Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection

Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection

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 par...

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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Emerging Microbes and Infections
Subjects:
HIV-1 latency reversal
latency reversal agent
virus-like particles
CD4+ T cells
chronic HIV-1 infection
replication-competent latent reservoir
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2024.2327371
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Summary: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.
ISSN:2222-1751

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