Blood Systems Research Institute, San Francisco, California, USA
Department of Laboratory Medicine, University of California, San Francisco, California, USA.
J Clin Microbiol. 2018 Jul 26;56(8). doi: 10.1128/JCM.02045-17. Print 2018 Aug.
Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical fourth-generation antigen (Ag)/antibody (Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab-alone assays but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening, and next-generation assays. Three-hundred-member panels of 20 serially diluted well-characterized antibody-negative HIV isolates for which the researchers were blind to the results (blind panels) were distributed to manufacturers and end-user labs to assess the relative analytic sensitivity of currently approved and preapproved clinical HIV fourth-generation Ag/Ab combo or p24 Ag-alone immunoassays for the detection of diverse subtypes. The limits of detection (LODs) of virus were estimated for different subtypes relative to confirmed viral loads. Analysis of immunoassay sensitivity was benchmarked against confirmed viral load measurements on the blind panel. On the basis of the proportion of positive results on 300 observations, all Ag/Ab combo and standard sensitivity p24 Ag assays performed similarly and within half-log LODs, illustrating the similar breadth of reactivity and diagnostic utility. Ultrasensitive p24 Ag assays achieved dramatically increased sensitivities, while the rapid combo assays performed poorly. The similar performance of the different commercially available fourth-generation assays on diverse subtypes supports their use in broad geographic settings with locally circulating HIV clades and recombinant strains. Next-generation preclinical ultrasensitive p24 Ag assays achieved dramatically improved sensitivity, while rapid fourth-generation assays performed poorly for p24 Ag detection.
急性 HIV 感染的检测对于 HIV 公共卫生和诊断至关重要。与仅检测抗体的检测相比，临床第四代抗原（Ag）/抗体（Ab）组合（组合）和 p24Ag 免疫测定法增强了急性感染的检测，但需要用当前流行的不同亚型进行持续评估。使用遗传和地理上多样化的 HIV 临床分离株来评估临床 HIV 诊断、血液筛查和下一代检测。将 20 种具有代表性的、连续稀释的、特征明确的、抗体阴性的 HIV 临床分离株的 300 个成员小组（盲测小组）分发给制造商和最终用户实验室，以评估目前批准和预批准的临床第四代 Ag/Ab 组合或 p24Ag 单克隆抗体免疫测定法检测不同亚型的相对分析灵敏度。根据相对于确认病毒载量的病毒检测下限（LOD）来估计不同亚型的 LOD。对免疫测定法灵敏度的分析是基于盲测小组上的确认病毒载量测量来进行基准测试的。根据 300 次观察的阳性结果比例，所有 Ag/Ab 组合和标准灵敏度 p24Ag 检测均表现相似，且在半对数 LOD 范围内，表明反应性和诊断实用性相似。超灵敏 p24Ag 检测法的灵敏度显著提高，而快速组合检测法的性能不佳。不同商业上可用的第四代检测在不同亚型上的相似性能支持在具有当地流行的 HIV 分支和重组株的广泛地理环境中使用它们。下一代临床前超灵敏 p24Ag 检测法的灵敏度显著提高，而快速第四代 p24Ag 检测法的检测性能不佳。
