6th IAS Conference On HIV Pathogenesis, Treatment and Prevention

Towards an HIV Cure: New Strategies for an Old Challenge WESY01

Type:
Symposium Back
Venue: SR 1
Time: 11:00 - 12:30, 20.07.2011
Code: WESY01
Chairs: Christine Rouzioux, France
Sharon Lewin, Australia

This session aims at presenting novel strategies being explored to address the challenge of HIV persistence under antiretroviral therapy and find a solution to control HIV reservoirs in order to achieve at least a functional cure to HIV infection. This session will look at the immunopathogenesis of HIV persistence, innate and adaptive immune control of HIV reservoirs and strategies based on drug development and/or immune therapies to reduce or eliminate HIV reservoirs. The session will also look at which new tools and technologies have to be developed to measure HIV DNA in vivo and will highlight ethical questions linked to novel clinical trials.




Presentations in this session:

11:00
Introduction



11:05
WESY0101
Powerpoint
New concept in HIV: HIV immunopathogenesis, treatment and vaccine strategies - report back from pre-conference
Presented by Nicolas Chomont, United States



11:20
Molecular control of HIV-1 postintegration latency: implications for the development of therapeutic strategies
Presented by Carine Van Lint, Belgium



11:35
WESY0103
Powerpoint
Slides with audio
Drug development
Presented by Daria Hazuda, United States



11:50
WESY0104
HIV persistence and innate immune control
Presented by Monsef Benkirane, France



12:05
WESY0105
Powerpoint
Slides with audio
Quantifying the HIV reservoir in vivo: current and future tools
Presented by Joseph Wong, United States



12:20
Questions, answers and conclusion





Powerpoints presentations
New concept in HIV: HIV immunopathogenesis, treatment and vaccine strategies - report back from pre-conference - Nicolas Chomont


Drug development - Daria Hazuda


Quantifying the HIV reservoir in vivo: current and future tools - Joseph Wong



Rapporteur report

Track A report by Christophe Vanpouille


This session was dedicated to HIV persistence and ways to reactivate latent HIV-1 that could lead towards an HIV cure.

First, Dr. Chomont (USA) reported on an affiliated pre-conference meeting “new concepts in HIV immunopathogenesis, treatment and vaccine strategies” organized by Drs. Autran and Schmitz. Dr. Chomont described the sensitivity and precision of current assays to measure latent HIV-1, the 2 mechanisms of HIV persistence (ongoing viral replication or viral production by long lived cells) and the potential cell candidates that could be the source of persistent virus. Finally, he highlighted the VISCONTI patients: five out of 32 patients who received very early and prolonged antiretroviral therapy showed sustained immunovirological control for more than 6 years of treatment discontinuation.

 

Dr. Van Lint (Belgium) addressed the molecular control of HIV-1 postintegration latency and its implication for the development of therapeutic strategies. Emphasizing that HIV-1 post integration latency is a multifactorial phenomenon, she described 5 factors contributing to HIV-1 latency: (i) the site of integration in the host cell genome and the chromatin environment; (ii) the absence of inducible cellular transcription factors, such as NF-kB and NFAT, which are excluded from the nuclei of resting cells; (iii) the chromatin organization of the provirus and the presence of the repressive nucleosome nuc-1; (iv) the epigenetic control of the promoter region (histone post-translational modifications) and (v) the absence of Tat and Tat-associated factors, and the sequestration of P-TEFb in a HEXIM/7SK snRNA-bound inactive form.

 

Dr. Hazuda (USA) addressed the problem of why can’t we cure HIV with ARV drugs trying to answer where is the virus and how is it maintained in the face of “suppressive” therapy? She described a “shock and kill” approach (also known as “induction/eradication”) consisting on the use of small molecule(s) to reactivate latent HIV-1 genomes, purge the reservoir and elicit a “sustained virologic response” in the absence of continued antiretroviral therapy. Using a high thoughput screen assay to look for activators of latent HIV-1 gene expression, Dr. Hazuda reported on a list of few candidate compounds. Finally, she pointed out the lack of animal models to study HIV-1 reservoir.

 

Dr. Benkirane (France) talked about HIV-1 and its persistence and restriction in the host. He emphasized first that HIV-1 latency doesn’t only occur at the transcription level but can be post-transcriptional as well. To fully understand HIV-1 persistence, Dr. Benkirane highlighted that we need to better understand transcription elongation and to have better in vitro and in vivo models in which we could track latently infected cells. Then Dr. Benkirane reported on the identification of SAMDHD1 that restricts HIV-1 in DCs. Vpx induces proteasomal degradation of SAMHD1, rendering DCs sensitive to HIV-1.

 

Finally Dr. Wong (USA) described the current and future tools to quantify HIV reservoir in vivo. For many questions, total HIV DNA, residual plasma viremia are still powerful tools. Analyzing specific DNA and cell-associated RNA forms can provide additional information about different forms of persistence and how they respond to interventions. Dr. Wong concluded that all assays to measure HIV-1 persistence are bulk assays. An assay that will address what happens at the cell level is critically needed.




   

    The organizers reserve the right to amend the programme.


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