A targeted reactivation of latent HIV-1 using an activator vector in patient samples from acute infection

EBioMedicine. 2020 Sep;59:102853. doi: 10.1016/j.ebiom.2020.102853. Epub 2020 Jul 9.


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-γ 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.

Funding: NIH and CIHR.

Keywords: Activator vector (ACT-VEC); HIV-1 Cure; HIV-1 Latency; Immunotherapy; Transcriptional reactivation; Virus-Like Particles.

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • Biomarkers
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • Female
  • Gene Expression Regulation, Viral / drug effects
  • Gene Order
  • Genetic Vectors* / genetics
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / physiology*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / virology
  • RNA, Viral
  • Viral Load
  • Virus Activation*
  • Virus Latency*
  • Virus Replication / genetics
  • Young Adult


  • Biomarkers
  • RNA, Viral