School of Pathology University of the Witwatersrand, Johannesburg, South Africa.
PLoS One. 2012;7(9):e42322. doi: 10.1371/journal.pone.0042322. Epub 2012 Sep 11.
We describe the application of a novel HIV confirmatory testing algorithm to determine the primary efficacy endpoint in a large Phase III microbicide trial. 9385 women were enrolled between 2005 and 2009. Of these women, 537 (6%) had at least one positive HIV rapid test after enrolment. This triggered the use of the algorithm which made use of archived serum and Buffy Coat samples. The overall sample set was >95% complete. 419 (78%) of the rapid test positive samples were confirmed as primary endpoints using a combination of assays for the detection of HIV-specific antibodies (EIA's and Western Blot), and for components of the virus itself (PCR for the detection of nucleic acids and EIA for p24 antigen). 63 (12%) cases were confirmed as being HIV-positive at screening or enrolment and 55 (10%) were confirmed as HIV negative. The testing algorithm confirmed the endpoint at the same visit as that of the first positive rapid test in 90% of cases and at the time of the preceding visit in 10% of cases. Of the 63 cases which were subsequently confirmed to be HIV-1 positive at or before enrolment, 54 specimens contained no detectable HIV antibodies at screening or enrolment. However, 43 were positive using an EIA which detects both HIV antigen and antibody and also had a positive p24 antigen or HIV PCR test, which was highly suggestive of acute infection. There were 6 unusual cases which had undetectable HIV-1 DNA or RNA. In 4 of the 6 cases the presence of HIV-1-specific antibodies was confirmed by Western Blot. One of these cases with an indeterminate Western Blot was a previous vaccine trial participant. The algorithm served the objectives of the study well and can be recommended for use in determining HIV as an endpoint in clinical trials.
ISRCTN.org ISRCTN 64716212.
我们描述了一种新的 HIV 确认检测算法在一项大型 III 期杀微生物剂试验中的应用，以确定主要疗效终点。2005 年至 2009 年间共招募了 9385 名女性。其中 537 名（6%）在入组后至少有一次 HIV 快速检测阳性。这触发了算法的使用，该算法利用了存档的血清和 Buffy Coat 样本。整个样本集的完成率超过 95%。使用一系列检测 HIV 特异性抗体（EIA 和 Western Blot）和病毒本身成分（检测核酸的 PCR 和 p24 抗原的 EIA）的组合，对 419 名（78%）快速检测阳性样本进行了确认作为主要终点。63 例（12%）在筛查或入组时被确认为 HIV 阳性，55 例（10%）被确认为 HIV 阴性。在 90%的病例中，该检测算法在第一次快速检测阳性的同一就诊时确认了终点，在 10%的病例中在之前就诊时确认了终点。在随后在入组前或入组时被确认为 HIV-1 阳性的 63 例病例中，54 例在筛查或入组时未检测到可检测的 HIV 抗体。然而，使用同时检测 HIV 抗原和抗体的 EIA，以及 HIV p24 抗原或 HIV PCR 检测呈阳性的 43 例，高度提示为急性感染。有 6 例异常病例的 HIV-1DNA 或 RNA 无法检测到。在 6 例中的 4 例中，Western Blot 证实存在 HIV-1 特异性抗体。其中一例 Western Blot 不确定的病例是以前的疫苗试验参与者。该算法很好地满足了研究的目标，可以推荐用于确定 HIV 作为临床试验的终点。
ISRCTN.org ISRCTN 64716212。
