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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.
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Details
1 Department of Microbiology and Immunology, University of Western Ontario, London, Canada; College of Veterinary Medicine, Vietnam National University of Agriculture, Hanoi, Vietnam
2 Department of Microbiology and Immunology, University of Western Ontario, London, Canada
3 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
4 Department of Microbiology and Immunology, University of Western Ontario, London, Canada; Bristol Veterinary School, University of Bristol, Bristol, UK
5 Maple Leaf Medical Clinic and Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada
6 Special Immunology Unit and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
7 Rakai Health Sciences Program, Kalisizo, Uganda
8 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
9 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