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4. Title Box “Towards an HIV Cure”: Presentation Outline -Why do we need a cure? -Is a cure feasible and what type of cure can we reach? -Why does HAART fail to cure and what are the mechanisms for HIV persistence during HAART? -How can we cure HIV?

5. “The journey of a thousand miles begins with one step” Lao Tzu

6. Title Box “Towards an HIV Cure”: Presentation Outline -Why do we need a cure? -Is a cure feasible and what type of cure can we reach? -Why does HAART fail to cure and what are the mechanisms for HIV persistence during HAART? -How can we cure HIV?

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12. Title Box Chronic Immune Activation

13. Title Box -Why do we need a cure? -Is a cure feasible and what type of cure can we reach? -Why does HAART fail to cure and what are the mechanisms for HIV persistence during HAART? -How can we cure HIV?

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15. Title Box A Roadmap to an HIV Cure

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18. What Have We Learned from Δ32/Δ32 stem cell transplantation? -HIV infection is critically dependent on CCR5 -HIV persistence is critically dependent on CCR5 -The role of tissues not derived from bone marrow in persistence and infection is in question But… n=1!

19. What Have We Learned from the Elite Controllers? -Defined by the ability to spontaneously suppress plasma viremia -Occurs in less than 1% of HIV-infected individuals -Elevated CD4 cell counts, stable CD4 trajectories, and more favorable clinical outcomes -Overrepresentation of protective HLA alleles -Other mechanisms under active study -Immune Control of HIV infection is possible!

20. Title Box -Why do we need a cure? -Is a cure feasible and what type of cure can we reach? -Why does HAART fail to cure and what are the mechanisms for HIV persistence during HAART? -How can we cure HIV?

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23. HIV Latency in CD4+ T cells - CD4+ T cell latency is established at the transcriptional level predominantly in central memory T cells -CD4+ T cell latency is rare (1/105-106 resting CD4 T cells) -Sequence of latent proviruses does not evolve, suggesting no or low ongoing viral replication. -Patients successfully treated with HAART for longer than 10 years exhibit no appreciable decrease in the size of the latent reservoir.

24. Title Box ? ? ? ? Disulfiram

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26. HIV Latency at the Molecular Level

27. HIV Latency at the Molecular Level

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29. HIV Latency at the Molecular Level

30. HIV Latency at the Molecular Level

31. HIV Latency at the Molecular Level

32. HIV Latency at the Molecular Level

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35. Title Box -Why do we need a cure? -Is a cure feasible and what type of cure can we reach? -Why does HAART fail to cure and what are the mechanisms for HIV persistence during HAART? -How can we cure HIV?

36. Title Box A Roadmap to an HIV Cure

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38. Title Box Jon Cohen, Science 2011;332:784

39. IAS International Working Group

40. Carine Van Lint Stephane Emiliiani Melanie Ott Albert Jordan Dwayne Bisgrove Tokameh Mahmoudi Maribel Parra Shweta Hakre Leonard Chavez Kotaro Shirakawa Vincenzo Calvanese Brigitte Autran Francoise Barre-Sinoussi Monsef Benkirane Nicolas Chomont Tae-Wook Chun Sharon Lewin Christine Rouzious Didier Trono

41. Title Box Science 2010;329:174

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