Journal
EBIOMEDICINE
Volume 59, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ebiom.2020.102853
Keywords
HIV-1 Latency; Virus-Like Particles; HIV-1 Cure; Transcriptional reactivation; Activator vector (ACT-VEC); Immunotherapy
Funding
- NIH [AI49170]
- amfAR ARCHE [108838-55-RGRL, 108686-54-RGRL]
- CIHR [PJT 149075, 377790, 385787]
- NIH AIDS Reagent Program, NIAID, NIH [MOLT-4/CCR5]
- MRC [MR/L00528X/1] Funding Source: UKRI
Ask authors/readers for more resources
Background: During combined anti-retroviral treatment, a latent HIV reservoir persists within resting memory CD4 T cells that initiates viral recrudescence upon treatment interruption. Strategies for HIV-1 cure have largely focused on latency reversing agents (LRAs) capable of reactivating and eliminating this viral reservoir. Previously investigated LRAs have largely failed to achieve a robust latency reversal sufficient for reduction of latent HIV pool or the potential of virus-free remission in the absence of treatment. Methods: We utilize a polyvalent virus-like particle (VLP) formulation called Activator Vector (ACT-VEC) to 'shock' provirus into transcriptional activity. Ex vivo co-culture experiments were used to evaluate the efficacy of ACT-VEC in relation to other LRAs in individuals diagnosed and treated during the acute stage of infection. IFN-gamma ELISpot, qRT-PCR and Illumina MiSeq were used to evaluate antigenicity, latency reversal, and diversity of induced virus respectively. Findings: Using samples from HIV+ patients diagnosed and treated at acute/early infection, we demonstrate that ACT-VEC can reverse latency in HIV infected CD4 T cells to a greater extent than other major recall antigens as stimuli or even mitogens such as PMA/Iono. Furthermore, ACT-VEC activates more latent HIV-1 than clinically tested HDAC inhibitors or protein kinase C agonists. Interpretation: Taken together, these results show that ACT-VEC can induce HIV reactivation from latently infected CD4 T cells collected from participants on first line combined antiretroviral therapy for at least two years after being diagnosed and treated at acute/early stage of infection. These findings could provide guidance to possible targeted cure strategies and treatments. (C) 2020 The Author(s). Published by Elsevier B.V.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available