Miranda Smith
Key lessons from Keystone
Keystone symposia bring together focused groups of scientists to discuss unpublished research. They provide insights into the current thinking around scientific topics. This year’s Keystone symposium ‘Functional Cures and the Eradication of HIV’ took place in late March. We spoke to Kirby Institute researcher, Chantelle Ahlenstiel to find out what caught her attention.
Can latent HIV be re-activated?
The presentation from San Francisco researcher Eric Verdin triggered a lot of discussion. He explored the differences between latent cells that are and are not responsive to latency reversing agents. His group looked at where HIV inserts itself into host DNA (integration sites), and the DNA structures (chromatin modifications) surrounding the inserted HIV. Both these factors influence whether the inserted HIV can replicate again after a period of latency. Verdin’s results demonstrated that most cells with latent HIV can’t be reactivated. This doesn’t bode well for the use of latency-reversal approaches alone as an HIV cure strategy.
Advances in permanent HIV silencing
A few presenters focused on the ‘block and lock’ approach to HIV cure. ‘Block and lock’ is a strategy to push HIV into ‘deep latency’ where it cannot be re-activated. There have already been some proof-of-concept studies in cell lines and mouse models. Didehydro-Corticostatin A (dCA) is one compound that has been studied.
Dr Susana Valente from the Scripps Research Institute in Florida presented further work on dCA. She described in more detail how it works, and provided further evidence for its use in blocking HIV. Dr Ahlenstiel herself presented evidence on using the PromA molecule to silence HIV in mouse models of both acute and chronic HIV. Fabio Romerio from the University of Maryland presented data on a small by-product of HIV infection called the antisense transcript (Ast). He described how Ast encourages HIV latency through changing the DNA structures around the virus (epigenetic changes).
Other approaches to HIV cure
Despite the big question about whether latent HIV can be reactivated, new latency reversing agents (LRAs) featured strongly. These included combination approaches with LRAs; vaccines; neutralising antibodies and additional immune-modulating agents such as GS-9620 which we’ve written about previously.
Other presentations addressed gene editing approaches. These included the use of CRISPR/Cas9 and Chimeric Antigen Receptor (CAR) T cells. Scott Kitchen from the University of California, Los Angeles, gave an engaging talk on the development of CAR-T cells targeting HIV-infected cells, which are now progressing towards human clinical trials.
Reflecting on the conference, Dr Ahlenstiel says
There is a huge breadth of work going on around the world to find ways to cure HIV. It won’t be easy, and the take-home message for me is that there is unlikely to ever be a one-size-fits-all solution. Similar to combined ART, an HIV cure is likely to be a combination of cure approaches.
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