HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA)

Natalie N. Kinloch, Yanqin Ren, Winiffer D. Conce Alberto, Winnie Dong, Pragya Khadka, Szu Han Huang, Talia M. Mota, Andrew Wilson, Aniqa Shahid, Don Kirkby, Marianne Harris, Colin Kovacs, Erika Benko, Mario A. Ostrowski, Perla M. Rio Estrada, Avery Wimpelberg, Christopher Cannon, W. David Hardy, Lynsay MacLaren, Harris Goldstein, Chanson J. Brumme, Guinevere Q. Lee, Rebecca M. Lynch, Zabrina L. Brumme () and R. Brad Jones ()
Additional contact information
Natalie N. Kinloch: Simon Fraser University
Yanqin Ren: Weill Cornell Medical College
Winiffer D. Conce Alberto: Weill Cornell Medical College
Winnie Dong: British Columbia Centre for Excellence in HIV/AIDS
Pragya Khadka: Weill Cornell Medical College
Szu Han Huang: Weill Cornell Medical College
Talia M. Mota: Weill Cornell Medical College
Andrew Wilson: George Washington University
Aniqa Shahid: Simon Fraser University
Don Kirkby: British Columbia Centre for Excellence in HIV/AIDS
Marianne Harris: British Columbia Centre for Excellence in HIV/AIDS
Colin Kovacs: Maple Leaf Medical Clinic
Erika Benko: Maple Leaf Medical Clinic
Mario A. Ostrowski: University of Toronto
Perla M. Rio Estrada: National Institute of Respiratory Diseases
Avery Wimpelberg: Whitman Walker Health
Christopher Cannon: Whitman Walker Health
W. David Hardy: Whitman Walker Health
Lynsay MacLaren: Whitman Walker Health
Harris Goldstein: Albert Einstein College of Medicine
Chanson J. Brumme: British Columbia Centre for Excellence in HIV/AIDS
Guinevere Q. Lee: Weill Cornell Medical College
Rebecca M. Lynch: George Washington University
Zabrina L. Brumme: Simon Fraser University
R. Brad Jones: Weill Cornell Medical College

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-20442-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20442-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-20442-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().