News From HIV Persistence Workshop Day 2 PDF Print E-mail
Written by Alain Lafeuillade   
Wednesday, 07 December 2011 00:00

HIV Persistence, Reservoirs and Eradication Strategies Workshop: Day 2

HIV_persistende_d2The second day of the workshop, on December 7, 2011, addressed the issues of "Models of HIV Persistence", "Basic Science of HIV Persistence" and "Virological Aspects of HIV Persistence". Although a scientific article will be published in the next few months as proceedings of this workshop, we are pleased to briefly share with you the main discussions that animated today's debates.

 

This morning session addressed different models of HIV infection including animal and cellular models. These presentation will be the subject of a specific report in a few weeks. The data presented by the team of Andrea Savarino are summarized in the following press release:


http://www.prweb.com/releases/2011/12/prweb8966154.htm

The afternoon session dealed with the virological aspects of HIV persistence.

Sarah Palmer characterized HIV reservoirs during effective therapy in 12 patients by analyzing cells from blood, bone marrow and gut. She compared phylogenetically the virus isolated from different cellular compartments. She used single-genome sequencing from plasma virus and from provirus from cell samples. In patients treated at the chronic phase (7) the reservoir in blood memory T cells was 13 fold higher than in patients (5) treated at acute infection. In bone marrow no single infected hematopoietic precursor cell was found. This infection of lymphoid CD4+ T cells was 21 fold higher in patients treated at chronic rather at acute infection. But genetic analysis showed that these cells were trafficking between bone marrow and blood.
In a patients treated at acute infection, viral sequences were almost identical in blood, gut and bone marrow after 12 years of ART. In another patient treated at acute infection for 8 years but who was initially infected with different viral variants, no indication of evolution was also found in blood, gut and bone marrow. Lastly, a patient treated at the chronic stage was also analyzed after 9 years of therapy, a mutant with a protease gene delection was found in blood and bone marrow.

Tae-Wook Chun then addressed the perspectives in HIV eradication. In vitro, Prostratin is as effective as anti-CD3 to activate HIV from resting CD4+ T cells from infected individuals on ART. SAHA was also effective but clearly less than Prostratin. One of the main question with HDAC inhibitors is whether cells in which HIV is activated will die. In vitro data tend to show that they do not. Tae-Wook emphasized the need for more sensitive virological assays to measure HIV persistence and the fact that it is probably not possible to get to a functional cure without having an increased immune control of the few remaining cells.

Javier Martinez-Picado argued for the existence of ongoing viral replication during effective ART. The IntegRal study was published by Buzon et al in 2010 and showed that cDNA intermediates and integrated DNA did not change. An accumulation of 2-LTR circles was found in 13 individuals. This study led to the deep molecular characterization of HIV dynamics under suppressive ART by comparing episomal versus integrated DNA. The results show that a compartment where ARVs are not psent at sufficient levels or are not metabolized correctly may persist. CD8 activation decreased during the 48 weeks of raltegravir intensification. When RAL was stopped, CD8 activation increased in the patients who showed a transient increase in 2-LTR circles only. 



Key words: HIV cure, HIV eradication, HIV persistence, HIV reservoirs
Last Updated on Thursday, 08 December 2011 02:31
 

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