Impact of misclassified defective proviruses on HIV reservoir measurements

Daniel B. Reeves (), Christian Gaebler, Thiago Y. Oliveira, Michael J. Peluso, Joshua T. Schiffer, Lillian B. Cohn, Steven G. Deeks and Michel C. Nussenzweig
Additional contact information
Daniel B. Reeves: Fred Hutchinson Cancer Center
Christian Gaebler: The Rockefeller University
Thiago Y. Oliveira: The Rockefeller University
Michael J. Peluso: Infectious Diseases, and Global Medicine, Department of Medicine, UCSF
Joshua T. Schiffer: Fred Hutchinson Cancer Center
Lillian B. Cohn: Fred Hutchinson Cancer Center
Steven G. Deeks: Infectious Diseases, and Global Medicine, Department of Medicine, UCSF
Michel C. Nussenzweig: The Rockefeller University

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: Abstract Most proviruses persisting in people living with HIV (PWH) on antiretroviral therapy (ART) are defective. However, rarer intact proviruses almost always reinitiate viral rebound if ART stops. Therefore, assessing therapies to prevent viral rebound hinges on specifically quantifying intact proviruses. We evaluated the same samples from 10 male PWH on ART using the two-probe intact proviral DNA assay (IPDA) and near full length (nfl) Q4PCR. Both assays admitted similar ratios of intact to total HIV DNA, but IPDA found ~40-fold more intact proviruses. Neither assay suggested defective proviruses decay over 10 years. However, the mean intact half-lives were different: 108 months for IPDA and 65 months for Q4PCR. To reconcile this difference, we modeled additional longitudinal IPDA data and showed that decelerating intact decay could arise from very long-lived intact proviruses and/or misclassified defective proviruses: slowly decaying defective proviruses that are intact in IPDA probe locations (estimated up to 5%, in agreement with sequence library based predictions). The model also demonstrates how misclassification can lead to underestimated efficacy of therapies that exclusively reduce intact proviruses. We conclude that sensitive multi-probe assays combined with specific nfl-verified assays would be optimal to document absolute and changing levels of intact HIV proviruses.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39837-z 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:14:y:2023:i:1:d:10.1038_s41467-023-39837-z

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

DOI: 10.1038/s41467-023-39837-z

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 ().