Work

Intact proviral DNA assay analysis of large cohorts of people with HIV provides a benchmark for the frequency and composition of persistent proviral DNA

Year: 2020

Type: article

Study design: Observational Study

Abstract: Significance Despite clinically effective antiretroviral therapy (ART), replication-competent HIV-1 persists as latent proviral DNA capable of rekindling viral replication when ART is stopped. To cure the infection, therapies are being developed to eliminate latent HIV-1. Accurate assays for intact or rebound-competent HIV-1 are important to this effort. We previously developed the intact proviral DNA assay (IPDA) as a more accurate and scalable assay for intact HIV-1 proviruses. Here we present IPDA analysis in a diverse cohort of 400 ART-treated individuals. We confirm that intact proviruses, although vastly outnumbered by defective proviruses, are present at significantly higher frequencies than previously detected by viral outgrowth assays. We also show that IPDA amplicon signal issues, observed in 6.3% of samples, result from sequence polymorphisms.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2006816117

Authors: Francesco R. Simonetti, Jennifer A. White, Camille Tumiotto, Kristen D. Ritter, Mian Cai, Rajesh T. Gandhi, Steven G. Deeks, Bonnie J. Howell, Luis J. Montaner, Joel N. Blankson, Albine Martin, Gregory M. Laird, Robert F. Siliciano, John W. Mellors, Janet D. Siliciano

Institutions: Johns Hopkins University, Johns Hopkins Medicine, University of Pittsburgh, Massachusetts General Hospital, University of California, San Francisco, Merck & Co., Inc., Rahway, NJ, USA (United States), The Wistar Institute, Howard Hughes Medical Institute

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Howard Hughes Medical Institute, National Institutes of Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, Office of Extramural Research, National Institutes of Health

Awards: G1162399445, G1386795942, G1826974679, BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy, G3936548522, G4553935269, Combined Immunologic Approaches to Cure HIV-1, Centralized Resource to Accurately Quantify Latent and Expressed HIV Reservoirs, Host and viral genomic determinants of HIV latent reservoir size and characteristics in individuals with substance use disorders, G857487509, Development of a quantitative assay for intact HIV DNA measures in tissue, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, The Johns Hopkins Center for AIDS Research (JHU CFAR), AIDS Clinical Trial Group Laboratory Center, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), G96469372, G97119092

OpenAlex ID: W3044571635

FWCI: 7.138

Cites: 41

Cited by: 113

Related to: 10