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The effect of panobinostat on HIV latency disruption in a phase 1/2 clinical trial

 

A new progress of HIV cure was reported on The Lancet HIV, recently. Rasmussen et al. found panobinostat, a histone deacetylase inhibitor, has the ability to activate infected cells from HIV latency. They also tested the safety of this strategy on phase 1/2 clinical trial.

 

Combination antiretroviral therapy is an efficient approach of HIV cure. However, the drugs need to act on different antiretroviral agents to suppress replication of HIV. Some HIV infected cells would not express viral proteins in the transcriptionally silent state, which is referred to as HIV latency. Therefore, combination antiretroviral therapy is ineffective on those resting cells.

 

It is reported that one of several approaches disrupt HIV latency in vitro is blocking histone deacetylation. Therefore, researchers tested the ability of the panobinostat, as a histone deacetylase inhibitor, to disrupt HIV latency in the phase 1/2 clinical trial. 15 aviraemic adults with HIV received oral panobinostat in a defined amount while maintaining combination antiretroviral therapy. An up-regulation of cell-associated unspliced HIV RNA was recorded during panobinostat treatment, indicating an disruption of HIV latency. Researchers recorded a transient decrease of total HIV DNA, but no significant change in total HIV DNA, integrated HIV DNA, or infectious units per million from baseline.

 

The effect of panobinostat treatment was not significant in reducing the number of latently infected cells. However, panobinostat effectively disrupt HIV latency in vivo and may contribute to HIV eradication in combination with other approaches in the future.

 

Reference:
The Lancet HIV. 2014 Oct;1(1):13-21.

 

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S1030 Panobinostat (LBH589) Panobinostat (LBH589, NVP-LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Panobinostat (LBH589) induces autophagy and apoptosis. Panobinostat effectively disrupts HIV latency in vivo. Phase 3.

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