Towards an HIV Cure: the Scientific Strategy is Launched
The 2012 "Towards an HIV Cure Symposium" took place at the Ronald Regan building in Washington DC on July 20-21, 2012 just prior the opening of the XIX International AIDS Conference. "The strategy is the result of a collaborative effort which has produced a roadmap that will constructively move HIV Cure research forward," said Francoise Barre-Sinoussi, the co-discoverer of HIV, Director of the Regulation of Retroviral Infections Unit at the Institut Pasteur in Paris and the IAS President-Elect. Barre-Sinoussi, together with Professor Steven Deeks, Professor of Medicine at the University of California, San Francisco, is co-chair of the group of 34 leading HIV scientists and clinicians who have developed the Global Scientific Strategy.
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first day of the symposium was opened by a lecture from Antony Fauci who reminded that 2 goals still have to be achieved in the battle against HIV: finding a vaccine and finding a cure.
Professor Fauci pointed out that the NIAID/NIH have decided to invest 70 million USD in the search of an HIV cure within the next 5 years.
Together with Professor Jean-François Delfraissy, Director of the French Agency for AIDS Research (ANRS), Professor Fauci will sign a common commitment letter on Monday 23 July towards a closer collaboration between USA and France in the serach of a cure.
Then the stage was left to Professor Robert Siliciano from Baltimore who developped recently published data of his group on the fact that even if HIV is reactivated from latency, cells do not die due to an insufficient or impaired immune response (Shan L et al. Immunity. 2012 Mar 23;36(3):491-501. Epub 2012 Mar 8.).
Siliciano then addressed the issue of what assay should be used to monitor reservoir eradication.
He showed that there is no correlation between proviral DNA and residual replication competent HIV, proviral DNA being 300 fold more frequent than replication competent virus.
Showing elegantly clonal analysis of these proviruses, he demonstrated that 53.6 percent of them exhibited deletions, 26.3 percent were hypermutated, although only 16.8 persent were intact genomes.
Consequently, the number of clinically relevant infected cells may be 50 fold higher than estimates on coculture assays.
Session 1 was dedicated to the cellular and viral mechanisms that maintain HIV persistence. Warner Greene, Director of the Gladstone Institute of Virology and immunology gave an overview of the mechanisms involved, in particular new Tat complexes.
Session 2 was dedicated to the tissue and cellular sources of persistent HIV on c-ART. Janice Clement from Johns Hopkins pointed out the fact that other cells than CD4+ T cells are important in HIV persistence, in particular monocytes and, to a greater extend macrophages. in an SIV model, lymph nodes and spleen are large reservoirs of persistent viruses. She obtained microglia from animals and cultured it with CEMX174 cells and TNF-alpha. After 14 days, she was able to demonstrate the persistence of replication competent virus with an estimation of 1/5,000 to 1/50,000 microglia infected cell in suppressed animals.
In the same session an abstract presentation was particularly interesting from Sharon Lewin group in Australia. The author, Dr Kumar, received at the end of the symposium the IAS/ANRS award for HIV cure research. Her data showed the role of myeloid dendritic cells in the establishment of HIV latency in resting T cells.
Finally, Maria Buzon from Boston presented interesting data showing that T stem cell memory (TSCM) are in vivo reservoirs for HIV. These cells are even more susceptible in vitro than CD4+ T cells to HIV infection. She also demonstrated that there is an increased contribution over time of these TSCM to the reservoir (from 13 to 28 percent over a decade).
Session 3 was devoted to the origins and the role of immune activation in HIV persistence with an overview given by Daniel Douek. He showed the two aspects of inflammation and the vicious cycles it creates in HIV infection. In particular, Douek reminded that hs-CRP, D-Dimers, IL-6 were predictors of AIDS and non-AIDS related events in the SMART trials, and that s CD14 levels are an independent marker of death in HIV disease. During c-ART, immune activation persists, in particular in tissues, contributing to low thymic outpout, lymphoid tissue fibrosis, poor immune reconstitution, T/B cell dysfunction and mucosal damage.
Key words: Françoise barre-sinoussi, HIV curative strategies., HIV cure, HIV eradication, HIV reservoirs, IAS, Towards HIV cure, towards an HIV cure