Emerging Microbes and Infections (Dec 2024)
Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection
- Minh Ha Ngo,
- Joshua Pankrac,
- Ryan C. Y. Ho,
- Emmanuel Ndashimye,
- Rahul Pawa,
- Renata Ceccacci,
- Tsigereda Biru,
- Abayomi S. Olabode,
- Katja Klein,
- Yue Li,
- Colin Kovacs,
- Robert Assad,
- Jeffrey M. Jacobson,
- David H. Canaday,
- Stephen Tomusange,
- Samiri Jamiru,
- Aggrey Anok,
- Taddeo Kityamuweesi,
- Paul Buule,
- Ronald M. Galiwango,
- Steven J. Reynolds,
- Thomas C. Quinn,
- Andrew D. Redd,
- Jessica L. Prodger,
- Jamie F. S. Mann,
- Eric J. Arts
Affiliations
- Minh Ha Ngo
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Joshua Pankrac
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Ryan C. Y. Ho
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Emmanuel Ndashimye
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Rahul Pawa
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Renata Ceccacci
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Tsigereda Biru
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Abayomi S. Olabode
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Katja Klein
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Yue Li
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Colin Kovacs
- Maple Leaf Medical Clinic and Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada
- Robert Assad
- Special Immunology Unit and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
- Jeffrey M. Jacobson
- Special Immunology Unit and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
- David H. Canaday
- Special Immunology Unit and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
- Stephen Tomusange
- Rakai Health Sciences Program, Kalisizo, Uganda
- Samiri Jamiru
- Rakai Health Sciences Program, Kalisizo, Uganda
- Aggrey Anok
- Rakai Health Sciences Program, Kalisizo, Uganda
- Taddeo Kityamuweesi
- Rakai Health Sciences Program, Kalisizo, Uganda
- Paul Buule
- Rakai Health Sciences Program, Kalisizo, Uganda
- Ronald M. Galiwango
- Rakai Health Sciences Program, Kalisizo, Uganda
- Steven J. Reynolds
- Rakai Health Sciences Program, Kalisizo, Uganda
- Thomas C. Quinn
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Andrew D. Redd
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Jessica L. Prodger
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Jamie F. S. Mann
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- Eric J. Arts
- Department of Microbiology and Immunology, University of Western Ontario, London, Canada
- DOI
- https://doi.org/10.1080/22221751.2024.2327371
- Journal volume & issue
-
Vol. 13,
no. 1
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.
Keywords
- HIV-1 latency reversal
- latency reversal agent
- virus-like particles
- CD4+ T cells
- chronic HIV-1 infection
- replication-competent latent reservoir
