抗原尿预测内脏利什曼病/艾滋病毒合并感染患者初始治疗失败和复发:埃塞俄比亚临床试验中的一项嵌套探索性研究。

Antigenuria to Predict Initial Treatment Failure and Relapse in Visceral Leishmaniasis/HIV Coinfected Patients: An Exploratory Study Nested Within a Clinical Trial in Ethiopia.

机构信息

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Department of Clinical Sciences, University of Gondar, Gondar, Ethiopia.

出版信息

Front Cell Infect Microbiol. 2018 Mar 29;8:94. doi: 10.3389/fcimb.2018.00094. eCollection 2018.

Abstract

Biomarkers predicting the risk of VL treatment failure and relapse in VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1) levels of antigenuria measured at VL diagnosis were associated with initial treatment failure and (2) levels of antigenuria at the end of treatment (parasitologically-confirmed cure) were associated with subsequent relapse. antigenuria at VL diagnosis and cure was determined using KAtex urine antigen test and graded as negative (0), weak/moderate (grade 1+/2+) or strongly-positive (3+). Logistic regression and Kaplan-Meier methods were used to assess the association between antigenuria and (1) initial treatment failure, and (2) relapse over the 12 months after cure, respectively. The analysis to predict initial treatment failure included sixty-three coinfected adults [median age: 30 years interquartile range (IQR) 27-35], median CD4 count: 56 cells/μL (IQR 38-113). KAtex results at VL diagnosis were negative in 11 (17%), weak/moderate in 17 (27%) and strongly-positive in 35 (36%). Twenty (32%) patients had parasitologically-confirmed treatment failure, with a risk of failure of 9% (1/11) with KAtex-negative results, 0% (0/17) for KAtex 1+/2+ and 54% (19/35) for KAtex 3+ results. Compared to KAtex-negative patients, KAtex 3+ patients were at increased risk of treatment failure [odds ratio 11.9 (95% CI 1.4-103.0); : 0.025]. Forty-four patients were included in the analysis to predict relapse [median age: 31 years (IQR 28-35), median CD4 count: 116 cells/μL (IQR 95-181)]. When achieving VL cure, KAtex results were negative in 19 (43%), weak/moderate (1+/2+) in 10 (23%), and strongly positive (3+) in 15 patients (34%). Over the subsequent 12 months, eight out of 44 patients (18%) relapsed. The predicted 1-year relapse risk was 6% for KAtex-negative results, 14% for KAtex 1+/2+ and 42% for KAtex 3+ results [hazard ratio of 2.2 (95% CI 0.1-34.9) for KAtex 1+/2+ and 9.8 (95% CI 1.8-82.1) for KAtex 3+, compared to KAtex negative patients; : 0.03]. A simple field-deployable urine antigen test can be used for risk stratification of initial treatment failure and VL relapse in HIV-patients. A dipstick-format would facilitate field implementation.

摘要

在 HIV 合并利什曼病(VL)患者中,需要能够预测治疗失败和复发风险的生物标志物。在埃塞俄比亚的一个两站点临床试验(2011-2015 年)中,我们进行了一项探索性研究,以评估以下两种情况:(1)在 VL 诊断时测量的抗原尿水平是否与初始治疗失败相关;(2)治疗结束时(寄生虫学确认治愈)的抗原尿水平是否与随后的复发相关。使用 KAtex 尿液抗原检测法来确定抗原尿的水平,结果分为阴性(0)、弱阳性/中度阳性(1+/2+)或强阳性(3+)。采用逻辑回归和 Kaplan-Meier 方法评估抗原尿与(1)初始治疗失败和(2)治疗结束后 12 个月内复发之间的关联。预测初始治疗失败的分析包括 63 例合并感染的成年人[中位年龄:30 岁,四分位间距(IQR)27-35],中位 CD4 计数为 56 个/μL(IQR 38-113)。VL 诊断时 KAtex 结果阴性者 11 例(17%),弱阳性/中度阳性者 17 例(27%),强阳性者 35 例(36%)。20 例(32%)患者经寄生虫学确认治疗失败,KAtex 阴性结果的失败风险为 9%(1/11),KAtex 1+/2+的失败风险为 0%(0/17),KAtex 3+的失败风险为 54%(19/35)。与 KAtex 阴性患者相比,KAtex 3+患者治疗失败的风险更高[比值比 11.9(95%CI 1.4-103.0);:0.025]。44 例患者纳入预测复发的分析[中位年龄:31 岁(IQR 28-35),中位 CD4 计数:116 个/μL(IQR 95-181)]。当达到 VL 治愈时,KAtex 结果阴性者 19 例(43%),弱阳性/中度阳性者 10 例(23%),强阳性者 15 例(34%)。在随后的 12 个月内,44 例患者中有 8 例(18%)复发。KAtex 阴性结果的 1 年复发风险为 6%,KAtex 1+/2+的为 14%,KAtex 3+的为 42%[KAtex 1+/2+的风险比(HR)为 2.2(95%CI 0.1-34.9),KAtex 3+的为 9.8(95%CI 1.8-82.1),与 KAtex 阴性患者相比;:0.03]。一种简单的现场可部署尿液抗原检测方法可用于 HIV 患者的初始治疗失败和 VL 复发的风险分层。一种条带式格式将有助于现场实施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7389/5884955/03421b65dfc9/fcimb-08-00094-g0001.jpg

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