0 pg/mL)相比,可检测 VL(108.2 pg/mL)的个体中 IP-10 水平显著更高(P<0.0001,U 检验)。IP-10 单变量模型显示出较高的分类性能(曲线下面积=0.85[95%置信区间 {CI},0.80-0.90])。使用 IP-10≥44.2 pg/mL 的截止值,该模型以 91.9%的敏感性(95%CI,83.9%-96.7%)和 59.9%的特异性(95%CI,52.0%-67.4%)识别可检测 VL,在验证集中得到了证实。

结论

IP-10 是一种准确的生物标志物,可用于筛选接受 ART 治疗的个体中是否存在可检测的病毒血症。进一步的研究应该评估 IP-10 作为一种资源有限环境中监测 ART 的分诊方法的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e682/5850521/be7ff92abd81/cix60001.jpg

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