Abstract

To date, an affordable, effective treatment for an HIV-1 cure remains only a concept with most “latency reversal” agents (LRAs) lacking specificity for the latent HIV-1 reservoir and failing in early clinical trials. We assessed HIV-1 latency reversal using a multivalent HIV-1-derived virus-like particle (HLP) to treat samples from 32 people living with HIV-1 (PLWH) in Uganda, US and Canada who initiated combined antiretroviral therapy (cART) during chronic infection. Even after 5–20 years on stable cART, HLP could target CD4+ T cells harbouring latent HIV-1 reservoir resulting in 100-fold more HIV-1 release into culture supernatant than by common recall antigens, and 1000-fold more than by chemotherapeutic LRAs. HLP induced release of a divergent and replication-competent HIV-1 population from PLWH on cART. These findings suggest HLP provides a targeted approach to reactivate the majority of latent HIV-1 proviruses among individuals infected with HIV-1.

Details

Title
Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection
Author
Minh Ha Ngo 1 ; Pankrac, Joshua 2 ; Ho, Ryan C Y 2 ; Ndashimye, Emmanuel 2 ; Pawa, Rahul 2 ; Ceccacci, Renata 2 ; Biru, Tsigereda 3 ; Olabode, Abayomi S 2 ; Klein, Katja 4 ; Li, Yue 2 ; Kovacs, Colin 5 ; Assad, Robert 6 ; Jacobson, Jeffrey M 6 ; Canaday, David H 6 ; Tomusange, Stephen 7 ; Samiri Jamiru 7 ; Aggrey Anok 7 ; Taddeo Kityamuweesi 7 ; Buule, Paul 7 ; Galiwango, Ronald M 7 ; Reynolds, Steven J 8 ; Quinn, Thomas C 9 ; Redd, Andrew D 9 ; Prodger, Jessica L 2 ; Mann, Jamie F S 4 ; Arts, Eric J 2 

 Department of Microbiology and Immunology, University of Western Ontario, London, Canada; College of Veterinary Medicine, Vietnam National University of Agriculture, Hanoi, Vietnam 
 Department of Microbiology and Immunology, University of Western Ontario, London, Canada 
 Department of Microbiology and Immunology, University of Western Ontario, London, Canada; Special Immunology Unit and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA 
 Department of Microbiology and Immunology, University of Western Ontario, London, Canada; Bristol Veterinary School, University of Bristol, Bristol, UK 
 Maple Leaf Medical Clinic and Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada 
 Special Immunology Unit and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA 
 Rakai Health Sciences Program, Kalisizo, Uganda 
 Rakai Health Sciences Program, Kalisizo, Uganda; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA 
 Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA 
Publication year
2024
Publication date
Dec 2024
Publisher
Taylor & Francis Ltd.
e-ISSN
22221751
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3142112124
Copyright
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. This work is licensed under the Creative Commons  Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.