Shanks Leslie, Siddiqui M Ruby, Kliescikova Jarmila, Pearce Neil, Ariti Cono, Muluneh Libsework, Pirou Erwan, Ritmeijer Koert, Masiga Johnson, Abebe Almaz
Médecins Sans Frontières, Amsterdam, The Netherlands.
Médecins Sans Frontières, London, UK.
BMC Infect Dis. 2015 Feb 3;15:39. doi: 10.1186/s12879-015-0769-3.
In Ethiopia a tiebreaker algorithm using 3 rapid diagnostic tests (RDTs) in series is used to diagnose HIV. Discordant results between the first 2 RDTs are resolved by a third 'tiebreaker' RDT. Médecins Sans Frontières uses an alternate serial algorithm of 2 RDTs followed by a confirmation test for all double positive RDT results. The primary objective was to compare the performance of the tiebreaker algorithm with a serial algorithm, and to evaluate the addition of a confirmation test to both algorithms. A secondary objective looked at the positive predictive value (PPV) of weakly reactive test lines.
The study was conducted in two HIV testing sites in Ethiopia. Study participants were recruited sequentially until 200 positive samples were reached. Each sample was re-tested in the laboratory on the 3 RDTs and on a simple to use confirmation test, the Orgenics Immunocomb Combfirm® (OIC). The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing.
2620 subjects were included with a HIV prevalence of 7.7%. Each of the 3 RDTs had an individual specificity of at least 99%. The serial algorithm with 2 RDTs had a single false positive result (1 out of 204) to give a PPV of 99.5% (95% CI 97.3%-100%). The tiebreaker algorithm resulted in 16 false positive results (PPV 92.7%, 95% CI: 88.4%-95.8%). Adding the OIC confirmation test to either algorithm eliminated the false positives. All the false positives had at least one weakly reactive test line in the algorithm. The PPV of weakly reacting RDTs was significantly lower than those with strongly positive test lines.
The risk of false positive HIV diagnosis in a tiebreaker algorithm is significant. We recommend abandoning the tie-breaker algorithm in favour of WHO recommended serial or parallel algorithms, interpreting weakly reactive test lines as indeterminate results requiring further testing except in the setting of blood transfusion, and most importantly, adding a confirmation test to the RDT algorithm. It is now time to focus research efforts on how best to translate this knowledge into practice at the field level.
Clinical Trial registration #: NCT01716299.
在埃塞俄比亚，采用串联使用3种快速诊断检测（RDT）的决胜算法来诊断HIV。前两种RDT之间不一致的结果通过第三种“决胜”RDT来解决。无国界医生组织采用另一种串联算法，即先进行2种RDT检测，然后对所有双阳性RDT结果进行确认检测。主要目的是比较决胜算法与串联算法的性能，并评估在两种算法中添加确认检测的情况。次要目的是观察弱阳性检测线的阳性预测值（PPV）。
该研究在埃塞俄比亚的两个HIV检测点进行。依次招募研究参与者，直至获得200份阳性样本。每个样本在实验室中用3种RDT以及一种易于使用的确认检测——奥根尼克斯免疫组合确认检测（Orgenics Immunocomb Combfirm®，OIC）重新检测。金标准检测是免疫印迹法，不确定的结果通过PCR检测来解决。
纳入2620名受试者，HIV患病率为7.7%。3种RDT中的每一种的个体特异性至少为99%。采用2种RDT的串联算法有1例假阳性结果（204例中的1例），PPV为99.5%（95%CI：97.3%-100%）。决胜算法产生了16例假阳性结果（PPV为92.7%，95%CI：88.4%-95.8%）。在任何一种算法中添加OIC确认检测都消除了假阳性。所有假阳性在算法中都至少有一条弱阳性检测线。弱阳性RDT的PPV显著低于强阳性检测线的PPV。
决胜算法中HIV诊断出现假阳性的风险很大。我们建议放弃决胜算法，转而采用世界卫生组织推荐的串联或并联算法，将弱阳性检测线解释为不确定结果，需要进一步检测，但输血情况除外，最重要的是，在RDT算法中添加确认检测。现在是时候将研究重点放在如何最好地将这一知识转化为现场实际应用了。
临床试验注册号：NCT01716299。
