HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy

Guinevere Q. Lee (), Pragya Khadka, Sarah N. Gowanlock, Dennis C. Copertino, Maggie C. Duncan, F. Harrison Omondi, Natalie N. Kinloch, Jingo Kasule, Taddeo Kityamuweesi, Paul Buule, Samiri Jamiru, Stephen Tomusange, Aggrey Anok, Zhengming Chen, R. Brad Jones, Ronald M. Galiwango, Steven J. Reynolds, Thomas C. Quinn, Zabrina L. Brumme, Andrew D. Redd and Jessica L. Prodger
Additional contact information
Guinevere Q. Lee: Weill Cornell Medicine
Pragya Khadka: Weill Cornell Medicine
Sarah N. Gowanlock: Western University
Dennis C. Copertino: Weill Cornell Medicine
Maggie C. Duncan: Simon Fraser University
F. Harrison Omondi: Simon Fraser University
Natalie N. Kinloch: Simon Fraser University
Jingo Kasule: Rakai Health Sciences Program
Taddeo Kityamuweesi: Rakai Health Sciences Program
Paul Buule: Rakai Health Sciences Program
Samiri Jamiru: Rakai Health Sciences Program
Stephen Tomusange: Rakai Health Sciences Program
Aggrey Anok: Rakai Health Sciences Program
Zhengming Chen: Weill Cornell Medicine
R. Brad Jones: Weill Cornell Medicine
Ronald M. Galiwango: Rakai Health Sciences Program
Steven J. Reynolds: Rakai Health Sciences Program
Thomas C. Quinn: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Zabrina L. Brumme: Simon Fraser University
Andrew D. Redd: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Jessica L. Prodger: Western University

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: Abstract The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-48985-9 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:15:y:2024:i:1:d:10.1038_s41467-024-48985-9

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

DOI: 10.1038/s41467-024-48985-9

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 ().