Shanks Leslie, Siddiqui M Ruby, Abebe Almaz, Piriou Erwan, Pearce Neil, Ariti Cono, Masiga Johnson, Muluneh Libsework, Wazome Joseph, Ritmeijer Koert, Klarkowski Derryck
Médecins Sans Frontières, Amsterdam, The Netherlands.
Médecins Sans Frontières, London, UK.
Virol J. 2015 May 14;12:75. doi: 10.1186/s12985-015-0306-4.
Current WHO testing guidelines for resource limited settings diagnose HIV on the basis of screening tests without a confirmation test due to cost constraints. This leads to a potential risk of false positive HIV diagnosis. In this paper, we evaluate the dilution test, a novel method for confirmation testing, which is simple, rapid, and low cost. The principle of the dilution test is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the sample, in order to screen out the cross reacting antibodies responsible for falsely positive RDT results.
Participants were recruited from two testing centres in Ethiopia where a tiebreaker algorithm using 3 different RDTs in series is used to diagnose HIV. All samples positive on the initial screening RDT and every 10th negative sample underwent testing with the gold standard and dilution test. Dilution testing was performed using Determine™ rapid diagnostic test at 6 different dilutions. Results were compared to the gold standard of Western Blot; where Western Blot was indeterminate, PCR testing determined the final result.
2895 samples were recruited to the study. 247 were positive for a prevalence of 8.5 % (247/2895). A total of 495 samples underwent dilution testing. The RDT diagnostic algorithm misclassified 18 samples as positive. Dilution at the level of 1/160 was able to correctly identify all these 18 false positives, but at a cost of a single false negative result (sensitivity 99.6 %, 95 % CI 97.8-100; specificity 100 %, 95 % CI: 98.5-100). Concordance between the gold standard and the 1/160 dilution strength was 99.8 %.
This study provides proof of concept for a new, low cost method of confirming HIV diagnosis in resource-limited settings. It has potential for use as a supplementary test in a confirmatory algorithm, whereby double positive RDT results undergo dilution testing, with positive results confirming HIV infection. Negative results require nucleic acid testing to rule out false negative results due to seroconversion or misclassification by the lower sensitivity dilution test. Further research is needed to determine if these results can be replicated in other settings.
ClinicalTrials.gov, NCT01716299 .
由于成本限制，世界卫生组织当前针对资源有限环境的检测指南基于筛查试验诊断HIV，而不进行确认试验。这导致HIV诊断出现假阳性的潜在风险。在本文中，我们评估了稀释试验，这是一种用于确认试验的新方法，它简单、快速且成本低。稀释试验的原理是通过稀释样本改变快速诊断试验（RDT）的灵敏度，以筛选出导致RDT结果假阳性的交叉反应抗体。
从埃塞俄比亚的两个检测中心招募参与者，在这些中心使用一种串联使用3种不同RDT的决胜算法来诊断HIV。所有初始筛查RDT呈阳性的样本以及每第10个阴性样本都接受了金标准检测和稀释试验。使用Determine™快速诊断试验在6种不同稀释度下进行稀释试验。将结果与免疫印迹金标准进行比较；当免疫印迹结果不确定时，通过PCR检测确定最终结果。
共招募了2895个样本进行研究。其中247个呈阳性，患病率为8.5%（247/2895）。共有495个样本进行了稀释试验。RDT诊断算法将18个样本误分类为阳性。1/160稀释度能够正确识别所有这18例假阳性，但代价是出现1例假阴性结果（灵敏度99.6%，95%置信区间97.8 - 100；特异性100%，95%置信区间：98.5 - 100）。金标准与1/160稀释度之间的一致性为99.8%。
本研究为在资源有限环境中确认HIV诊断的一种新的低成本方法提供了概念验证。它有潜力在确认算法中用作补充试验，即RDT双阳性结果进行稀释试验，阳性结果确认HIV感染。阴性结果需要进行核酸检测以排除由于血清转化或较低灵敏度稀释试验的错误分类导致的假阴性结果。需要进一步研究以确定这些结果是否能在其他环境中重现。
ClinicalTrials.gov，NCT01716299 。
