RT Journal Article
SR Electronic
T1 HIV Diversity Considerations in the Application of the Intact Proviral DNA Assay (IPDA)
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.26.115006
DO 10.1101/2020.05.26.115006
A1 Natalie N. Kinloch
A1 Yanqin Ren
A1 Winiffer D. Conce Alberto
A1 Winnie Dong
A1 Pragya Khadka
A1 Szu Han Huang
A1 Talia M. Mota
A1 Andrew Wilson
A1 Aniqa Shahid
A1 Don Kirkby
A1 Marianne Harris
A1 Colin Kovacs
A1 Erika Benko
A1 Mario A. Ostrowski
A1 Perla M. Del Rio Estrada
A1 Avery Wimpelberg
A1 Christopher Cannon
A1 W. David Hardy
A1 Lynsay MacLaren
A1 Harris Goldstein
A1 Chanson J. Brumme
A1 Guinevere Q. Lee
A1 Rebecca M. Lynch
A1 Zabrina L. Brumme
A1 R. Brad Jones
YR 2020
UL http://biorxiv.org/content/early/2020/05/29/2020.05.26.115006.abstract
AB The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a precise and scalable method for intact HIV reservoir quantification1. This duplexed droplet digital PCR (ddPCR) assay simultaneously targets the HIV Packaging Signal (Ψ) and the Rev Responsive Element (RRE) within Envelope (env) to distinguish genomically intact proviruses against a large background of defective ones2. The IPDA requires less time, resources, and biological material than the gold standard for replication-competent HIV reservoir measurement, the Quantitative Viral Outgrowth Assay (QVOA)3, and is being adopted in research and clinical studies4–7. In our cohort of HIV-1 subtype B-infected individuals from North America however, the IPDA yielded a 28% failure rate due to HIV polymorphism. We further demonstrate that within-host HIV diversity can lead the IPDA to underestimate intact HIV reservoir size, which could negatively impact clinical trial results interpretation. While the IPDA represents an important methodological advance, HIV diversity should be addressed before its widespread adoption.Competing Interest StatementDr. R. Brad Jones declares that he has received payment for his previous role on the scientific advisory board of AbbVie Inc. Dr. Lynsay MacLaren declares that she holds the unpaid position of Advanced Practice Practitioner on the HIVMA Board of Directions. Dr. Marrianne Harris received honoraria paid to her institution for services as a consultant, membership on scientific advisory board and/or speaking engagement from Gilead Sciences Canada, Inc., Merck Canada Inc. and ViiV Healthcare