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- Title
HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA).
- Authors
Kinloch, Natalie N.; Ren, Yanqin; Conce Alberto, Winiffer D.; Dong, Winnie; Khadka, Pragya; Huang, Szu Han; Mota, Talia M.; Wilson, Andrew; Shahid, Aniqa; Kirkby, Don; Harris, Marianne; Kovacs, Colin; Benko, Erika; Ostrowski, Mario A.; Del Rio Estrada, Perla M.; Wimpelberg, Avery; Cannon, Christopher; Hardy, W. David; MacLaren, Lynsay; Goldstein, Harris
- Abstract
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.
- Subjects
DNA; CELL-free DNA; BASIC needs; RESERVOIRS; CLINICAL trials
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-20442-3