HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA).
HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA).
复制标题
DOI：
10.1038/s41467-020-20442-3
复制
发表时间：
2021-01-08
影响因子：
16.6
通讯作者：
Jones RB
中科院分区：
文献类型：
--
作者：
Kinloch NN;Ren Y;Conce Alberto WD;Dong W;Khadka P;Huang SH;Mota TM;Wilson A;Shahid A;Kirkby D;Harris M;Kovacs C;Benko E;Ostrowski MA;Del Rio Estrada PM;Wimpelberg A;Cannon C;Hardy WD;MacLaren L;Goldstein H;Brumme CJ;Lee GQ;Lynch RM;Brumme ZL;Jones RB
开发完整前病毒DNA检测试剂盒（IPDA）是为了满足对完整HIV-1储库定量的可扩展方法的迫切需求。这种基于液滴数字PCR的检测方法同时靶向两个HIV-1区域，以区分基因组完整的前病毒和大量有缺陷的前病毒，其应用已经深入了解了HIV-1的持久性。然而，最近出现了归因于HIV-1多态性的检测失败的报告。在这里，我们描述了一个不同的北美人群与HIV-1亚型B，其中IPDA产生了28%的失败率，由于病毒的多态性。我们进一步证明，宿主内HIV-1的多样性可能导致IPDA低估完整的水库大小，并提供了这种现象如何导致临床试验数据的错误解释的例子。虽然IPDA代表了一个重大的方法学进步，但在将其作为HIV-1缓解试验的主要读数广泛采用之前，应解决HIV-1多样性问题。完整前病毒DNA检测可定量基因组完整的HIV储库，但已观察到因HIV-1多态性导致的检测失败。在这里，作者报告了一组HIV-1感染者的失败率为28%，并指出宿主内HIV-1的多样性是对IPDA准确性的进一步挑战。
The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a scalable method for intact HIV-1 reservoir quantification. This droplet digital PCR-based assay simultaneously targets two HIV-1 regions to distinguish genomically intact proviruses against a large background of defective ones, and its application has yielded insights into HIV-1 persistence. Reports of assay failures however, attributed to HIV-1 polymorphism, have recently emerged. Here, we describe a diverse North American cohort of people with HIV-1 subtype B, where the IPDA yielded a failure rate of 28% due to viral polymorphism. We further demonstrate that within-host HIV-1 diversity can lead the IPDA to underestimate intact reservoir size, and provide examples of how this phenomenon could lead to erroneous interpretation of clinical trial data. While the IPDA represents a major methodological advance, HIV-1 diversity should be addressed before its widespread adoption as a principal readout in HIV-1 remission trials. The intact proviral DNA assay quantifies the genomically intact HIV reservoir, but assay failure due to HIV-1 polymorphism has been observed. Here, the authors report a 28% failure rate in a cohort of people with HIV-1, and note within-host HIV-1 diversity as a further challenge to IPDA accuracy.
登录
查看更多内容
影响因子：
16.6
作者：
Bruel T;Guivel-Benhassine F;Amraoui S;Malbec M;Richard L;Bourdic K;Donahue DA;Lorin V;Casartelli N;Noël N;Lambotte O;Mouquet H;Schwartz O
通讯作者：
Schwartz O
DOI：
10.1093/cid/ciaa809
发表时间：
2020-06-18
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Papasavvas, Emmanouil;Azzoni, Livio;Montaner, Luis J
通讯作者：
Montaner, Luis J
影响因子：
15.3
作者：
Gaebler, Christian;Lorenzi, Julio C. C.;Nussenzweig, Michel C.
通讯作者：
Nussenzweig, Michel C.
影响因子：
15.9
作者：
Lee, Guinevere Q.;Orlova-Fink, Nina;Lichterfeld, Mathias
通讯作者：
Lichterfeld, Mathias
影响因子：
64.5
作者：
Ho YC;Shan L;Hosmane NN;Wang J;Laskey SB;Rosenbloom DI;Lai J;Blankson JN;Siliciano JD;Siliciano RF
通讯作者：
Siliciano RF