In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. We evaluated the performance of the antibody and antigen components of the old and novel version of the Determine™ HIV-1/2 Ag/Ab Combo RDTs in parallel to quantifications in a fourth-generation antigen/antibody immunoassay (4G-EIA), p24CA antigen immunoassay (p24CA-EIA), immunoblots, and nucleic acid quantification. We included plasma samples of acute, treatment-naïve HIV-1 infections (Fiebig stages I–VI, subtypes A1, B, C, F, CRF02_AG, CRF02_AE, URF) or chronic HIV-1 and HIV-2 infections. The tests’ antigen component was evaluated also for a panel of subtype B HIV-1 transmitted/founder (T/F) viruses, HIV-2 strains and HIV-2 primary isolates. Furthermore, we assessed the analytical sensitivity of the RDTs to detect p24CA using a highly purified HIV-1_NL4-3 p24CA standard. We found that 77% of plasma samples from acutely infected, immunoblot-negative HIV-1 patients in Fiebig stages II–III were identified by the new RDT, while only 25% scored positive in the old RDT. Both RDTs reacted to all samples from chronically HIV-1-infected and acutely HIV-1-infected patients with positive immunoblots. All specimens from chronically infected HIV-2 patients scored positive in the new RDT. Of note, the sensitivity of the RDTs to detect recombinant p24CA from a subtype B virus ranged between 50 and 200 pg/mL, mirrored also by the detection of HIV-1 T/F viruses only at antigen concentrations tenfold higher than suggested by the manufacturer. The RTD failed to recognize any of the HIV-2 viruses tested. Our results indicate that the new version of the Determine™ HIV-1/2 Ag/Ab Combo displays an increased sensitivity to detect HIV-1 p24CA-positive, immunoblot-negative plasma samples compared to the precursor version. The sensitivity of 4G-EIA and p24CA-EIA to detect the major structural HIV antigen, and thus to diagnose acute infections prior to seroconversion, is still superior.

中文翻译：

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在急性和慢性HIV感染中，对Define™HIV-1 / 2 Ag / Ab Combo快速诊断测试进行比较性多重测定评估。

在资源有限或现场护理点设置中，旨在以高灵敏度同时检测HIV抗体和p24衣壳（p24CA）抗原的快速诊断测试（RDT）可以成为筛选早期感染的重要替代方法。我们在第四代抗原/抗体免疫分析（4G-EIA），p24CA中定量分析的同时，评估了旧版和新型版的Define™HIV-1 / 2 Ag / Ab Combo RDT的抗体和抗原成分的性能抗原免疫测定（p24CA-EIA），免疫印迹和核酸定量。我们包括了急性，未经治疗的HIV-1感染（费伯格I至VI期，亚型A1，B，C，F，CRF02_AG，CRF02_AE，URF）或慢性HIV-1和HIV-2感染的血浆样本。还针对一组B型HIV-1传播/建立者（T / F）病毒对测试的抗原成分进行了评估，HIV-2株和HIV-2主要分离株。此外，我们评估了RDT对高纯度HIV-1检测p24CA的分析敏感性_NL4-3p24CA标准。我们发现，在Fiebig II至III期急性感染，免疫印迹阴性的HIV-1患者中，有77％的血浆样品被新的RDT鉴定，而只有25％的旧RDT呈阳性。两种RDT对来自阳性HIV-1感染的慢性HIV-1和急性HIV-1感染患者的所有样品都有反应。来自慢性感染HIV-2患者的所有标本在新的RDT中得分均为阳性。值得注意的是，RDT对B型亚型病毒检测重组p24CA的敏感性介于50 pg / mL至200 pg / mL之间，这也反映在仅以比制造商建议高十倍的抗原浓度检测HIV-1 T / F病毒的情况下。RTD无法识别测试的任何HIV-2病毒。我们的结果表明，与前一版本相比，新版本的Define™HIV-1 / 2 Ag / Ab Combo显示出更高的检测HIV-1 p24CA阳性，免疫印迹阴性血浆样品的灵敏度。4G-EIA和p24CA-EIA检测主要结构HIV抗原，从而在血清转化之前诊断急性感染的敏感性仍然更高。