[HTML][HTML] A targeted reactivation of latent HIV-1 using an activator vector in patient samples from acute infection
EBioMedicine, 2020•thelancet.com
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 …
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 …
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
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