20th International AIDS Conference - Melbourne, Australia


MOSY05 Viral Latency and Reservoirs: The Keys to Cure
  Symposia Session
Venue: Plenary 1
Time: 21.07.2014, 14:30 - 16:00
Co-Chairs: Asier Sáez-Cirión, France
Jeffrey Lifson, United States

This session is directed to scientists and clinicians interested in learning about the mechanisms ensuring HIV latency and persistence of the HIV reservoirs and understanding their importance in the design of therapeutic strategies aiming at inducing a functional cure for HIV. The session will address the critical mechanisms that explain how the virus integrates with the human genome. The presentations will review how HIV persistence is established, in particular how it is controlled by restriction factors or dependent on T cell homeostasis and how it hides into tissular sanctuaries. At the completion of the session, participants will understand the recent advances on viral latency and reservoirs and how they can be translated into progress towards effective eradication strategies.
14:30
MOSY0501
The path towards HIV cure: Lessons from the MISSISSIPPI CHILD
D. Persaud, United States

14:40
MOSY0502
What is latency and what are its determinates?
C. Van Lint, Belgium

14:50
MOSY0503
Powerpoint
Webcast
Restriction factors of HIV in myeloid and T cells
E. Verdin, United States

15:10
MOSY0504
Impact of T cell homeostasis on HIV reservoirs
N. Chomont, United States

15:25
MOSY0505
Powerpoint
Webcast
Tissue reservoirs
M. Churchill, Australia

15:35
MOSY0506
Webcast
Questions and answers

15:55
MOSY0507
Webcast
Closing remarks

Powerpoints presentations
Restriction factors of HIV in myeloid and T cells - Eric Verdin

Tissue reservoirs - Melissa Churchill



Rapporteur report

Track A report by Renee van der Sluis


This symposium provided a comprehensive overview of HIV-1 latency and reservoirs, including the latest information on the ‘Mississippi child’, molecular mechanisms contributing to latency, current approaches to target the reservoir, the complexity of T cell subsets and the contribution of tissues, notably the CNS, as a reservoir.

 

Dr. Persaud (USA) offered a late-breaker update on the ‘Mississippi Child’ who recently experienced HIV rebound after 27 months of viral remission in the absence of therapy. Despite this setback, Dr. Persaud was optimistic about the length of remission observed and she underscored the importance of early therapy initiation, emphasizing this case as strong in vivo evidence supporting early establishment of the latent reservoir following infection.

 

Dr. van Lint (Belgium) followed with a detailed description of the multifactorial molecular, epigenetic and non-epigenetic mechanisms associated with viral latency. She discussed clinical trials using HDAC inhibitors to reactivate latent HIV according to the ‘shock and kill’ approach whilst patients remain on cART. This strategy aims to reactivate HIV (shock) to produce viral proteins and/or virus particles that will subsequently lead to the elimination of infected cells due to virus-induced cytopathic effects or recognition of the infected cell by the immune system (kill). These trials have indicated that the HDAC inhibitors will likely need to be combined with other agents, such as vaccines, to effectively eliminate latent HIV. 

 

Dr. Verdin (USA) presented a study in which an shRNA library targeting nearly 19,000 cellular proteins was used to identify host proteins that contribute to reactivation of latent virus. This work revealed several novel protein complexes that may regulate HIV latency, including mTOR and TGF-beta. Notably, inhibitors of the mTOR pathway blocked reactivation viral latency, providing a potential alternative to ‘shock and ‘kill’ where virus might be permanently silenced.

 

The last two speakers illustrated the complexity of the latent reservoir and also highlighted the fact that multiple cell types and cell subsets contribute to the latent pool.  Dr. Chomont (USA) provided an overview of T cell subsets, demonstrating that they showed remarkable differences in terms of their contribution to the reservoir as well as their susceptibility to reactivation. He also presented data suggesting that early initiation of cART did not prevent latency establishment, however the size of the reservoir in each T cell subset was reduced.

 

Finally, Dr. Churchill (Australia) gave an excellent summary of the current knowledge on the CNS as an HIV sanctuary, emphasizing that various anatomical sites display different features compared to peripheral blood in terms of drug penetration and that neuronal cells permissive for viral replication and latency, such as astrocytes, will require different approaches since it would be unfavourable to induce cell death in the CNS network.

 

Altogether, this session provided an excellent opportunity for participants to improve and update their understanding of HIV latency.  Speakers presented the many remaining challenges to target latent HIV-1, but also demonstrated what we already know a lot about the diversity of latent cells and complexity of reservoirs. Take home messages: early start of ARV reduces the size of the reservoir and we will likely need several approaches to target all viral sanctuary sites due to its multifaceted nature.




   

    The organizers reserve the right to amend the programme.