1. Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection
- Author
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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, and Eric J. Arts
- Subjects
HIV-1 latency reversal ,latency reversal agent ,virus-like particles ,CD4+ T cells ,chronic HIV-1 infection ,replication-competent latent reservoir ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - 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.
- Published
- 2024
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